TINKLE TONIC - PROTECT THE JEWELS & THE PLUMBING PROSTATE & URINARY SUPPORT * (Cat’s Claw Extract, Non-GMO Pollen, Annatto, Zinc Sulphate) 60 tabs / 500 mg Adult Dog & Cat (* as indicated by a holistic veterinarian) Research Our pet’s bodies are comprised of a complicated and interdependent set of systems in which one organ or system affects another. Attention given to whole body support is essential when treating dysfunction or disease in the kidneys, liver, bladder, digestive, reproductive or urinary tract. Whole food nutrients and plant botanicals can restore imbalance and rehabilitation to the digestive, renal, hepatic, metabolic, endocrine, and urinary systems. The metabolic system is complex and inter-related to other organs, such as the thyroid, liver, kidneys, and pancreas. The endocrine system has an interesting web of interactions with different organs in the body, and helps to regulate the organs which secrete hormones, including the pituitary and adrenal glands, the pancreas, and the testes, to increase testosterone levels and balance hormone levels, and to support the central nervous, digestive, immune and reproductive systems. TINKLE TONIC is a proprietary blended formula of nutrient-dense rain forest botanicals used holistically by veterinarians as a dietary supplement to treat prostate disorders, to support urinary tract and prostate health in canines and felines, to reduce prostrate symptoms including Prostatitis and BHP disease (Benign Hyperplasia Prostate); to promote prostate gland health, to promote healthy bladder, urinary tract and bowel movements, including to reduce swollen and enlarged prostrate glands, to promote strong and healthy urine flow, to relieve pain, discomfort and difficulty when urinating; for incomplete urination, increased frequency of urination or reduction in the volume of urine, to relieve painful and strained defecation, to increase circulation and to strengthen the immune system. TINKLE TONIC is also used by holistic veterinarians to help control urinary infections, to reduce inflammation in the genital-urinary tract, for the treament of bladder and kidney infections, for frequent urination (pollakiruia), straining to urinate (dysuria), blood in the urine (hematuria); for kidney and bladder stones including calcium oxalate stones, struvite stones, uric acid stones, cystine stones, calcium phosphate stones, silica stones; for liver, bladder and kidney diseases, cataracts, constipation, cystitis, obesity, renal insufficiency and to eliminate uric acid. Also used holistically for Feline Lower Urinary Tract Disease (FLUTD), formerly called (FUS), Feline Urological Syndrome, Inflammatory Bowel Disease (IBD or diarrhea), urinary incontinence, Leaky Gut Syndrome, Intestinal Dysbiosis and Intestinal Hypermerability, Inflammatory Digestive Issues including salivary glands, esophagus, stomach and intestines and adjunctively for bladder cancer. 2B TINKLE TONIC is used primarily holistically and effectively to treat prostate disorders. The prostate is a small gland specific to males, located beneath the urinary bladder and wrapped around the urethra. It is made of two lobes that are surrounded by an outer tissue layer. The main function of the prostate is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that, along with spermatozoa, constitutes semen. The rest of the seminal fluid is produced by the two seminal vesicles. The prostate also contains smooth muscles that help expel semen during ejaculation. 23B With the process of aging, it is common for the prostate gland to become enlarged, particularly for mature dogs over the age of 8 years old. As the prostate enlarges, the layer of tissue surrounding the prostate ceases to expand, causing the prostate gland to press against the urethra like a clamp on a hose. The bladder wall becomes thicker and may begin to contract even when it contains small amounts of urine, leading to more frequent urination and possibly urinary continence. 24B TINKLE TONIC has an impressive traditional record of use as a tonic for male dogs over the age of 8 to assist in the optimal maintenance of prostate health. While cats are less likely to suffer from prostate dysfunction in comparison to dogs, it does occur and Tinkle Tonic is effective for cats and dogs. 25B Debate surrounds the pros and cons of spaying and neutering our dogs and cats. While neutering may assist with the control and prevention of prostate problems in pets, many owners are averse to such an action. TINKLE TONIC can be viewed as a therapeutic option for those who do not select to spay or neuter their pets but are dedicated to supporting optimal prostate and urinary support. Regardless of your position as a pet owner, herbs and other supplements may have a prominent place in maintaining the health and wellness of your pet. 26B The plant botanicals and chemicals found in TINKLE TONIC have been used traditionally in medical systems worldwide to support the healthy functioning of the prostate and male reproductive system, while also acting as immune system tonics. Recently, modern science has confirmed the traditional use of the plants found in Tinkle Tonic. Clinical studies have demonstrated the efficacy of herbs to not only treat prostate dysfunction, but also to promote general prostate health and wellness preventatively. Maintaining a proper diet and exercise is critical for the healthy support of the prostate. A diet rich in vegetables, fruit, beans, fish and essential fatty acids is integral to supporting proper prostate function, healthy circulation and a healthy immune system, all which impact prostate health. 27B 28B MEET THE PLANTS OF TINKLE TONIC! 29B Cat’s Claw Extract is used holistically and traditionally as a concentrated immune stimulant, antiinflammatory and antiviral, for its positive effect on sperm motility, for its carragenine and glycoside antiinflammatory content that are used for prostate dysfunction and inflammation, including Prostatitis and BHP as well as to reduce inflammation in the uro-genital tract, to boost energy, to invigorate the body and to enhance infection killer cells, to protect against invasion by potential allergens, pathogens, infections and dermal support, to holistically treat and reduce seasonal and chronic allergies, skin rashes and to reduce the mechanisms that trigger contact allergies, inflammation and swelling including hot spots, hair loss, itching, geriatria (dull coat, lethargy), for most types of viral and bacterial diseases, for all types of inflammation and auto immune diseases and most types of infections. 30B 2 Pollen is used traditionally as a dietary supplement, as an immune stimulant, to rejuvenate the adrenal and prostrate glands, to reduce the risk of infection, to increase focus, mental alertness and stamina due to the presence of all essential amino acids required for optimum bodily performance. Annatto is used traditionally as an antiviral, anti-inflammatory and for prostrate inflammation, including Prostatitis, for BHP, for bladder and kidney infections, to promote healthy support of the urinary and genital tracts, to support of the urinary and genital tracts. for bladder (cystitis) and kidney (pyelonephritis) infections, to support long-term bladder and urinary tract health, to improve healthy urine flow and to increase urination, as an anti-inflammatory, antioxidant, anti-bacterial, fungicidal, astringent and diuretic due to plant steroids found in the leaves, and as an alternative to anabolic steroids. Zinc Sulphate is used traditionally to support and strengthen the immune system, for general prostate health, as an antiviral, to support and strengthen the immune system, to affect sperm motility, sperm quality and support healthy sperm count, for libido, for male infertility, for wound healing, for age-related macular degeneration (AMD), to maintain vision, to develop strong muscles, for strong hair and nails, for hair loss, for proper thyroid function, for blood clotting and to combat the common cold. TINKLE TONIC: PLANT IDENTIFICATION Family: For Cat’s Claw Extract: Rubiaceae For Pollen: Apoidea For Achiote: Bixaceae For Zinc Sulphate: Zingiberaceae Genus: For Cat’s Claw Extract: Uncaria For Pollen: Apis For Achiote: Bixa For Zinc Sulphate: Perichaeta Species: For Cat’s Claw Extract: tomentosa For Pollen: mellifera For Achiote: orellana For Zinc Sulphate: opisthorchis Common Names: For Cat’s Claw Extract: Cat's Claw, Uña de Gato, paraguayo, garabato, garbato casha, samento, toroñ, tambor huasca, uña huasca, uña de gavilan, hawk's claw, saventaro For Pollen: buckwheat pollen, pine pollen, pu huang, polen, pollen, pollin, pawlin, paulin, pawling, poulin For Achiote: achiote, achiotec, achiotl, achote, annatto, urucu, beninoki, bija, eroya, jafara, kasujmba-kelling, kham thai, onoto, orleanstrauch, orucu-axiote, rocou, roucou, ruku, roucouyer, unane, uruku, urucum, urucu-üva For Zinc Sulphate: zinc sulfate, monohydrate, zinc sulfide, white vitriol, zinc sulphate crystals, yellow prussiate of potash Parts Used: For Cat’s Claw Extract: vine bark, root For Pollen: pollen (from flower pollen and nectar) For Achiote: seeds, leaves, bark, roots, shoots For Zinc Sulphate: chemical compound of zinc sulphate 3 Some ways TINKLE TONIC may be used to benefit animal wellness: 60B Bladder Cancer commonly occurs in older dogs and rarely in older cats. The tumor most commonly affecting the bladder is transitional cell carcinoma. Clinical signs of bladder cancer include increased frequency of urination, painful urination or a burning sensation during urination, excessive licking at the genitals and occasionally blood in the urine. Increased thirst, increased volume of urine, and urinary incontinence are rarely associated with bladder cancer and are more typical of kidney disease and diabetes. However, some dogs with bladder cancer can exhibit urinary incontinence. A new test is available to screen dogs for bladder cancer. 61B Studies have shown the benefits of dietary therapy when combined with conventional therapies in dogs with lymphoma, in particular, some herbal supplementation has been shown to limit metastasis and slow irregular cell growth. Since the diet is designed to reduce the growth and spread of cancer, it is often recommended for dogs and cats with any type of cancerous disease. Several metabolic derangements are common in cancer patients. First, they often experience hyperlactatemia (increased lactic acid in the blood). Second, since metabolism of simple carbohydrates produces lactate, a diet with minimum of these carbohydrates might be recommended. Third, weight loss often occurs in cancer patients as a result of cachexia (wasting). Most of the weight loss seen in cancer patients occurs as a result of depleted body fat stores. Dogs with lymphoma who were fed diets high in fat had longer remission periods than dogs fed carbohydrate diets only. 62B Supplements that function as antioxidants and that are recommended for bladder cancer patients, such as vitamins and minerals include vitamin A, C, E, selenium, manganese, zinc and acetyl L found in Super Model in a Bottle; I Feel Good, Get Well Soon and The Daily Paws; Hepa Protect for its Bilberry, burdock and Dandelion Root content; Tinkle Tonic; Easy Flow for its Hawthorn content; I AM A Rock Star and Grape Seed Extract found in I Want Liquid Immunity. 63B Also recommended are Proanthocyanidins, a class of bioflavonoids, for optimal pet health, used primarily for their antioxidant effects against lipid (fat) peroxidation as well as Yelp for Kelp; Gland Candy; All Shins & Grins and Joint Ease for Omega 3 Fatty Acids. 64B Bladder Infections usually occur as bacteria living in and around the lower urinary tract move up the urinary tract through the urethra and infect a normally sterile bladder. Clinical signs of bladder infections or bladder stones are similar and include increased urination frequency, painful urination, a burning sensation while urinating, excessive licking at the genitals and occasionally blood in the urine. Uncommon symptoms include increased thirst, increased volume of urine and urinary incontinence are typically not associated with bladder infections but rather kidney disease or diabetes. 65B A natural diet is recommended to control struvite bladder stones in dogs and cats as well to deal with chronic bladder infections. Recommended holistic products include Yummy Tummy, Stix & Stones, Break It Up; Tinkle Tonic, The Daily Paws, I’m Allergic to Needles, Baby Love Bits and Hepa Protect, and I Cell-Ebrate Life and I Want Liquid Immunity. 6B Bladder and Kidney Stones form as microscopic crystals precipitate out into the urine as microscopic crystals and form small grains of sand-like material. Once the grains develop, additional precipitation can lead crystals to adhere together, creating one or more stones, which can form in the kidney (upper urinary tract) or bladder (lower urinary tract). Clinical signs of bladder stones are similar to those seen in dogs and cats with other disorders of the bladder and include increased frequency or urination, painful urination or a burning sensation during urination, excessive licking at the genitals and occasionally blood in the urine. Uncommon symptoms include increased thirst, increased volume of urine and urinary incontinence are typically not associated with bladder infections but rather kidney disease or diabetes. 67B 4 In dogs, stones are usually associated with infections, as the infection provides a locus for stone formation. In cats, stones are rarely seen with infections. Several different types of stones can occur in the bladder and urinary systems of cats and dogs. Calcium oxalate stones and struvite stones are the two most common types of bladder stones found in the urinary tract. Struvite stones are composed of magnesium, ammonium and phosphate and are typically easier to diagnose. Break It Up is recommended for struvite stones. Stix & Stones can also be added for additional stone protection, as both plant based products offer both preventative and repairative components. Calcium oxalate stones are composed of calcium and oxalate, and are more difficult to diagnose. Studies have shown that dogs that have undergone surgery for calcium oxalate stones will develop new stones within 3 years, thus, a product that repairs is often critical in this type of stone. Stix & Stones is recommended for calcium oxalate stones. Stix & Stones, especially when combined with Break It Up realizes approximately a 94% success rates in dogs and cats for eliminating all types of stones and gravel, as well as providing a number of benefits to the kidney, gallbladder and bladder. Clinical signs of bladder stones in dogs and cats include frequent urination (pollakiruia), straining to urinate (dysuria), and blood in the urine (hematuria). Radiographs (x rays) of the entire urinary system are taken to determine if stones are present in the kidneys, ureters, bladder (the most common location for urinary stones) or urethra. Not every type of stone is easily visualized on radiographs (struvite stones are easily visualized through) and often another test such as an abdominal ultrasound is needed to allow for a definitive diagnosis. Calcium oxalate stones form in acidic to neutral urine. Calcium oxalate stones are further divided into two types that occur naturally in dogs- calcium oxalate monohydrate and calcium oxalate dehydrate. There are some metabolic diseases that might predispose a dog to creating a calcium oxalate stone. For example, a dog with Cushing's disease will over-produce cortisol (commonly known as cortisone). This hormone increases calcium excretion in urine, and the extra calcium in the urine will promote formation of a stone. Recommended supplements include Break It Up, Stix & Stones, Hepa Protect and I Cell-Ebrate Life. Dogs with a condition called hypercalcemia, the presence of abnormally high levels of calcium in the blood-are more likely to develop these types of stones. Hypercalcemia is usually the result of excessive bone reabsorption in hyperparathyroidism or excessive bone destruction in older dogs. Certain dog breeds are genetically predisposed to calcium oxalate stones. These include Miniature Schnauzers, Lhasa Apsos, Yorkshire Terriers, Miniature Poodles, Shih Tzus, and Bichon Frises. The condition is more prevalent in male dogs rather than female dogs. The most immediate concern for a dog with bladder stones is that the urinary opening may get obstructed as the dog attempts to pass the stones; this is largely a problem with male dogs, but the results can be life-threatening uremic poisoning. In such cases, the veterinarian will try to dislodge the stone, flushing it back into the bladder to restore the patency of the urinary opening. If the stone cannot be dislodged, a new urinary opening may have to be surgically created. The urethra (the narrow tube connecting the urinary bladder to the outside world) is a difficult place to perform surgery so it is preferable to move the stone back into the bladder for removal rather than attempting removal from the urethra. Bladder stones are irritating to the bladder simply by rubbing on the tender lining. Bleeding typically results and, of course, the chance of developing chronic bladder infections is markedly increased with bladder stones. 5 Prevention of calcium oxalate stones is difficult through dietary modifications alone. A diet that is low in proteins and oxalates and high in magnesium, phosphorous, and calcium is recommended. This works in two ways: 78B Increased magnesium and phosphorous reduces the amount of calcium in the urine. Increased calcium in the diet limits the absorption of oxalates from the intestines. Ingesting potassium citrate helps in preventing calcium oxalate stones, since calcium bonds to citrate creating calcium citrate, a compound that is soluble. This prevents calcium from binding with oxalate to create calcium oxalate, a compound that forms deposits in urine and ultimately results in bladder stones. Potassium citrate also forms a soluble compound with oxalates, reducing acidity in the urine, and is recommended as a preventive measure and treatment. 79B 80B 81B Other types of stones include uric acid stones (Ammonium urate), which are formed from urine with an excessive amount of acid that may be caused by the large amounts of meat consumption. Cystine stones are made of building blocks that make up muscles, nerves, and other parts of the body; this kind of disease is usually inherited. Calcium phosphate stones and silica stones can form but are relatively rare. Urinalysis can indicate the prevalence of stones, and the pH balance gives a hint of the type of stone that can be expected. However, unless the stone is extricated by surgery or forceful expression and examined, there is no surety of the type of stone. Diuretics, especially of the thiazide class, may help in two ways by increasing the amount of urine and reducing the calcium content. 82B In cats, struvite stones most commonly form in the absence of a bladder infection, unlike dogs, in which a bladder infection usually initiates the formation of stones. 83B In cats, crystals, stones and the condition called feline lower urinary tract disease (FLUTD), most commonly form in cats which are fed dry commercial foods that are higher in vegetable materials and grains rather than meat based diets, which should be fed to cats as obligate carnivores. Recommended supplements include omega 3 fatty acids such as Gland Candy, Yelp for Kelp, The Daily Paws, antioxidants such as All Shins & Grins and Hepa Protect for its dandelion and horsetail content. An recommended adjunctive product is Tinkle Tonic. 84B Vitamin C has been used with varying degrees of success in helping prevent the formation of some bladder stones in cats and dogs. Greater success for combating stones is acheived by using Stix & Stones or Break It Up, which realizes approximately a 94% success rates in dogs and cats for eliminating all types of stones and gravel, as well as providing a number of benefits to the kidney, gallbladder and bladder. Noni is helpful in creating acidic urine, which can help discourage the creation of most types of stone. Noni has been beneficial as an antioxidant supplement for dogs and cats suffering from allergies or skin problems, immune disorders, respiratory or cardiovascular diseases, eye disorders such as failing vision or cataracts, or general problems associated with aging. It is especially beneficial to aging animals, and animals with heart disease, cancer and atopic dermatitis. Additionally, Noni is used a vitamin C supplement used in growing, pregnant, lactating, stressed, and working pets with no concern for toxicity. Noni is found in I CellEbrate Life and I Want Liquid Immunity. 85B 86B 87B Cataracts are a common eye disorder of older dogs and rarely among cats. While cataracts can occur as a secondary disease of diabetes, it can also occur in young pets as a congenital problem. Cataracts are classified as an opacification and calcification of the eye lens. Classification can be mild (immature cataracts) with minimal affect on vision or severe (mature to hypermature cataracts) that cause blindness. The condition of cataracts is not to be confused with nuclear sclerosis, which is when the lens becomes cloudy but does not interfere with vision. 8B Research exists that use of Vitamin C may be useful for cataracts due to its content of Proanthyocyadins. Principle recommendations for treatment include use of antioxidants All Shins & Grins; I Feel Good and I Want 89B 6 Liquid Immunity and specific vitamins and minerals that prevent oxidation of healthy cells and which encourage free radical scavenging, which creates toxic by-products in the body. Recommended supplements include vitamins found in All Shins & Grins and I Want Liquid Immunity are C and E, selenium, manganese, zinc, bilberry, grape seed extract and proanthyocyadins. Tinkle Tonic is also recommended for Macular Degeneration. Hepa Protect contains bilberry, is also recommended for eye disorders, including cataracts and macular degeneration, due to its antioxidant effects. Its flavonoid compounds (anthocyanosides) are the most pharmacologically active. These flavonoids have several effects: first, improving capillary strength (vitamin C) decreased platelet clumping, lowering of blood sugar (useful for diabetic pets) and protective effects against gastric ulcers (due to increased mucous production). Bilberry’s anthocyanosides have a special attraction to the retina, which may explain the herbs usefulness in eye disorders. Tinkle Tonic is also recommended for its effects to counter the progression of Macular Degeneration. Hepa Protect contains bilberry which is used commonly in Europe and Central and South America for people and pets for the treatment of poor night vision and day blindness. Regular use of bilberry is also thought to help prevent or treat other eye disorders such as macular degeneration, diabetic retinopathy and cataracts. In pets, bilberry can be used for cataracts and is recommended to be used in combination with Vitamin E. There are no known drug interactions and bilberry is considered safe. Dogs can produce vitamin C in their bodies, and because of this ability, nutritionists have long considered it unnecessary to add C to a dog’s diet. Until recently, few dog food makers added vitamin C to their products or if it was added, it was for the preservative action of the vitamin, rather than its nutritive value. According to the Whole Dog Journal, researchers and Vitamin C advocates have since discovered that young dogs and cats who regularly receive C supplements develop fewer cases of hip dysplasia and arthritis. Stress is the best-known cause of vitamin C depletion in dogs and cats. Physical stress comes in many forms: gestation, lactation, growth, hard work (dogs used for herding, hunting, tracking, etc.), vaccinations, injuries, tail-docking or ear cropping, or illness. Emotional stress, whether caused by relocation, weaning, or demanding training, can also deplete this reserve. In fact, researchers can measure the level of stress a dog experiences by measuring the degree of depletion of the vitamin in the dog’s blood. Conversely, many studies have found that dogs (as well as humans) that are supplemented with vitamin C show greater resistance to disease, and a better ability to recover from injuries or illness. Constipation is a common problem in dogs and cats which is often suspected by owners but rarely diagnosed. Constipation occurs when a pet is unable to fully evacuate the bowels. Feces remains in the colon where water from the fecal matter continues to be absorbed and when the fecal matter dries out and forms a hard mass. In dogs, constipation generally occurs when a large content of foreign material is consumed. True constipation regularly can occur in cats. Cats can develop an unusual form of constipation or obstipation (severe constipation) called megacolon. The cause is unknown but over time, the colon loses its ability to contract and void feces. Recommended treatments include Shake Ur Groove Thing; Tinkle Tonic; Hepa Protect, and I Want Liquid Immunity. Dietary changes can also be made concurrently, including preparing salmon, long grain cooked rice with a small amount of sale (1/4 teaspoon) and taurine. Feline Lower Urinary Tract Disease (FLUTD), formerly called FUS, (feline urological syndrome) is the most commonly diagnosed disorder of the bladder in cats. Clinical signs present as increased urination, painful 7 urination or a burning sensation during urination, excessive licking at the genitals, and occasionally blood in the urine. Owners commonly assume that their cats are constipated as their pets spend a lot of time in the litter box trying to eliminate. Increased thirst, increased volume of urine and urinary incontinence are rarely associated with bladder disease and are more commonly associated with kidney disease and diabetes. FLUTD is a common problem in cats of any age, usually resulting from struvite crystals (and may form struvite stones) that form in urine with an alkaline or high pH, which irritates the bladder. Cats can also have FLUTD without the presence of crystals and can also have a low pH urine level. About 25% of cats are predisposed to FLUTD due to an abnormal pouch located at the end of their bladder, called vesicourachal diverticulum. 10B FLUTD can affect male and female cats, typically between 2 and 6 years of age, although struvite stones are most commonly seen in female cats between 1 and 2 years of age. Male cats are more likely to develop an obstruction of the urethra due to their anatomy. 10B The cause of FLUTD is unknown although some holistic vets attribute the condition to eating dry foods which generally contain more minerals such as magnesium, and predispose the cat to the condition. Also, decreased water intake and decreased urination may predispose the cat to FLUTD. While magnesium may be related, it appears that the pH level of urine has more influence on the development of crystals, often seen in cats with FLUTD. 102B In dogs, the desire to acidify the urine through prescription-driven diets has led to an increase in oxalate stones in the bladder, a type of stone which is more commonly experienced with acid urine (acidic urine=oxalate stones and crystals), whereas alkaline urine=struvite stones or crystals. The upside to alkaline urine is a greater likelihood of diagnosis. 103B In cats, crystals, stones and the condition called feline lower urinary tract disease (FLUTD), most commonly form in cats which are fed dry commercial foods that are higher in vegetable materials and grains rather than meat based diets, which should be fed to cats as obligate carnivores. 104B Natural treatments include cranberry as it makes the urine more acidic. Also recommended are Stix & N Stones, Yummy Tummy Annatto, Tinkle Tonic and Break It Up for their ability to normalize and balance acidic urine level. 105B Other recommended supplements include omega 3 fatty acids such as Gland Candy, Joint Ease, The Daily Paws, and I’m Allergic To Needles;, vitamin E, and antioxidants such as All Shins & Grins and I Want Liquid Immunity. Hepa Protect for its dandelion and horsetail content. 106B Serenity Zen Dog & Cat or Soothed & Serene can be added to relax all bodily systems and support urinary, digestive and endocrine function. Since urinary tract infections are caused by bacteria such as E. coli which function in alkaline urine, cranberry supplementation may return pH levels to balance. There is some disagreement between causal and balancing factors of pH levels, however, pure cranberry juice (not sugary, from concentrate) seems to be most effective, administered between 8 to 16 ounces per day. For cranberry extract tablets or capsules, a daily dose of 250 mg is recommended. 107B Inflammatory Bowel Disease (IBD or diarrhea) is a name given to a group of conditions that are characterized by pathologic evidence of inflammation of the intestinal tract which is associated with chronic and persistent gastrointestinal signs. IBD can present in both dogs and cats at all life stages. 108B Clinical signs often reflect the location of the intestinal lesions (inflammation) and include vomiting, diarrhea and weight loss. Lesions of the upper GI tract (gastrointestinal tract involving stomach and upper small 109B 8 intestine) usually include vomiting, whereas lesions of the lower small intestinal tract and colon more commonly cause diarrhea. Causes of IBD are numerous and include parasites (whipworms, giardia), fungi (histoplasmosis, protothecosis), bacteria (Salmonella, Campylobacter, pathogenic E. coli), food allergy/hypersensitivity, cancer (lymphosarcome, adenocarinoma), and idiopathic causes such as eosinophilic, lymphoctic-plastmacytic or glanulomatous. Most commonly the idiopathic classification of IBD is seen in dogs and cats. Most vets suspect autoimmune failure as the leading cause of the disease as well as allergy and sensitivity to diet. Recommended supplements include Yummy Tummy, The Daily Paws, I Feel Good, Joint Ease, Soothed & Serene and Love Your Liver. Leaky Gut Syndrome, Intestinal Dysbiosis and Intestinal Hypermerability are conditions in which people and pets have whole proteins which lead through the wall of the digestive tract due to a hyperpermeable condition and enter the blood, causing allergic reactions. These reactions may include food allergies, arthritis, autoimmune diseases, impaired nutrient absorption and chemical sensitivities. It has been theorized by vets that many chronic diseases treated over the years may actually result from leaky gut syndrome. The most commonly cited potential cause for leaky gut syndrome may be Candida albicans, a form of yeast that enters the bloodstream from the intestinal tract and may cause chronic allergies. Overgrowth of this yeast and other organisms may occur in pets with chronic intestinal disease and in pets which are prescribed chronic antibiotic or NSAID therapies. The organisms can produce toxins that cause leaky gut syndrome and the increased permeability may allow greater absorption of toxins, causing more harm. Inflammatory bowel disease (IBD) and “leaky gut” have received recent notoriety, likely due to the high amount of diagnosed cases. Many holistic practitioners believe the increase in diagnosis is a direct result of drastic changes made to dog’s and cat’s diets over the past 50 years. Both of these diseases involve a compromised immune system that in turn, creates a chronic dysbiosis in the gut. In healthy digestion, proteins are broken down into amino acids that can be absorbed into the bloodstream and large particles of protein are held in the lumen of the gut until they can be fully digested. With the leaky gut syndrome, the cells of the gut wall loosen their normally tight attachments, and food proteins are absorbed before they are fully broken down. The body’s immune system regards these proteins suspiciously, and classifies them as foreign invaders, inciting the immune system, which produces inflammation and causes the body to react to fend off the “invaders.” Leaky gut syndrome can be instigated by a number of factors: food allergies, Candida overgrowth (most often from excessive antibiotic or steroid use), or stress. Symptoms can be highly variable; many chronic diseases such as arthritis, skin and other allergic disorders, and fatigue and malaise have been attributed to a leaky gut. Inflammatory bowel disease (IBD) is also due to an immune system gone awry. IBD has many of the same symptoms as leaky gut, with perhaps a more profound immune system response. Either of these diseases may predispose the patient to the other disease, and both can become chronic. Conventional treatments for leaky gut and IBD include antibiotics, and interestingly, steroids or other drugs that shut down the immune system. Holistic practitioners, in contrast, will try to balance the immune function of the digestive system by encouraging normal flora and boosting immunity by recommending herbal treatments that promote healthy gut flora, typically an herb that contains Prebiotics, Probiotics and FOS, as well as acupuncture. Recommended supplements include Yummy Tummy, I Feel Good, Love Your Liver and Joint Ease. 9 A common misconception when treating either IBD or leaky gut is that you can effect a cure simply by changing the diet of your dog and cat from beef to an exotic protein source, such as kangaroo or ostrich. While diet changes may be effective for the short term, an unhealthy digestive tract will eventually react to, and may become allergic to, whatever protein it is exposed to most. Long-term healing will always rely on returning the gut to health. Re-establishing a healthy, more natural gut microflora is the one necessary step common to all cases of dysbiosis. 120B Inflammatory Digestive Issues: There are many common diseases and conditions of the digestive tract found in dogs and cats including the following: 12B 12B Salivary glands These glands are not a common site for disease, but they can be affected by inflammation that is either primary or that occurs as a consequence of other diseases such as distemper or other viruses. Trauma may produce swelling, which typically goes away on its own. Sometimes, after trauma or foreign body penetration, one of the dog’s or cat’s glands fills with mucous and saliva, producing a dramatic swelling that needs to be drained surgically. Tumors of salivary glands do occur, but they are rare. 123B Esophagus There are several rather uncommon abnormalities of the esophagus, including esophageal dilatation, idiopathic mega-esophagus, and esophageal stenosis/stricture. Symptoms of these diseases may vary, making accurate diagnosis difficult; surgery may be indicated for severe conditions. Some cases may respond to diet changes and/or alternative treatments. 124B 125B Inflammation of the esophagus is frequently due to gastric reflux (often from persistent vomiting), but it may also be instigated by anesthesia or other drugs. Conventional Western medicine will treat severe cases with antibiotics, steroids, and drugs to stop the vomiting. Alternative practitioners will likely recommend herbs such as Yummy Tummy or I Feel Good (Cat’s Claw Extract) to soothe the tissues and for their natural antibiotic and immune-enhancing activities. 126B Stomach and intestines Gastritis (inflammation of stomach) and enteritis (inflammation of the intestines) offer panoply of diseases, caused by the usual culprits: bacterial, viral, fungal, protozoal, traumatic, and neoplastic diseases. For the holistic practitioner, almost all these can be lumped under the general term “dysbiosis” (from two Greek terms “dys,” meaning bad, abnormal, or difficult; and “bios,” meaning life or living organisms). The term seems to fit almost all the digestive problems seen in dogs and commonly in cats. 127B Of special interest are viral disease complexes that affect the intestines, including parvovirus, distemper, and corona viral gastroenteritis – highly contagious diseases that can be severe, especially in puppies. Symptoms vary with the disease and its severity, but typically include diarrhea (possibly severe) and perhaps vomiting. 128B The large intestines can also be infected, although rarely, with a myriad of microorganisms, parasites, and mechanical disorders. The most common symptom is diarrhea. Conventional Western medicine uses a variety of drugs to control the diarrhea; holistic treatment concentrates on returning the bowel micro flora to normal using an herbal such as Yummy Tummy to restore intestinal flora. 129B Primary natural treatments include detoxification therapies, such as Yummy Tummy and Shake Ur Groove Thing, which are capable of killing Candida albicans in some pets, along with I Feel Good and Tinkle Tonic. Glutamine, an amino acid, found in Joint Ease Super Dog & Cat (plus it contains glucosamine and MSM); Don’t Go Breaking My Heart for its polyphenol content, for its role it plays in the health of the digestive tract, muscle cells and immune system. 130B 10 Antioxidants are also recommended, including vitamin A, E and selenium as well as Prebiotics and Probitotics which encourage digestion and healthy gut balance such as found in I’m Allergic to Needles, Joint Ease and Baby Love Bits. Plant enzymes may also be recommended to promote health cellular processes, digestion and absorption of nutrients. Other treatments include omega-3 fatty acids such as Yelp for Kelp, Glandy Candy, Joint Ease and Life’s An Itch. Kidney Disease involves any trauma to the kidneys and prolonged trauma can lead to kidney failure. Kidney failure can occur in dogs and cats of any age and for a variety of reasons, including low blood pressure and low blood volume, heart failure and medications such as NSAID’s and ACE inhibitors such as enalpril, which is prescribed for heart disease. Renal causes include direct damage to the kidneys, acute kidney failure, toxins such as antifreeze poisoning or aminoglycoside antibiotics, cancer of the kidneys, kidney trauma including kidney stones, congenital disorders (polycystic kidney disease, rental cortical hypoplasia) and infections (leptospirosis in dogs, feline infectious peritonitis in cats). Postrenal causes include a blockage of urine outflow from the kidneys or bladder, acute kidney failure from bladder stones, urethral stones, bladder cancer and feline lower urinary tract disease (FLUTD), including urinary tract obstructions that occur commonly in male cats. Treatment of chronic kidney failure includes dialysis or kidney transplantation. In cases of chronic kidney failure, protein and phosphorous are restricted or limited and a basic diet is encouraged. Easy Flow! is often recommended for pets with heart disease, heartworm disease and kidney disease. The flavonoids appear to decrease the leakiness of the capillaries, improving the cardiac blood flow by dilating coronary arteries and improving the contractility of the heart. Easy Flow! may also be useful in controlling mild heart arrhythmias. It may act by inhibiting the enzyme phophodiesterase or as an ACE inhibitor, making it a possible substitute for drugs susch as enalapril (Enacard.) Doctors have also prescribed hamamelis for pets undergoing chemotherapy, especially for producing cardiac side effects. Supplementation includes a hepaprotective product such as Hepa Protect or Stix & Stones; I Feel Good combined with adjunctive glandular therapies such as I AM A Rock Star or Dog & Cat Kryptonite are effective. Tinkle Tonic can be used adjunctively. Urinary Incontinence is defined as a pet that is unable to completely control its ability to urinate. Urinary incontinence is also referred to as leaky bladder. Clinical sings include “wet spots” where a pet sleeps and dribbled urine as a pet moves around. Urinary incontinence can be identified in pets of all ages, including puppies and kittens but generally affects middle to older aged pets. Pets can become incontinent following spaying or neutering since it often responds to a change in estrogen or testosterone levels, which affects the tone of the urethra and prevents urine leakage. Other hormonal imbalances such as hypothyroidism and occasionally bladder tumors can lead to a leaky bladder. Bladder tumors can cause increased frequency of urination, a burning sensation during urination, excessive licking at the genitals and sometimes blood in the urine. Natural treatments include soy protein found in That’s A Nice Looking Bone, Yummy Tummy; Tinkle Tonic and Stix & Stones, as well as glandular supplementation with I AM A Rock Star or Dog & Cat Kryptonite. The Daily Paws is also recommended after spaying or neutering to tone the urethra and surrounding connective tissue and the phytoestrogens help to establish hormonal balance. 11 TINKLE TONIC: TEST DRIVE WHAT IT CAN DO FOR YOUR PET 14B Main Actions: For Cat’s Claw Extract: immune stimulant, anti-inflammatory, antimutagenic (cellular protector), anticancerous, antiulcerous For Pollen: immune stimulant, to fight infections, to increase focus, for mental alertness for physical stamina For Achiote: antimicrobial, antiseptic, diuretic, as a Probiotic digestive stimulant and for digestive problems associated with heartburn, constipation and stomach ache, to reduce acid, as a liver protector (hepatoprotective), to lower cholesterol (hypocholesterolemic), as an antioxidant, insect repellant, diuretic, for prostrate and urinary infections, for prostatitis, kills bacteria, fights free radicals, kills parasites, kills germs, increases urinations, lowers blood pressure, used as a mild laxative, protects liver, as an anti-rheumatic, anti-inflammatory, to treat bladder and kidney infections and for bacterial infections in the urinary and genital tract cystitis, (bladder infection), and pyelonephritis, (kidney infection) and for some sexually transmitted diseases such as herpes and gonorrhea, for skin care and skin anti-aging (for its antioxidant and ultraviolet ray [UV]-protective effect) For Zinc Sulphate: as a mineral, for sickle cell anemia, for zinc deficiency, for diarrhea, for immune system health, for wound healing, for regulating cell growth, DNA and protein synthesis, for energy metabolism, for regulation of gene transcription, for hormone levels, for growth factor metabolism, for coat health, for wound healing 142B 143B 14B 145B 146B Primary Holistic Uses: For Cat’s Claw Extract: as an immune stimulant, as an adjunctive therapy for cancer (to reduce side effects of chemotherapy and protect cells), as a bowel cleanser and anti-inflammatory for Crohn's, colitis, diverticulitis, irritable bowel syndrome (IBS), and other bowel problems, as an anti-inflammatory for all kind of arthritis and muscle pains, strains and injuries, as a general daily tonic to tone, balance, and strengthen all body functions, for stomach ulcers, for ulcerative colitis and as an ulcer preventative, as a stomach and bowel protector,immune stimulant, anti-inflammatory, antimutagenic (cellular protector), anticancerous, antiulcerous, improving symptoms of both osteoarthritis and rheumatoid arthritis, hemorrhoids,parasites, shingles, bone pains, treat fleas, immune stimulant, anti-inflammatory, antimutagenic (cellular protector), anticancerous, antiulcerous For Pollen: as an immune booster, for energy, as an overall support for geriatrics and young children, to stimulate organs and glands, to enhance vitality For Achiote: reduces inflammation, stops coughing, dries secretions/oils, cleanses blood, soothes membranes, reduces phlegm, used as an expectorant, reduces fever, raises blood sugar, used as a topical antiseptic for ear, eye and skin infections, for digestive problems (heartburn, constipation, stomachache) for prostrate and urinary infections, for hypertension, for high cholesterol levels, for wound healing For Zinc Sulphate: as a dietary supplement, for a healthy immune system, for zinc deficiency, for burnsfor diabetes mellitus, for hemodialysis, for infections, chronic due to increased immune responses, for intestinal diseases (celiac, Crohn's, diarrhea, sprue, for ulcerative colitis), for intestinal parasitism, for malabsorption syndromes associated with pancreatic insufficiency—pancreatic disease, cystic fibrosis, for renal diseases, nephrotic syndrome, renal failure, uremia, for short bowel syndrome, for skin disorders (exfoliative dermatoses), psoriasis, for prolonged stress, for prolonged trauma 147B 148B 149B 150B 15B Properties/Actions Documented by Research: For Cat’s Claw Extract: anti-inflammatory, antiulcerous, anticancerous, antidepressant, antileukemic, antimutagenic (cellular protector), antioxidant, antitumorous, antiviral, contraceptive, immune stimulant For Pollen: anti-bacterial, anti-fungal, antibiotic, alleviate menstrual cramps, to support lost sexual desire and energy, improve fertility in females and males, to speed wound healing, normalize digestive problems, alleviate migraine headaches, relieve prostate problems, reduce cholesterol, improve energy levels, weight control, to build resistance to airborne pollen allergies For Achiote: aldose reductase inhibitor (linked to diabetic complications), antibacterial, antihemorrhagic (reduces bleeding), antivenin 152B 153B 154B 15B 12 For Zinc Sulphate: anti-inflammatory, for wound healing, for bowel inflammatory diseases, for sickle cell anemia, for zinc deficiency, for diarrhea, for immune system health, for wound healing, for energy metabolism Other Properties/Actions Documented by Traditional Use: For Cat’s Claw Extract: analgesic (pain-reliever), anticoagulant (blood thinner), antidysenteric, blood cleanser, detoxifier, diuretic, gastrotonic (tones, balances, strengthens the gastric system), hypocholesterolemic (lowers cholesterol), tonic (tones, balances, strengthens overall body functions), wound healer, fights free radicals, for depression For Pollen: anti-bacterial, anti-fungal, antibiotic, to support lost sexual desire and energy, improve fertility in females and males, speed wound healing, normalize digestive problems, relieve prostate problems, reduce cholesterol, improve energy levels, weight control, to build resistance to airborne pollen allergies, or aging, allergies, amenorrhea (absence of menstruation), antibacterial, antifungal, antioxidant, appetite stimulant, arthritis, benign prostatic hypertrophy (BPH), bleeding, bronchitis, chronic renal insufficiency, colitis, constipation, cough (bloody), diarrhea, diuretic, dysentery (bloody diarrhea), enteritis (inflammation of bowels), growth, hay fever, hemorrhage (cerebral), hemorrhoids, high cholesterol (hyperlipidemia), immunomodulator, infertility, liver dysfunction, nutrition, pregnancy nutritional supplement, prostatitis (inflammation of prostate), radioprotection, renal impairment, rheumatism, sexual performance, skin care, skin eruptions, tonic, vomiting (blood), weight loss, allergies, appetite, asthma, Benign prostatic hypertrophy (BPH), cancer prevention, diabetes, GI disorders, health maintenance, strength and stamina For Achiote: antacid, hypocholesterolemic (lowers cholesterol), anti-inflammatory, antiseptic, aperient (mild laxative), aphrodisiac, astringent, digestive, for blood cleansing, cancer, diabetes, dysentery, fever, kidney problems, parasites, skin disorders, to stop bleeding, and as an aphrodisiac, astringent, dye For Zinc Sulphate: for fur loss, antioxidant, for immune support, for wound healing, digestion, reproduction, physical growth, diabetes control, taste and smell, to support the prostate, to support health sperm count, for bowel inflammatory disorders (colitis, UC, IBS), for benign prostatic hypertrophy (BPH), for constipation, for age-related macular degeneration, for healthy libido, for insulin and male reproductive support, for muscle support, to support health of the retina, bones, skin, kidneys, liver and pancreas, to treat Dermatosis Contraindications: For Cat’s Claw Extract: Do not use if your pet is pregnant or nursing. Contraindicated for pets with leukemia. Consult with your Vet prior to use if your pet is scheduled for surgery, using blood thinners or have an autoimmune disease. Cat's Claw has been clinically documented with immunostimulant effects and is contraindicated before or following any organ or bone marrow transplant or skin graft. Cat's Claw is contraindicated in pets whose owners are seeking to have them bred. There is a concern that cat’s claw might make blood pressure control difficult during surgery. Stop taking cat’s claw at least 2 weeks before a scheduled surgery. For Pollen: Animals with an allergy to bee stings (bee venom), intolerance to honey, or allergy to ragweed/chrysanthemums should avoid bee pollen products. Honey has been known to cause small to severe allergic reactions in animals allergic to bees/pollen. Reaction can include anaphylaxis, an acute allergic response, which may be life threatening. For Achiote: The seed extract was reported to elevate blood sugar levels in dogs, and it is therefore contraindicated for animals with diabetes. For Zinc Sulphate: for gastrointestinal diseases (ulcerative colitis, Crohn’s disease, short bowel syndrome), for malabsorption syndrome, chronic liver disease, chronic renal disease, sickle cell disease, diabetes, malignancy, for vegetarians, for pregnant and lactating animals Drug Interactions: For Cat’s Claw Extract: Cat's Claw may potentiate Coumadin and blood-thinning drugs and medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) as Cat's claw might decrease how quickly the liver breaks down some medications. Some medications changed by the liver include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), and many others. 13 Taking cat's claw along with medication for the liver can increase the effects and side effects. May interact with medications for high blood pressure (Antihypertensive drugs) as Cat's claw may decrease blood pressure and/or cause your blood pressure to go too low. May interact with medications that decrease the immune system (Immunosuppressants) as Cat's claw might increase the immune system, decreasing the effectiveness of medications that suppress the immune system. Before giving cat's claw to your dog/cat, talk to your Vet. For Pollen: Hypersensitivity reaction causing pruritus, headache, swelling, sneezing, anaphylaxis, hypereosinophilia, and eosinophilic gastroenteritis consisting of nausea, abdominal pain, and diarrhea. For Achiote: None reported. For Zinc Sulphate: Zinc may interact with quinolone antibiotics such as Cipro® and tetracycline antibiotics such as Achromycin® and Sumycin®. Zinc can reduce the absorption and action of penicillamine, a drug used to treat rheumatoid arthritis. Zinc may interact with Thiazide diuretics such as chlorthalidone (Hygroton®) and hydrochlorothiazide (Esidrix® and HydroDIURIL®). 169B 170B 17B 172B Cautions: For Cat’s Claw Extract: May cause headache, dizziness, and vomiting. Cat's Claw may reduce platelet aggregation and thin the blood. May lower blood pressure. Use caution if your pet has low blood pressure. Cat’s claw might cause the immune system to become more active, and this could increase the symptoms of autoimmune diseases. If your cat/dog has one of these conditions, consult with your Vet provider. For Pollen: Do not use if your pet has a hypersensitivity or allergy to pollen. Consult with your Vet if your pet is pregnant, nursing, has blood disorders or liver disease. Other potential effects include itching, headaches, inflammation, sneezing, anaphylactic shock, nausea, abdominal pain and diarrhea. For Achiote: It might raise blood sugar levels and may potentiate medications used to treat hypertension. Do not use if your pet is pregnant or nursing. For Zinc Sulphate: None recorded except with zinc-containing nasal gels or sprays can cause long-lasting or permanent loss of smell (anosmia) as well as nausea, stomach upset or heartburn. 173B 174B 175B 176B 17B Suggested Dosage: (please confirm dosage according to life stage of dog or cat ) Dogs & cats up to 12 pounds: ½ capsule, one time daily. Dogs & cats 13-25 pounds: ½ capsule, two times daily. Dogs & cats 26+ pounds: 1 capsule, two times daily. 178B 179B 180B 18B Indications for Use: pets in need of renal support as indicated by BUN, creatinine, phosphorus, urine specific gravity; hepatic patients in need of additional renal support 182B This product contains no animal products, gluten, artificial colors, flavors or preservatives and is not tested on animals. Individual ingredients are well-researched, natural, safe and effective. 183B TINKLE TONIC: ALL SORTS OF INTERESTING FACTS ABOUT HOW THIS PLANT MIGHT BENEFIT PET HEALTH, ITS BIOLOGICAL ACTIVITIES AND STUDIES CONDUCTED 184B CAT’S CLAW EXTRACT: Cat’s Claw Extract is used traditionally to treat asthma, inflammations and infections of the urinary tract, for arthritis, rheumatism and bone pain, as a kidney cleanser, to cure deep wounds, to control inflammation, for gastric ulcers, for gastritis, for diabetes, for asthma, for tumors, and for dermal inflammations. 185B 186B Also used holistically for fevers, abscesses, tumors, and inflammations, for internal cleansing, to tone and cleanse the intestinal tract, as an adjunctive treatment for cancer and AIDS as well as for other diseases that target the immune system, for neuralgia, for sciatic nerve spasm, for chronic inflammation of all kinds, and viral diseases such as herpes zoster (shingles). 187B 14 Dr. Brent Davis, D.C. has written several articles on Cat's Claw and refers to it as the "opener of the way" for its ability to cleanse the entire intestinal tract and its effectiveness in treating stomach and bowel disorders such as Crohn's disease, leaky bowel syndrome, ulcers, gastritis, diverticulitis, and other inflammatory conditions of the bowel, stomach, and intestines. Dr. Julian Whitaker, M.D. reports using Cat's Claw for its immune-stimulating effects, for cancer, to aid in the prevention of strokes and heart attacks, to reduce blood clots, and for diverticulitis and irritable bowel syndrome. Traditional use of Cat's Claw indicates that it has the ability to protect cancer cells from maturing but in order to destroy cancer cells that resistant to prescription medicines, another herb, called graviola, found in Get Well Soon, is recommended. Immune Function Cat's Claw has become popular and renowned in the natural products industry and is used primarily to boost immune function, as an anti-inflammatory, as a general health and wellness tonic and as a preventative to remain healthy. Further, Cat’s Claw is used for arthritis, for bowel and colon problems, and as an alternative and complementary therapy for cancer. Cat’s Claw Extract contains all the natural chemicals that nature provides in the proper ratio (including immune-stimulating alkaloids, anti-inflammatory glycosides, and antioxidant chemicals), without chemical intervention. Anti-Inflammatory A significant area of study has focused on Cat's Claw's anti-inflammatory properties. While plant sterols and antioxidant chemicals found in Cat's claw account for some of these properties, new and novel plant chemicals called quinovic acid glycosides were documented to be the most potent anti-inflammatory constituents of the plant. This study and subsequent ones indicated that Cat's Claw (and, especially, its glycosides) could inhibit inflammation from 46% up to 89% in various in vivo and in vitro tests. The results of these studies validated its long history of indigenous, traditional use for arthritis and rheumatism, as well as for other types of inflammatory stomach and bowel disorders. It was also clinically shown to be effective against stomach ulcers in an in vivo rat study. The bark and root of cat's claw are used to treat different ailments to help reduce inflammation and fight specific viruses. Holistic veterinarians recommend the use of Cat’s Claw (in conjunction with a high dose of Shark Cartilage) to help treat cancer instead of chemotherapy, radiation or surgery. Often times tumors go into long term remission. In general, animals that eventually succumb to cancer, live much longer then expected and usually are more comfortable, without the serious side effects noted with conventional treatment options. Once the cancer goes into remission, it is against medical advice to completely stop the use of Cat’s Claw, as the cancer may come back. Instead, cut down the dosage and continue having the animal take Cat’s Claw In addition to the immunostimulant alkaloids, Cat's Claw contains the alkaloids rhynchophylline, hirsutine, and mitraphylline, which have demonstrated hypotensive and vasodilating properties. The rhynchophylline alkaloid has shown to prevent blood clots in blood vessels, dilate peripheral blood vessels, lower the heart rate, and lower blood levels of cholesterol. Some of the newer research indicates that Cat's Claw might be helpful to people with Alzheimer's disease, which could be attributable to the antioxidant effects already confirmed or, possibly, to the dilation of peripheral blood vessels in the brain by alkaloids such as rhynchophylline. Another research group recently reported that Cat's Claw's immune-stimulating alkaloids pteropodine and isopteropodine might have other properties and applications, reporting that these two chemicals have shown to have a positive modulating effect on brain neurotransmitters called 5-HT(2) receptors. These receptor sites are targets for drugs used in treating a variety of conditions, including depression, anxiety, eating disorders, chronic pain conditions, and obesity. 15 Anti-Oxidant Research in Argentina reports that Cat's Claw is an effective antioxidant. Other researchers in 2000 concluded that it is an antioxidant as well as a remarkably potent inhibitor of tumor necrosis factor (TNF) alpha production. TNF represents a model for tumor growth driven by an inflammatory cytokine chemical. Other researchers in the United States reported in 2002 that the anti-inflammatory actions of Cat's Claw are not attributable to immunostimulating alkaloids but rather to another group of chemicals called carboxyl alkyl esters. This would explain why a product comprised of mostly alkaloids showed only modest benefit to arthritis patients in a study by another group that was incidentally selling a special alkaloid preparation of Cat's Claw. The same group of anti-inflammatory glycoside chemicals also demonstrated in vitro antiviral properties in another earlier study. 197B 198B Klaus Keplinger, an Austrian scientist, started the analysis of Cat's Claw properties in 1974 and indicated Cat’s Claw properties/Action/Usage were effective for: cancer, HIV, AIDS, urinary track infection & inflammations, arthritis, rheumatism, sciatic nerve spasm, ulcers, tumors and as an immune booster. Studies indicate that cat's claw has the ability to protect cancer cells from maturing but to destroy cancer cells that are resistant to prescription medicines, the herb called graviola found in Get Well Soon is recommended. 19B Many of the studies published from the late 1970s to early 1990s indicated that the whole oxindole alkaloid fraction increased immune function by 50% when used in even relatively small amounts, having studied whole vine bark and/or root bark extracts, or six individually-tested oxindole alkaloids. These study results were substantiated by Canadian researchers at the University of Ottawa (1999) and by Peruvian researchers (1998, notably Peruvian Dr. Cabieses), both groups who worked with the whole vine extract. 20B Anti-Cancerous Cat’s Claw is also gaining popularity in the treatment of cancer. Taking with a high dose of Shark Cartilage, it has been reported that animal’s cancer can go into remission. At the very least, animals that are treated with Cat’s Claw for cancer end up living longer and side effect free, then those that are treated with the more conventional route. 201B 20B In addition to its immunostimulating activity, in vitro anticancerous properties have been documented for these alkaloids and other constituents in Cat's Claw. Five of the oxindole alkaloids have been clinically documented with in vitro antileukemic properties, and various root and bark extracts have demonstrated antitumorous and anticancerous properties. Italian researchers reported in a 2001 in vitro study that Cat's Claw directly inhibited the growth of a human breast cancer cell line by 90%, while another research group reported that it inhibited the binding of estrogens in human breast cancer cells in vitro. Swedish researchers documented it inhibited the growth of lymphoma and leukemia cells in vitro in 1998. Early reports on Keplinger's observatory trials with cancer patients taking Cat's Claw in conjunction with such traditional cancer therapies as chemotherapy and radiation reported fewer side effects to the traditional therapies, such as hair loss, weight loss, nausea, secondary infections, and skin problems. Subsequent researchers have reported that these effects might be possible in that Cat's Claw can aid in DNA cellular repair and prevent cells from mutating and it also can help prevent the loss of white blood cells and immune cell damage caused by many chemotherapy drugs (a common side effect called leukopenia). 203B Keplinger's work in 1974 and continuing through the 1980s led to several extracts of Cat's Claw being sold in Austria and Germany as herbal drugs, as well as the filing of four U.S. patents describing extraction procedures for the immune-stimulating oxindole alkaloids. These novel oxindole alkaloids produced worldwide interest in the medicinal properties of this valuable rainforest vine. Researchers in Spain, France, Japan, Germany, and Peru followed Keplinger, many of them confirming his previous research on the immunostimulating alkaloids in the vine and root. 204B 16 Allergies There have been a number of in vivo and in vitro studies conducted on the efficacy of Cat's Claw Extract. Most of the research has focused on its anti-inflammatory and immune stimulating properties. The University of Maryland Medical Center reports that cat's claw was used to treat rheumatoid arthritis, and may help animals with allergic reactions (hair loss, itching), geriatria (dull coat, lethargy), inflammation (muscle, prostate, stomach), hemorrhoids, mammary tumors, osteoarthritis, parvovirus, and arthritis. Flea Bites The Herbal Encyclopedia also lists cat's claw as part of a treatment for itching due to flea bites in cats. At the University Mayor de San Marcos, Lima, Peru, from 1990 to 1994, Dr. Ruiz used Una de Gato to treat cats and dogs with a wide range of difficult to treat problems. The animals receiving Una de Gato were healthier and lived about three years longer than untreated animals. During Dr. Ruiz' veterinary applications, Una de Gato helped animals with allergic reactions (hair loss, itching), geriatria (dull coat, lethargy), inflammation (muscle, prostate, stomach), hemorrhoids, mammary tumors, osteoarthritis, parvovirus, and arthritis.and arthritis. Natura Herbs plants are organically grown, wild harvested and processed in their organic state, without the use of pesticides, fumigation, genetically modified organisms, synthetic fertilizers, or ionizing radiation. Cat’s Claw is pure, unadulterated U. tomentosa and Natura Herbs does not include U. guianensis in the production or processing of any of our products. NON-GMO POLLEN: Pollen has been used for millennia for treating a host of health maladies, including use for wounds and diseases of the bowels, for wound dressing, as a general medical health and physical wellness support, to increase energy and vitality, to extend longevity, to aid recovery from long illness, to add weight during convalescence, to reduce cravings and addictions, to regulate the intestines, to build new blood and to prevent infectious disease including colds and flu. Bee pollen is considered one of nature's most perfect foods, containing carbohydrates, fat, approximately 40% protein, vitamins, minerals, twenty-two amino acids, an especially rich storehouse of B-vitamins, twenty-seven mineral salts, trace elements and several enzymes plus much more, used to build up the immune system to fight general illness and to counteract depression. It contains nearly all nutrients required by humans and animals. Bee pollen also has many healing properties. It can rejuvenate your pet’s body, stimulate organs and glands, enhance vitality, and has been associated with life extension. Working dogs and show dogs use pollen to enhance sports performance and to recover from extraneous physical exercise. Pollen contains natural hormonal substances that stimulate and nourish the reproductive system due to the presence of all essential amino acids, many vitamins and minerals and containing over 5,000 enzymes and coenzymes. Pollen is used holistically to increase sexual stamina and vitality and therapeutically to boost the body’s ability to heal, to provide the body with energy and to decrease LDL levels while increasing HDL levels. Pollen is also used traditionally and holistically to increase mental focus and alertness as well as provide energy and stamina during periods of heavy physical activity. Pollen has been named as a “cure all” by some and is touted for its anti-aging properties, for its antioxidant effects, and used for chronic prostatitis. Anti-Bacterial/Antibiotic Researchers have demonstrated that there is a substance in bee pollen that inhibits the development of numerous harmful bacteria. Experiments have shown bee pollen contains an antibiotic factor effective against salmonella and some strains of bacteria. On the clinical level, studies have shown that a regulatory effect on intestinal function can be attributed to bee pollen. The presence of a high proportion of cellulose and fiber in pollen, as well as the existence of antibiotic factors, all contribute to an explanation for this efficacious effect. Ingestion of bee pollen has a good effect on the composition of blood. A considerable and simultaneous increase of both 17 white and red blood cells is observed. When bee pollen is given to anemic patients, their levels of hemoglobin [oxygen-carrying red blood cells] increase considerably. Cholesterol It is reported that bee pollen in the diet acts to normalize cholesterol and triglyceride levels in the blood: Upon the regular ingestion of bee pollen, a reduction of cholesterol and riglycerides was observed. High-density lipoproteins (HDL) increased, while low-density lipoproteins (LDL) decreased. A normalization of blood serum cholesterol levels is also seen. 218B 219B Cancer In his summary, Dr. Robinson reveals the dramatic results: "In the untreated mice [the mice not given bee pollen], mammary tumors appeared as expected at an average of 31.3 weeks. Tumor incidence was 100 percent. In the postponement series, [the mice given bee pollen], the average [onset of tumors] was 41.1 weeks, a delay of 9.8 weeks being obtained. Seven mice in this series were still tumor-free at 56 to 62 weeks of age, when the tests were terminated. I would like to emphasize that these mice were especially bred to die from cancerous tumors. Without the protection of bee pollen in their food, the mice developed tumors and died right on schedule. 20B 21B One of the most important articles ever published on bee pollen comes from the United States Department of Agriculture. This article, entitled "Delay in the Appearance of Palpable Mammary Tumors in C3H Mice Following the Ingestion of PolIenized Food," is the work of William Robinson of the Bureau of Entomology, Agriculture Research Administration. It was published in the Journal of the National Cancer Institute way back in October 1948, five decades ago. According to the article, Dr. Robinson started with mice that had been specially bred to develop and subsequently die from tumors. He explains, "The age at which mice of this strain developed tumors ranged from 18 to 57 weeks, with an average appearance at 33 weeks. Tumor incidence was 100 percent." 2B Fertility Reporting to the French Academy of Medicine in 1956, Chauvin said, there were no side effects in the test animals who were administered pollen. Furthermore, the use of bee pollen gave the animals increased vitality and improved "powers of reproduction" because of boosted fertility. Recent studies conducted in 2009 confirm the anti-bacterial properties of pollen. Additionally, pollen has been confirmed as an excellent source of Bvitamins, protein, minerals, amino acids and enzymes. Recently, new laboratory techniques have been developed that make it easier to study the beneficial effects and the nutritional make-up of natural substances, including Pollen’s anti-oxidant benefits. 23B 24B The pollen used in this study was supplied by the Division of Bee Culture and, according to the report, "was the bee-gathered type." One group of mice was fed mice chow only; another group was fed mice chow with the addition of bee pollen at a ratio of 1 part bee pollen to 10,000 parts food. Dr. Robinson's article states, "Particular attention was given to the weight of the reated animals, since underweight can in itself bring about a delay in tumor development. No decrease in weight occurred in the animals receiving the pollenized food. Instead, a slight but fairly uniform increase was noted, possibly due to a nutritional factor in pollen." 25B Immune Boosting A report from the Agronomic Institute, Faculty of Zootechnics, Romania, showed the immune-strengthening effects of bee pollen. According to the report, "Comparative Studies Concerning Biochemical Characteristics of Beebread as Related to the Pollen Preserved in Honey" by Drs. E. Palos, Z. Voiculescu, and C. Andrei, "An increase has been recorded in the level of blood lymphocytes, gamma globulins, and proteins in those subjects given pollen in comparison with control groups. The most significant difference occurred in lymphocytes. These results thus signify a strengthening in the resistance of the organic system." Lymphocytes are the white blood cells that are the "soldiers" of the immune system. They are responsible for ridding the body of injurious 26B 27B 18 and harmful substances, including infected or diseased cells, mutant and cancerous cells, viruses, metabolic trash, and so on. Gamma globulin is a protein formed in the blood, and our ability to resist infection is closely related to this protein's activity. Allergies Bee pollen has the ability to consistently and noticeably minimize or potentially eliminate airborne allergies. Pollen is also used to alleviate allergies due to its capability to reduce the production of histamine that causes allergic reactions. Bee Pollen is also used to relieve anemia, constipation, nausea after radiation treatment, and may improve your sex life due to the presence of proteins, beneficial fats, the entire array of vitamins, as well as a great number of amino acids that can boost immunity and provide energy, stamina and strength. Bee pollen can help your pet through the process of allergy desensitization. Desensitization causes the body to produce antibodies that will cancel out the effects of the offending allergens when your pet is exposed to them. You start giving your pet a minute amount of bee pollen and work up to about ¼ teaspoon per 25 pounds. Care should be taken to observe any adverse reactions as some animals are allergic to pollen itself and/or bee venom/stings. Ideally, bee pollen should be taken at least six weeks before allergy season begin and then continued throughout the season for greatest effectiveness. Metabolism Because it is rich in nutrients and has the ability to speed up metabolism, pets that need to diet use it as a dietary supplement to replace caloric nutrients in weight loss programs. Pollen is also used to energize and restore a weakened nervous system, and helps nervous disorders and emotional conditions in both the young and old, including use as a treatment for Alzheimer’s disease. Horse owners often feed their horses bee pollen prior to races to take advantage of its abundant nutrition and it’s value as a high energy food source. Bee pollen is also being used on the farm by adding it to the diet of calves, piglets, chicks and adult laying hens. It is a complete and nutritious food source enhancing growth and total health as well as increasing fertility and egg production. One to two teaspoons of bee pollen is nutritionally equivalent to a hearty serving of vegetables. Feeding your dogs a nutritive-rich diet is of utmost importance to their health, happiness, reproduction (if they are a breeder) and optimum longevity. Complementing their diet with whole food supplements, such as bee pollen can help to prevent illness and increase wellness in your dogs. Obedience and coursing dogs do well with the addition of pllen to their diet. Cat owners, dog trainers, racehorse owners are reporting how well their animals are responding to taking bee pollen, reporting healthier appetites, added vitality and shinier coats. Many owners have also noted significant health improvements with arthritic conditions and incontinence in aging pets. Bee pollen was fed to hundreds of animals over a period of two years by scientist-researcher Dr. Remy Chauvin of the Institute for Bee \Culture in Bures-sur-Yvette, France. Reporting to the French Academy of Medicine in 1956, Chauvin said, there were no side effects in the test for animals. Furthermore, the use of bee pollen gave the animals increased vitality and improved "powers of reproduction" because of boosted fertility. Pollen is used for a number of health affects, including to rejuvenate the body and to keep the glands and organs healthy. It is also used to correct body chemistry and eliminate toxins as well as to strengthen the immune system. ORAC Tests The Oxygen Radical Absorbance Capacity (ORAC) test is an emerging standard by which science measures antioxidant activity in foods and natural supplements. Antioxidants are important to protect the body's cells from damage caused by free radicals (reactive oxygen species). Cell membranes are susceptible to free radicals because they are largely composed of fatty acids (lipid bi-layer). Poly-unsaturated fatty acids are particularly 19 susceptible to free-radical-mediated oxidation because of their unique structure. Cell membrane damage due to oxidation of fatty acid membrane components (lipid peroxidation) can lead to the disruption of the function and structure of whole cells. Furthermore, for normal health it is important to maintain normal levels of lipid peroxidation of lipoproteins. Dietary antioxidants, or free radical-scavengers, may play a preventive role in protecting a person's health. High levels of antioxidant activity, as determined by ORAC, have been found to be present in blueberries and black raspberries. When the ORAC scores of these berries became known, annual consumption of those fruits increased dramatically. Berries became famous as the foods possessing the most antioxidant activity of all the whole foods. The highest ORAC scores for wild blueberries is listed at 61 ORAC units (umole TE/g). Black raspberries scored higher at 164 ORAC units (see attached ORAC Comparison Chart). 239B Recently, CC Pollen tested Bee Pollen for ORAC antioxidant activity resulted in 247 ORAC units, the highest score ever recorded for any whole food. Thus, Bee Pollen has been shown to be at the top of the list of foods exhibiting antioxidant activity. 240B ANNATTO: Annatto is used by holistic vets to address a wide range of symptoms related to digestive, urinary and genital tract infections and dysfunction, including IBD, IBS, Leaky Gut Syndrome, for prostatits, for Inflammatory Bowel Disease as well as infections related to the uro-genital system, including Urinary Incontinence in dogs and cats. 241B 24B 243B Annatto has been used traditionally and holistically as an aphrodisiac and astringent, and to treat skin problems, fevers, dysentery, hepatitis; to treat skin problems, for liver disease, for good digestive system, to stimulate the bowels and to aid in elimination. 24B Annatto is used to treat prostate disorders and internal inflammation, arterial hypertension, high cholesterol, cystitis, obesity, renal insufficiency, and to eliminate uric acid. This decoction is also recommended as a vaginal antiseptic and wound healer, as a wash for skin infections, and for liver and stomach disorders. 245B Laboratory validation regarding Annatto’s traditional medicinal uses is largely confined to South America. A water extract of the root has demonstrated hypotensive activity in rats, confirming the traditional Peruvian herbal use. The same extract demonstrated smooth muscle-relaxant activity in guinea pigs and lowered gastric secretions in rats, which help to explain its use as a digestive aid and for stomach disorders. 246B Tinkle Tonic is recommended in the traditional treatment of pets for cystitis, obesity, renal insufficiency (kidney failure), to eliminate excess uric acid, for prostatitis, for acne vulgaris (seborrhea, scaly, red skin), for its actions against tumor cells, in the treatment of diabetes mellitus in dogs and cats 247B 248B Due to the presence of steroids in the leaves of the leaves, Annatto is used holistically as an anti-rheumatic treatment and for inflammations of the prostate and other UTI’s, or Urinary Tract Infections and Candida albicans, also due to the presence of flavonoides (compound phenolic acids that are classified as phytochemicals), 249B Annatto also demonstrates a wide ranging benefit to general health, functioning as an antioxidant, anticarcinogen, anti-inflammatory, as an immune system booster and astringent that tones, protects and supports the digestive, urinary and genital tracts. 250B Studies of Annatto have determined its use an effective diuretic, anti-gonorrheal and anti-bacterial as well as a valuable tool in the treatment of inflammation of the digestive, 251B 25B 20 urinary and genital tract problems, including prostate inflammation, where treatment usually requires antibacterial and diuretic products. Research indicates that Annatto is considered safe for long-term use. Anti-Gonorrheal Annatto demonstrated antigonorrheal activity in a 1995 study, and in other research, flower and leaf extracts demonstrated in vitro antibacterial activity against several bacteria, including E. coli and Staphylococcus, both which supported its use in traditional medicine systems for gonorrhea and other types of infections. Staph At the University of Waterloo (Canada), preliminary studies have shown the extract of Bixa Orellana has proven successful against gram-positive germs B. subtilis, Staph S. (aureua and S. faecalis); as well as E. coli, S. marescens, Cándida utilis and Aspergillus niger. The minimum inhibited concentration of the extract was of 4-16 mg/ml, while the germicidal activity was markedly higher at 16-64 mg/ml. The preliminary results of these studies have proven that Annatto is an effective diuretic, anti-gonorrheal and anti-bacterial and a valuable tool in the treatment of inflammation of the prostate and urinary and genital tract problems, where treatment usually requires antibacterial and diuretic products for treatment. Hypotensive A water extract of the root has demonstrated hypotensive activity in rats, confirming the traditional Peruvian herbal use. The same extract demonstrated smooth muscle-relaxant activity in guinea pigs and lowered gastric secretions in rats, which help to explain its use as a digestive aid and for stomach disorders. Annatto seed extracts have been documented to raise blood glucose levels in some species of animals and to lower it in others. Annatto leaves were reported in yet another study to possess aldose reductase inhibition actions, a process implicated in the advancement of diabetic neuropathy. Anti-Hermorrhagic A 2000 study confirmed the effectiveness of a leaf-and-bark extract at neutralizing hemorrhages in mice injected with snake venom, a practice used in Colombia for many years. Annatto demonstrated antigonorrheal activity in a 1995 study, and in other research, flower and leaf extracts demonstrated in vitro antibacterial activity against several bacteria, including E. coli and Staphylococcus. This supports its use in traditional medicine systems for gonorrhea and other types of infections. Candida/Anti-Bacterial/Anti-Microbial/Anti-Fungal Broad-spectrum in vitro antibacterial, antimicrobial and antifungal activity were found from an ethanolic extract of the dried seeds. An extract of the dried leaves showed greater potency, and both extracts were also active against Candida albicans. A water extract of the leaves showed platelet antiaggregant activity in vitro. In a 1989 study conducted by Jondiko and Patternden, a 1999 study by Mercadante A, and a 1990 Moulin Traffort study on Annatto’s growth inhibition on Candida, assessed and confirmed the effectiveness of Annatto against a variety of Candida strains as identified by the World Health Organization as important folk remedies used to treat persistent fungal infections. At the University of Waterloo (Canada), preliminary studies have shown the extract of Bixa Orellana has proven successful against significant bacterial and fungal infections, including gram-positive germs B. subtilis, Staph. aureua and Staph. Faecalis, as well as E. coli, S. marescens, Cándida utilis and Aspergillus niger. The minimum inhibited concentration of the extract was of 4-16 mg/ml, while the germicidal activity was markedly higher at 16-64 mg/ml. The use of Annatto in traditional medicine for Candida has also been extended to modern applications according to the 2003 Journal of Ethnopharmacology and a 2009 Journal of Applied Pharmaceutical Science 21 review for Annatto’s antimicrobial activity against bacterial pathogens including invasive or systemic Candidiasis due to corticosteroids, broad-spectrum antibiotics, burns, recent bacterial infection, recent surgery, granulocytopenia, bone marrow transplantation, solid organ transplantation (liver, kidney), parenteral hyper alimentation, hematologic malignancies, Foley catheters, solid neoplasms, recent chemotherapy or radiation therapy, prolonged hospitalization, severe trauma, gastrointestinal tract surgery, central intravascular access devices, premature birth, hemodialysis, acute and chronic renal failure and mechanical ventilation for longer than 3 days. Clinical studies conducted in Peru conclude that Bixa Orellana has been effective in treating Clotrimazol; as well as Gardenella vaginalis, Trichomoniasis, Candida albicans as well as all sexually transmitted diseases. Since studies are preliminary and ongoing, a final therapeutic regimen has not been established for Annatto; however, research indicates that no toxicity is associated with Annatto in cases of extended use. 273B Anti-Inflammatory The presence of steroids in the leaves of the Annatto suggest that plant steroids are responsible for the antiinflammatory properties that causes this popular medicine to be used as an anti-rheumatic treatment and for inflammations of the prostate. Also, due to the presence of flavonoides (compound phenolic acids that are classified as phytochemicals), Annatto demonstrates a wide-ranging benefit to general health, functioning as an antioxidant, anti-carcinogen, anti-inflammatory, as an immune system booster and diuretic and supports the urinary and genital tracts. 274B 275B A water extract of the leaves showed platelet antiaggregant activity in vitro according to Leung’s Pharmacology and Biological Activities. Administered to rats during and after whole body irradiation, bixin (200 μmol/kg p.o.) significantly reduced levels of lung collagen hydroxyproline and liver and serum lipid peroxidation values. At concentrations of 1–100 μM in vitro in rat spleen lymphocytes, bixin inhibited the activity of IgE, suggesting a possible antiallergic effect, and enhanced the production of IgM. 276B Laboratory validation regarding Annatto is extensive and traditional uses have been confirmed as well as new discoveries surrounding its plethora of plant protecting chemicals. A water extract of the root has demonstrated hypotensive activity in rats, as Peruvian herbal systems have practiced. The same extract demonstrated smooth muscle relaxant activity in guinea pigs and lowered gastric secretions in rats, which help to explain its use as a digestive aid and for stomach disorders for urinary tract infections, as well as its ability to tone and strengthen the bladder, connective skin and tissue. 27B 278B 279B 280B 281B 28B 283B Anti-Diabetic Annatto seed extracts have been documented to raise blood glucose levels in some species of animals and to lower it in others. Annatto leaves were reported in yet another study to possess aldose reductase inhibition actions, a process implicated in the advancement of diabetic neuropathy. A 2000 study confirmed the effectiveness of a leaf and bark extract at neutralizing hemorrhages in mice injected with snake venom, a practice used in Colombia for many years. 284B 285B 286B 287B 28B 289B IBD/Inflammatory Bowel Disease Research has confirmed Annatto’s use for Inflammatory Bowel Disease and its actions on reducing gastric secretions and relaxing the stomach and colon mechanisms. Upper GI lesions are usually evident by vomiting (stomach and upper small intestine) and lesions of the lower small intestinal tract and colon are likely to cause diarrhea and research has concluded that Annatto relaxes the stomach lining and intestines to reduce and prevent diarrhea in cases of intestinal distress. 290B 291B 22 Hypoglycemia The plant is used to lower blood sugar by stimulating peripheral usage of glucose. Hypoglycemia may cause seizures in dogs and in cases of low blood glucose, Annatto is cautioned to be used only as an adjunctive treatment and not as a replacement for glucose medications. Overall, Annatto is considered safe by holistic veterinarians for canine and feline diabetes mellitus treatment because it helps to increase plasma insulin levels. Annatto seed extracts have been documented to raise blood glucose levels in some species of animals and to lower it in others. Annatto leaves were reported in yet another study to possess aldose reductase inhibition actions, a process implicated in the advancement of diabetic neuropathy. A 2000 study confirmed the effectiveness of a leaf-and-bark extract at neutralizing hemorrhages in mice injected with snake venom, a practice used in Colombia for many years. Annatto demonstrated antigonorrheal activity in a 1995 study, and in other research, flower and leaf extracts demonstrated in vitro antibacterial activity against several bacteria, including E. coli and Staphylococcus. This supports its use in traditional medicine systems for gonorrhea and other types of infections. ZINC SULPHATE: Zinc is an essential mineral that is naturally present in some foods and is used for its wound healing remedies for dogs and cats. The effect of zinc treatment on the severity or duration of illness in dogs and cats is not well documented in Western medicine, but has been used traditionally for thousands of years. Researchers have hypothesized that zinc directly inhibits rhinovirus binding and replication in the nasal mucosa and suppresses inflammation [63, 64]. However, no data are available to support this hypothesis. Anti-Oxidant Zinc also has some antioxidant properties, which means that it can help protect cells in the body from the potential damage caused by free radicals. Zinc is especially important in the prostate and may protect it from early damage that could lead to cancer. As a component of many enzymes, zinc is involved in the metabolism of proteins, carbohydrates, lipids and energy. Researchers have suggested that both zinc and antioxidants delay the progression of age-related macular degeneration (AMD) and vision loss, possibly by preventing cellular damage in the retina. In a populationbased cohort study in the Netherlands, high dietary intake of zinc as well as beta carotene, vitamin C, and vitamin E was associated with reduced risk of AMD in elderly subjects. However, the authors of a systematic review and meta-analysis published in 2007 concluded that zinc is not effective for the primary prevention of early AMD, although zinc might reduce the risk of progression to advanced AMD. A Cochrane review concluded that the evidence supporting the use of antioxidant vitamins and zinc for AMD comes primarily from the AREDS study. Further research is required before public health recommendations can be made, but individuals who have or are developing AMD might wish to talk to their physician about using dietary supplements. Skin & Coat Zinc is an important mineral commonly found in dog and cat foods and supplements, products for skin and coat health and wound healing. Zinc is essential for protein synthesis and which helps to regulate the production of cells in the body's immune system and is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division. Zinc also supports normal growth and development during pregnancy, puppy and kitten stages, young adulthood and is required for proper sense of taste and smell. By boosting the immune system, zinc may also protect against fungal infections and various infectious disorders, such as conjunctivitis and pneumonia. 23 Digestive Zinc is found in virtually every cell in the body and is a component of over 200 enzymes. Enzymes are molecules involved in speeding up the chemical reactions necessary for body functions. Zinc functions in more enzymatic reactions than any other mineral; low zinc levels affect virtually every system of the body. Zinc is also required for proper action of many body hormones, including insulin, growth hormone, and sex hormones. Adequate zinc levels are absolutely essential to good health. Zinc is especially important to proper immune function, wound healing, sensory function, sexual function, and skin health. A deficiency in this mineral can lead to a condition called zinc-responsive dermatosis. 307B 308B Zinc plays an important role as a component of many enzymes and the catalysts of enzyme systems For many years, zinc has been used as an. Zinc is an important mineral which is essential for protein synthesis and which helps to regulate the production of cells in the body's immune system. By boosting the immune system, zinc may also protect against fungal infections and various infectious disorders, such as conjunctivitis and pneumonia. Zinc also has some antioxidant properties, which means that it helps protect cells in the body from the potential damage caused by free radicals. Zinc is especially important in the prostate and may protect it from early damage that could lead to cancer. As a component of many enzymes, zinc is involved in the metabolism of proteins, carbohydrates, lipids and energy. Zinc is important in the metabolism of vitamin A and collagen, cellular immunity, maintenance of taste acuity, and the development of reproductive organs. Zinc assists in maintaining the proper concentration of vitamin E in the blood. Zinc also plays a role in the regulation of appetite, stress level, taste, and smell. It is essential for normal growth and development, and for most aspects of reproduction in both males and females. Zinc also supports normal growth and development during pregnancy. 309B Dermal support Zinc-responsive dermatosis is an uncommon disease of dogs resulting from either an absolute or relative deficiency in zinc. Dermatological lesions are characterized by inflammation, hair loss, scales, and crusts that primarily affect the head. Two forms of the disease exist, including a familial form affecting Alaskan Malamutes and Siberian huskies and a form that affects growing puppies fed zinc-deficient or oversupplemented diets. 310B 31B Signs of Zinc-responsive Dermatosis nclude a dull coat with occasional areas of visible hair loss. The affected dogs may have difficulty absorbing zinc perhaps through a genetic mulfunction. Relative or absolute zinc deficiency is most likely to be seen in fast-growing giant breeds fed inadequate diets rich in soya and cereals. Puppies and kittens fed diet soy protein-based diet have poor coats characterized by thinning and slow hair growth and scaliness of the skin and ulcerations. 312B Metabolism Zinc is also important in the metabolism of vitamin A and collagen, cellular immunity, maintenance of taste acuity, and the development of reproductive organs. Zinc assists in maintaining the proper concentration of vitamin E in the blood. Zinc also plays a role in the regulation of appetite, stress level, taste, and smell. It is essential for normal growth and development, and for most aspects of reproduction in both males and females. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence. 31B 314B Eye Health/Macular Degeneration The Age-Related Eye Disease Study (AREDS), a large, randomized, placebo-controlled, clinical trial (n = 3,597), evaluated the effect of high doses of selected antioxidants (500 mg vitamin C, 400 IU vitamin E, and 15 mg beta-carotene) with or without zinc (80 mg as zinc oxide) on the development of advanced AMD in older individuals with varying degrees of AMD. Participants also received 2 mg copper to prevent the copper deficiency associated with high zinc intakes. After an average follow-up period of 6.3 years, supplementation with antioxidants plus zinc (but not antioxidants alone) significantly reduced the risk of developing advanced AMD and reduced visual acuity loss. Zinc supplementation alone significantly reduced the risk of developing 315B 24 advanced AMD in subjects at higher risk but not in the total study population. Visual acuity loss was not significantly affected by zinc supplementation alone. Two other small clinical trials evaluated the effects of supplementation with 200 mg zinc sulfate (providing 45 mg zinc) for 2 years in subjects with drusen or macular degeneration. Zinc supplementation significantly reduced visual acuity loss in one of the studies but had no effect in the other. Cold Preventative In a randomized, double-blind, placebo-controlled clinical trial, 50 subjects (within 24 hours of developing the common cold) took a zinc acetate lozenge (13.3 mg zinc) or placebo every 2–3 wakeful hours. Compared with placebo, the zinc lozenges significantly reduced the duration of cold symptoms (cough, nasal discharge, and muscle aches). In another clinical trial involving 273 participants with experimentally induced colds, zinc gluconate lozenges (providing 13.3 mg zinc) significantly reduced the duration of illness compared with placebo but had no effect on symptom severity [66]. However, treatment with zinc acetate lozenges (providing 5 or 11.5 mg zinc) had no effect on either cold duration or severity. Neither zinc gluconate nor zinc acetate lozenges affected the duration or severity of cold symptoms in 281 subjects with natural (not experimentally induced) colds in another trial. In 77 participants with natural colds, a combination of zinc gluconate nasal spray and zinc orotate lozenges (37 mg zinc every 2–3 wakeful hours) was also found to have no effect on the number of asymptomatic patients after 7 days of treatment. In September of 2007, Caruso and colleagues published a structured review of the effects of zinc lozenges, nasal sprays, and nasal gels on the common cold. Of the 14 randomized, placebo-controlled studies included, 7 (5 using zinc lozenges, 2 using a nasal gel) showed that the zinc treatment had a beneficial effect and 7 (5 using zinc lozenges, 1 using a nasal spray, and 1 using lozenges and a nasal spray) showed no effect. A Cochrane review of the effects of zinc lozenges on cold symptoms also reported inconclusive findings [68], although the author of another review concluded that zinc can reduce the duration and severity of cold symptoms. Anemia Iron-deficiency anemia is a serious world-wide public health problem. Iron fortification programs have been credited with improving the iron status of millions of women, infants, and children. Fortification of foods with iron does not significantly affect zinc absorption. However, large amounts of supplemental iron (greater than 25 mg) might decrease zinc absorption. Taking iron supplements between meals helps decrease its effect on zinc absorption. High zinc intakes can inhibit copper absorption, sometimes producing copper deficiency and associated anemia. For this reason, dietary supplement formulations containing high levels of zinc, such as the one used in the AREDS study, sometimes contain copper. Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence and is required for proper sense of taste and smell. A daily intake of zinc is required to maintain a steady state because the body has no specialized zinc storage system. TINKLE TONIC: COOL, NATURAL, PLANT CHEMICALS Cat’s Claw Extract: Cat's Claw has several groups of plant chemicals that account for much of the plant's actions and uses. The best understood is a group of oxidole alkaloids that have been documented with immune25 stimulant and antileukemic properties. Another group of chemicals are called quinovic acid glycosides which have documented anti-inflammatory and antiviral actions. Antioxidant chemicals (tannins, catechins and procyanidins) as well as plant sterols (beta-sitosterol, stigmasterol, and campesterol) account for the plant's antiinflammatory properties. A class of compounds known as carboxyl alkyl esters found in Cat's Claw has been documented with immunostimulant, anti-inflammatory, anticancerous, and cell-repairing properties. Cat's Claw also contains ajmalicine, akuammigine, campesterol, catechin, carboxyl alkyl esters, chlorogenic acid, cinchonain, corynantheine, corynoxeine, daucosterol, epicatechin, harman, hirsuteine, hirsutine, isopteropodine, loganic acid, lyaloside, mitraphylline, oleanolic acid, palmitoleic acid, procyanidins, pteropodine quinovic acid glycosides, rhynchophylline, rutin, sitosterols, speciophylline, stigmasterol, strictosidines, uncarine A thru F, and vaccenic acid. 328B Pollen: Pollen plant chemicals include protein, carbohydrates, vitamin A, vitamin B1, B2, B6, B12, niacin, vitamin C, vitamin D, vitamin E and K, choline, inositol, rutin & other bioflavonoids, nicotinic acid, pantothenic acid, folic acid, ascorbic acid, lecithin, cysteine, calcium, magnesium, iron, copper, phosphorous, sodium, potassium, silicon, sulpher, zinc and selenium, polysaccharides, protein, minerals, carbohydrates, lipids and essential fatty acids (alpha-linolenic and linolenic), enzymes, coenzymes, and other nutritional factors. The composition of Pollen is up to 35% complete protein (primarily albumin & nitrógen proteíns), a rich storehouse of B-vitamins, 27 mineral salts, trace elements and several enzymes. Pollen includes both macro and micronutrients including carotenoids and 22 amino acids such as tryptophan, lysine and cystine. 329B Annatto: Analysis of annatto seeds indicates that they contain 40% to 45% cellulose, 3.5% to 5.5% sucrose, 0.3% to 0.9% essential oil, 3% fixed oil, 4.5% to 5.5% pigments, and 13% to 16% protein, as well as alpha- and beta-carotenoids and other constituents. Annatto oil is extracted from the seeds and is the main source of pigments named bixin and norbixin, which are classified as carotenoids. Bixin, extracted and used as a food colorant, has been shown to protect against ultraviolet rays and to have antioxidant and liver protective properties in clinical research. In addition to bixin and norbixin, annatto contains bixaghanene, bixein, bixol, crocetin, ellagic acid, ishwarane, isobixin, phenylalanine, salicylic acid, threonine, tomentosic acid, and tryptophan. 30B 31B Zinc Sulphate: Zinc contains phytates including zinc gluconate, zinc sulfate, and zinc acetate. The main biochemicals in which zinc has been found to be necessary include: enzymes and enzymatic function, carbohydrate metabolism and protein synthesis. The percentage of elemental zinc varies by form. For example, approximately 23% of zinc sulfate consists of elemental zinc; thus, 220 mg of zinc sulfate contains 50 mg of elemental zinc. 32B In addition to bixin and norbixin, annatto contains bixaghanene, bixein, bixol, crocetin, ellagic acid, ishwarane, isobixin, phenylalanine, salicylic acid, threonine, tomentosic acid, and tryptophan. Phytochemicals include delta-tocotrienol (apparently, Bixa orellana L. has the highest content among all the plants (Frega, Mozzon & Bocci, 1998), apocarotenoids, methyl (9Z)-8’-oxo-6, 8’diapocarten-6-oate (Haberli & Pfander 1999), methyl Z)-10’-oxo-6, 10’diapocaroten-6-oate (Haberli & Pfander 1999), methyl (9Z)-14’-oxo-6,14’-diapocaroten-6oate (Haberli & Pfander 1999), minor carotenoids, beta-carotene, cryptoxantin, lutein, zeaxanthin, orellin (yellow color), ellagic acid, salicylic acid, tomentosic acid, bixaghanene, bixein, bixin (9'Z-6,6'-diapocaroten6,6'-dioate), bixol, crocetin, phenylalanine, geranilgeraniol (Mercadante, Steck & Pfander 1999), ishwarane (tricyclic sesquiterpenic hydrocarbon), isobixin, norbixin, threonine, tryptophan. 3B The chemical composition of the seeds is as follows cellulose 40-45%, sucrose 3.5-5.5%, essential oil 0.3-0.9%, fixed oil 3%, pigments 4.5-5.5%, protein 13-16%, alfa carotenoids, beta carotenoids, tannins, ethereal oils, saponins, mustard oil-like substances, monoterpenes, sesquiterpenes and mucilages. Annatto also contains lipids (17, 5%), linoleic acid, alpha-linolenic acid and oleic acid. 34B 26 TINKLE TONIC: FASCIANTING RESEARCH 1. The Natural Health Bible for Dogs and Cats, Shawn Messonier, DVM 2. The Nature of Animal Healing, Goldstein, Marty D.V.M. 3. Veterinarians Guide to Natural Remedies for Cats, Martin Zucker 1999 4. The Complete Handbook for the Dog and Cat, Juliette de Bairacli Levy 5. The Herbal Encyclopedia 6. Whole Dog Journal 7. Dr. Gary, Clinician’s Handbook of Natural Healing 8. Dr. James Duke, The Green Pharmacy 9. Ehow 10. Natural News 11. Natural Ark 12. R. Kidd, Dr. Kidd's Guide to Herbal Dog Care (Storey Publishing, 2000). M.L. Wulff-Tilford and G.L. Tilford, Herbs for Pets (Bowtie Press, 1999). 13. Hompeopathic Care for Cats & Dogs. Don Hamilton, DVM. 2010 14. Newall, C. A., Anderson, L. A. and Phillipson, J. D.: 1996. The British Herbal Pharmacopoeia 1983, British Herbal Pharmacopoeia 1990, British Pharmaceutical Codex 1963, Martindale 30th edition. The British Herbal Pharmacopoeia: 1983 as a sedative, mild anodyne, hypnotic, spasmolytic, carminative, hypotensive. Indicated for hysterical states, excitability, insomnia, hypochondriasis, migraine, cramp and rheumatic pain. Another source [Weiss, R.F.: 1986] says that the three main areas of use for valerian are for nervous excitement, nervous sleeplessness, and nervous palpitations. 15. WebMD 16. Herbs2000 17. Pet Nutrition 18. The Daily Puppy 19. Herbal Legacy 20. Bright Hub 21. PubMed 22. Berges RR, Windeler J, Trampisch HJ, et al. “Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia”. Lancet 1995;345:1529–32. 27 Cat’s Claw Extract: 360B Immunostimulant & Immunomodulatory Actions: 1. Spelman, K., et al. "Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators." Altern. Med. Rev. 2006 Jun; 11(2): 128-50. 361B 362B 2. Eberlin, S., et al. “Uncaria tomentosa extract increases the number of myeloid progenitor cells in the bone marrow of mice infected with Listeria monocytogenes.” Int. Immunopharmacol. 2005; 5(78):1235-46. 36B 3. Deharo, E., et al. ”In vitro immunomodulatory activity of plants used by the Tacana ethnic group in Bolivia.” Phytomedicine. 2004 Sep; 11(6): 516-22. 364B 4. Lamm, S., et al, “Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100." Phytomedicine. 2001; 8(4): 267–74. 365B 5. Sheng Y, et al., “Treatment of chemotherapy-induced leucopenia in a rat model with aqueous extract from Uncaria tomentosa.” Phytomedicine. 2000; 7(2): 137–43. 36B 6. Lemaire, I., et al. “Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (una de gato).” J. Ethnopharmacol. 1999; 64(2): 109–15. 367B 7. Marina, M. D. “Evaluacion de la actividal immunoestimulante de Uncaria tomentosa (Willd.) DC. Una de gato en ratones albinos." Biodiversidad Salud. 1998; 1(1): 16–19. 368B 8. Keplinger, H., et al. “Oxindole alkaloids having properties stimulating the immunologic system and preparation containing same.” United States patent 5,302,611; April 12, 1994 369B 9. Wagner, H., et al. “Die Alkaloide von Uncaria tomentosa und ihre Phagozytose-steigernde Wirkung." Planta Med. 1985; 51: 419–23. 370B 10. Hemingway, S. R. and J. D. Phillipson. “Alkaloids from South American species of Uncaria (Rubiaceae)." J. Pharm. Pharmacol. 1974 suppl.; 26: 113p. 371B Anti-inflammatory Actions: 1. Hardin, S. R. "Cat's claw: An Amazonian vine decreases inflammation in osteoarthritis." Complement. Ther. Clin. Pract. 2007 Feb; 13(1): 25-8. 372B 37B 2. Allen-Hall, L., et al. "Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates the expression if IL-1beta and TNF-alpha." J. Ethnopharmacol. 2007 Jan; 109(2): 312-7. 374B 3. Miller, M. J., et al. "The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta." BMC Complement. Altern. Med. 2006 Apr; 6: 13. 375B 4. Miller, M. J., et al. "Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711]." J. Inflamm. 2005 Oct; 2:11. 376B 5. Valerio, L. G., et al. "Toxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii): a critical synopsis." Toxicol. Rev. 2005; 24(1): 11-35. 37B 28 6. Setty, A. R., et al. "Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects." Semin. Arthritis Rheum. 2005; 34(6): 773-84. 7. Sheng, Y., et al. “An active ingredient of Cat's Claw water extracts: identification and efficacy of quinic acid.” J. Ethnopharmacol. 2005 Jan 15; 96(3): 8. Aguilar, J. L., et al. “Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae).” J. Ethnopharmacol. 2002; 81(2): 271–76. 9. Sandoval, M., et al., “Anti-inflammatory and antioxidant activities of cat’s claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content." Phytomedicine. 2002; 9(4): 325–37. 1. Mur, E., et al. “Randomized double blind trial of an extract from the pentacyclic alkaloid-10. chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis.” J. Rheumatol. 2002 Apr; 29(4): 678–81. 10. Sandoval-Chacon, M., et al. “Anti-inflammatory actions of cat’s claw: the role of NF-kappaB.” Aliment. Pharmacol. Ther. 1998; 12(12): 1279–89. 11. Recio, M. C., et al. “Structural requirements for the anti-inflammatory activity of natural triterpenoids.” Planta Med. 1995; 61(2): 182–85. 12. Aquino, R., et al. “Plant metabolites. New compounds and anti-inflammatory activity of Uncaria tomentosa." J. Nat. Prod. 1991; 54: 453–59. 13. Cerri, R., et al. “New quinovic acid glycosides from Uncaria tomentosa." J. Nat. Prod. 1988; 51: 257– 61. Anticancerous & Antitumor Actions: 1. Gonzales, G.F., et al. "Medicinal plants from Peru: a review of plants as potential agents against cancer." Anticancer Agents Med. Chem. 2006 Sep; 6(5): 429-44. 2. De Martino, L., et al. "Proapoptotic effect of Uncaria tomentosa extracts." J. Ethnopharmacol. 2006 Aug; 107(1): 91-4. 3. Bacher, N., et al. "Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1arrested and bcl-2-expressing acute lymphoblastic leukaemia cells." Br. J. Haematol. 2006 Mar; 132(5): 615-22. 4. Riva, L., et al. “The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line." Anticancer Res. 2001; 21(4A): 2457–61. 5. Muhammad, I., et al. “Investigation of Una de Gato I. 7-Deoxyloganic acid and 15N NMR spectroscopic studies on pentacyclic oxindole alkaloids from Uncaria tomentosa." Phytochemistry. 2001; 57(5): 781– 5. 6. Sheng, Y., et al. “Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa." Anticancer Res. 1998; 18(5A): 3363–68. 7. Salazar, E. L., et al. “Depletion of specific binding sites for estrogen receptor by Uncaria tomentosa." Proc. West. Pharmacol. Soc. 1998; 41(1): 123–124. 8. Stuppner, H., et al. “A differential sensitivity of oxindole alkaloids to normal and leukemic cell lines.” Planta Med. (1993 suppl.); 59: A583. 29 9. Rizzi, R., et al. “Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts." J. Ethnopharmacol. 1993; 38: 63–77. 8B 10. Peluso, G., et al. “Effetto antiproliferativo su cellule tumorali di estrattie metaboliti da Uncaria tomentosa. Studi in vitro sulla loro azione DNA polimerasi.” 11 Congreso Italo-Peruano de Etnomedicina Andina, Lima, Peru, October 27–30, 1993, 21–2. 9B 11. Rizzi, R., et al. “Bacterial cytotoxicity, mutagenicity and antimutagenicity of Uncaria tomentosa and its extracts. Antimutagenic activity of Uncaria tomentosa in humans." Premiere Colloque Européan d'Ethnopharmacologie, Metz, France, March 22–24, 1990. 10B Cellular Protective & Antioxidant Actions: 1. Mammone, T., et al. "A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin." Phytother. Res. 2006; 20(3): 178-83. 38B 389B 2. Kuras, M., et al. "Changes in chromosome structure, mitotic activity and nuclear DNA content from cells of Allium Test induced by bark water extract of Uncaria tomentosa (Willd.) DC." J. Ethnopharmacol. 2006 Sep; 107(2): 211-21. 390B 3. Pilarski, R., et al. "Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC." J. Ethnopharmacol. 2006 Mar; 104(1-2): 18-23. 391B 4. Cisneros, F. J., et al. “An Uncaria tomentosa (cat's claw) extract protects mice against ozone-induced lung inflammation.” J. Ethnopharmacol. 2005 Jan; 96(3): 355-64. 392B 5. Goncalves, C., et al. “Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity.” Phytochemistry. 2005; 66(1): 89-98. 39B 6. Romero-Jimenez, M., et al. “Genotoxicity and anti-genotoxicity of some traditional medicinal herbs.” Mutat. Res. 2005 Aug; 585(1-2): 147-55. 394B 7. Pilarski, R., et al. “Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC.” J. Ethnopharmacol. 2005 Sep 29; 395B 8. Sheng, Y., et al. “DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study." Phytomedicine. 2001; 8(4): 275–82. 396B 9. Sheng, Y., et al. “Enhanced DNA repair, immune function and reduced toxicity of C-Med-100, a novel aqueous extract from Uncaria tomentosa." J. Ethnopharmacol. 2000; 69(2): 115–26. 397B 10. Sandoval, M., et al. “Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection.” Free Radic. Biol. Med. 2000; 29(1): 71–8. 398B 11. Desmarchelier, C., et al. “Evaluation of the in vitro antioxidant activity in extracts of Uncaria tomentosa (Willd.) DC." Phytother. Res. 1997; 11(3): 254–256. 39B 12. Chan-Xun, C., et al. “Inhibitory effect of rhynchophylline on platelet aggregation and thrombosis.” Acta Pharmacologica Sinica 1992; 13(2): 126–30. 40B Actions on the Brain and Memory: 1. Jurgensen, S., et al. “Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa.” Pharmacol. Biochem. Behav. 2005 Jul; 81(3): 466-77. 401B 402B 30 1. 2.Kang, T. H., et al. “Pteropodine and isopteropodine positively modulate the function of rat muscarinic M(1) and 5-HT(2) receptors expressed in Xenopus oocyte.” Eur. J. Pharmacol. 2002 May; 444(1-2): 3945. 2. Mohamed, A. F., et al. “ Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.” J. Pharm. Pharmacol. 2001; 52(12): 1553–61. 3. Roth, B. L., et al. “Insights into the structure and function of 5-HT(2) family serotonin receptors reveal novel strategies for therapeutic target development.” Expert Opin. Ther. Targets 2001 Dec; 5(6): 685695. 4. Castillo, G. "Methods of isolation of amyloid inhibitory ingredients within Uncaria tomentosa." US Patent No 7,029,710, April, 18, 2006. 5. Castillo, G. " Methods of isolating amyloid-inhibiting compounds and use of compounds isolated from Uncaria tomentosa and related plants." US Patent No. 6,929,808, August 16, 2005. 6. Castillo, G., et al. “Pharmaceutical compositions containing Uncaria tomentosa extract for treating Alzheimer's disease and other amyloidoses." Patent-Pct. Int. Paol. 1998; 00 33,659: 67pp. Antimicrobial Actions: 1. Kloucek, P., et al. “Antibacterial screening of some Peruvian medicinal plants used in Calleria District.” J. Ethnopharmacol. 2005 Jun; 99(2): 309-12. 2. Garcia, R., et al. “Antimicrobial activity of isopteropodine.” Z. Naturforsch. 2005; 60(5-6): 385-8. 3. Aquino, R., et al. “Plant metabolites. Structure and in vitro antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda." J. Nat. Prod. 1989; 4(52): 679–85. 4. The Mayo Clinic is presently studying Cat’s Claw to determine if it will help reduce hypertension. 5. The Mayo Clinic a Guide for Alternative Medicine. The Time Inc Editor Brent Baur , M.D MEMORIAL SLOAN KETTERING RESEARCH Scientific Name Uncaria tomentosa Common Name Una de gato, life-giving vine of Peru, hawk's claw Clinical Summary Cat's claw is a vine native to South America. The bark of this plant has been used in traditional medicine to treat diseases. It is also a very popular immune-enhancing supplement. In vitro studies show that the alkaloids from Cat's claw enhance phagocytosis, display immunomodulatory properties, alleviate inflammation, and possess anti-viral activity. Cat's claw is also thought to have anticancer activities and lab results demonstrated growth inhibitory effects on glioma and neuroblastoma cells as well as promyelocytic leukemia cells. However, no human studies have been conducted to evaluate efficacy. Reported adverse reactions include hypotension and diarrhea. An additive effect with anticoagulants or hypotensives is possible; therefore caution should be exercised. 31 Purported uses Cancer treatment GI disorders HIV and AIDS Inflammation 42B 423B 42B 425B 426B Constituents Oxindole alkaloids: Isopteropodine, pteropodine, rhynchophylline, mytraphylline, speciphylline Indole alkaloidal glucosides: Cadambine, 3-dihydrocadambine, and 3-isodihydrocadambine Hirsutine Quinovic acid glycosides Tannins Polyphenols Catechins Beta sitosterol 427B 428B 429B 430B 431B 432B 43B 43B 435B Mechanism of Action The oxindole alkaloids are claimed to have immunostimulating properties in vitro, increasing phagocytotic activity and synthesis of WBCs and enhancing T-helper cell function. The major alkaloid, rhynchophylline, is claimed to be anti-hypertensive; it relaxes the endothelial cells of blood vessels, dilates peripheral blood vessels, inhibits sympathetic nervous system activities, and lowers the heart rate and blood cholesterol. The alkaloid mytraphylline has diuretic properties, and hirsutine inhibits urinary bladder contractions and possesses local anesthetic. The anti-inflammatory activity may be caused by the inhibition of TNF-alpha production. Uncaria tomentosa water extracts have been shown to enhance DNA repair after chemical-induced damage. 436B 437B Literature Summary and Critique Animal and in vitro data exist in cancer, immunostimulant, inflammation, and antiviral studies. Human studies are lacking, and further research is needed. 438B 439B References 1. Riva L, et al. The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line. Anticancer Res 2001;21:2457-61. 40B 41B 2. Sandoval M, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-8. 42B 3. Sandoval M, et al. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine 2002;9:325-37. 43B 4. Sheng Y, Bryngelsson C, Pero R. Enhanced DNA repair, immune function and reduced toxicity of CMED-100, a novel aqueous extract from Uncaria tomentosa. J Ethnopharmacol 2000;69:115-26. 4B 5. Reis SR, Valente LM, Sampaio AL, et al. Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2. Int Immunopharmacol. Mar 2008;8(3):468-476. 45B 6. Garcia Prado E, Garcia Gimenez MD, De la Puerta Vazquez R, Espartero Sanchez JL, Saenz Rodriguez MT. Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines. Phytomedicine. Apr 2007;14(4):280-284. 46B 32 7. Pilarski R, Poczekaj-Kostrzewska M, Ciesiolka D, Szyfter K, Gulewicz K. Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells. Pharmacol Rep. SepOct 2007;59(5):565-572. 8. Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health-Syst Pharm 2002;59:339-47. 9. Hemingway SR, Phillipson JD. Proceedings: alkaloids from south American species of Uncaria (Rubiaceae). J Pharm Pharmacol 1974;26(suppl):113. 10. Wirth C, et al. Pharmacologically active procyanidines from the bark of Uncaria tomentose. Phytomedicine 1997;4:265-6. 11. Aquino R, et al. Plant metabolites: New compounds and anti-inflammatory activity of Uncaria tomentosa. J Nat Prod 1991;54:453-9. 12. Rizzi R, et al. Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. J Ethnopharmacol 1993;38:63-77. 13. Sheng Y, et al. DNA repair of aqueous extracts of Uncaria tomentosa in a human volunteer study. Phytomedicine 2001;8:275-82. 14. Hilepo JN, et al. Acute renal failure caused by 'cat's claw' herbal remedy in a patient with systemic lupus erythematosus. Nephron 1997;77:361. OTHER RESEARCH: Cat's claw. Natural Medicines Comprehensive Database Web site. Accessed on July 5, 2007. Cat's claw (Uncaria tomentosa, Uncaria guianensis). Natural Standard Database Web site. Accessed on July 3, 2007. “Uncaria tomentosa, also known as cat’s claw, an herb from the highlands of the Peruvian Amazon, has been used by natives for hundreds of years to treat immunologic and digestive disorders. Research began in the 1970s to discover the benefits of this plant in relieving symptoms of cancers, arthritis, and other ailments. It has the ability to cleanse the digestive tract, aiding victims of Crohn’s, colitis, gastritis and more. In a 1989 study by Klaus Keplinger, several alkaloid oxidants found in the plant’s roots showed an ability to stimulate the immune system. The principal alkaloids are isopteropodine and rynchophyiline. Extracts of cat’s claw mixed with AZT in an experimental drug, called Krallendom, were effective in reducing symptoms in AIDS patients in Austria. The plant has been useful in reducing secondary effects of radiation and chemotherapy in cancer victims as well.” Steinberg PN Sidahora. 1995 Apr-May;:35-6. 1. An extract of Uncaria tomentosa inhibiting cell division and NF-kappa B activity without inducing cell death. Akesson C, Lindgren H, Pero RW, Leanderson T, Ivars F. Section for Immunology, Department of Cell and Molecular Biology, BMC I:13, Lund University, Lund, SE-221 84, Sweden. Int Immunopharmacol. 2003 Dec;3(13-14):1889-900. PMID: 14636838 [PubMed - in process] 2. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Sheng Y, Pero RW, Amiri A, Bryngelsson C. 33 Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Anticancer Res. 1998 Sep-Oct;18(5A):3363-8 PMID: 9858909 [PubMed - indexed for MEDLINE] 467B 468B 469B 3. Antiinflammatory actions of cat’s claw: the role of NF-kappaB. Sandoval-Chacon M, Thompson JH, Zhang XJ, Liu X, Mannick EE, Sadowska-Krowicka H, Charbonnet RM, Clark DA, Miller MJ. LSU Medical Center, Department of Paediatrics and Stanley S. Scott Cancer Center, New Orleans, LA 70112, USA. Aliment Pharmacol Ther. 1998 Dec;12(12):1279-89. PMID: 9882039 [PubMed - indexed for MEDLINE] 470B 471B 472B 473B 47B 4. Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ. Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. [email protected] Free Radic Biol Med. 2000 Jul 1;29(1):71-8 PMID: 10962207 [PubMed - indexed for MEDLINE] 475B 476B 47B 478B 479B 5. Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis. Miller MJ, Angeles FM, Reuter BK, Bobrowski P, Sandoval M. Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. [email protected] BMC Complement Altern Med. 2001;1(1):11. Epub 2001 Dec 10 PMID: 11749672 [PubMed - indexed for MEDLINE] 480B 481B 482B 483B 48B 6. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Sheng Y, Li L, Holmgren K, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2001 Jul;8(4):275-82 PMID: 11515717 [PubMed - indexed for MEDLINE] 485B 486B 487B 48B 489B 7. Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test. Mohamed AF, Matsumoto K, Tabata K, Takayama H, Kitajima M, Watanabe H. Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan. PMID: 11197086 [PubMed - indexed for MEDLINE] 490B 491B 492B 493B 8. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa. Sheng Y, Bryngelsson C, Pero RW. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] J Ethnopharmacol. 2000 Feb;69(2):115-26. PMID: 10687868 [PubMed - indexed for MEDLINE] 49B 495B 496B 497B 498B 9. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa. Sheng Y, Pero RW, Wagner H. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2000 Apr;7(2):137-43. 49B 50B 501B 502B 34 PMID: 10839217 [PubMed - indexed for MEDLINE] 10. Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100. Lamm S, Sheng Y, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. Phytomedicine. 2001 Jul;8(4):267-74 PMID: 11515716 [PubMed - indexed for MEDLINE] 11. In vitro Effects of Two Extracts and Two Pure Alkaloid Preparations of Uncaria tomentosa on Peripheral Blood Mononuclear Cells. Winkler C, Wirleitner B, Schroecksnadel K, Schennach H, Mur E, Fuchs D. Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria. Planta Med. 2004 Mar;70(3):205-10. PMID: 15114496 [PubMed - in process] 12. An extract of Uncaria tomentosa inhibiting cell division and NF-kappa B activity without inducing cell death. Akesson C, Lindgren H, Pero RW, Leanderson T, Ivars F. Section for Immunology, Department of Cell and Molecular Biology, BMC I:13, Lund University, Lund, SE-221 84, Sweden. Int Immunopharmacol. 2003 Dec;3(13-14):1889-900. Previous reports have demonstrated that extracts of the plant Uncaria tomentosa inhibit tumor cell proliferation and inflammatory responses. We have confirmed that C-Med 100, a hot water extract of this plant, inhibits tumor cell proliferation albeit with variable efficiency. We extend these findings by showing that this extract also inhibits proliferation of normal mouse T and B lymphocytes and that the inhibition is not caused by toxicity or by induction of apoptosis. Further, the extract did not interfere with IL-2 production nor IL-2 receptor signaling. Since there was no discrete cell cycle block in C-Med 100-treated cells, we propose that retarded cell cycle progression caused the inhibition of proliferation. Collectively, these data suggested interference with a common pathway controlling cell growth and cell cycle progression. Indeed, we provide direct evidence that C-Med 100 inhibits nuclear factor kappa B (NF-kappa B) activity and propose that this at least partially causes the inhibition of proliferation. PMID: 14636838 [PubMed - in process] 13. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Sheng Y, Pero RW, Amiri A, Bryngelsson C. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Anticancer Res. 1998 Sep-Oct;18(5A):3363-8 Growth inhibitory activities of novel water extracts of Uncaria tomentosa (C-Med-100) were examined in vitro using two human leukemic cell lines (K562 and HL60) and one human EBV-transformed B lymphoma cell line (Raji). The proliferative capacities of HL60 and Raji cells were strongly suppressed in the presence of the C-Med-100 while K562 was more resistant to the inhibition. Furthermore, the antiproliferative effect was confirmed using the clonogenic assay, which showed a very close correlation between C-Med-100 concentration and the surviving fraction. The suppressive effect of Uncaria tomentosa extracts on tumor cell growth appears to be mediated through induction of apoptosis which was demonstrated by characteristic morphological changes, internucleosomal DNA fragmentation after agarose gel electrophoresis and DNA fragmentation quantification. C-Med-100 induced a delayed type of apoptosis becoming most dose-dependently prominent after 48 hours of exposure. Both DNA single and double strand breaks were increased 24 hours after C-Med-100 treatment, which suggested a well- 35 established linkage between the DNA damage and apoptosis. The induction of DNA strand breaks coupled to apoptosis may explain the growth inhibition of the tumor cells by Uncaria tomentosa extracts. These results provide the first direct evidence for the antitumor properties of Uncaria tomentosa extracts to be via a mechanism of selective induction of apoptosis. PMID: 9858909 [PubMed - indexed for MEDLINE] 52B 14. Antiinflammatory actions of cat’s claw: the role of NF-kappaB. Sandoval-Chacon M, Thompson JH, Zhang XJ, Liu X, Mannick EE, Sadowska-Krowicka H, Charbonnet RM, Clark DA, Miller MJ. LSU Medical Center, Department of Paediatrics and Stanley S. Scott Cancer Center, New Orleans, LA 70112, USA. Aliment Pharmacol Ther. 1998 Dec;12(12):1279-89. BACKGROUND: Uncaria tomentosa is a vine commonly known as cat’s claw or ‘una de gato’ (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. PURPOSE: The aim of this study was to determine the proposed anti-inflammatory properties of cat’s claw. Specifically: (i) does a bark extract of cat’s claw protect against oxidant-induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. METHODS: Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 microM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF-kappaB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). RESULTS: The administration of UG (100 microg/mL) attenuated (P < 0.05) peroxynitrite-induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat’s claw inhibited lipopolysaccharide-induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF-kappaB. Cat’s claw markedly attenuated indomethacin-enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. CONCLUSIONS: Cat’s claw protects cells against oxidative stress and negated the activation of NFkappaB. These studies provide a mechanistic evidence for the widely held belief that cat’s claw is an effective anti-inflammatory agent. PMID: 9882039 [PubMed - indexed for MEDLINE] 526B 527B 528B 529B 530B 531B 15. Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ. Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. [email protected] Free Radic Biol Med. 2000 Jul 1;29(1):71-8 Cat’s claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat’s claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat’s claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 microg/ml, p <.05). Cat’s claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat’s claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat’s claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha 532B 53B 534B 53B 536B 36 production. The primary mechanism for cat’s claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis. PMID: 10962207 [PubMed - indexed for MEDLINE] 16. Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis. Miller MJ, Angeles FM, Reuter BK, Bobrowski P, Sandoval M. Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. [email protected] BMC Complement Altern Med. 2001;1(1):11. Epub 2001 Dec 10 BACKGROUND: The potential of ascorbic acid and two botanical decoctions, green tea and cat’s claw, to limit cell death in response to oxidants were evaluated in vitro. METHODS: Cultured human gastric epithelial cells (AGS) or murine small intestinal epithelial cells (IEC-18) were exposed to oxidants DPPH (3 microM), H2O2 (50 microM), peroxynitrite (300 microM) - followed by incubation for 24 hours, with antioxidants (10 microg/ml) administered as a 1 hour pretreatment. Cell number (MTT assay) and death via apoptosis or necrosis (ELISA, LDH release) was determined. The direct interactions between antioxidants and DPPH (100 microM) or H2O2 (50 microM) were evaluated by spectroscopy. RESULTS: The decoctions did not interact with H2O2, but quenched DPPH although less effectively than vitamin C. In contrast, vitamin C was significantly less effective in protecting human gastric epithelial cells (AGS) from apoptosis induced by DPPH, peroxynitrite and H2O2 (P < 0.001). Green tea and cat’s claw were equally protective against peroxynitrite and H2O2, but green tea was more effective than cat’s claw in reducing DPPH-induced apoptosis (P < 0.01). Necrotic cell death was marginally evident at these low concentrations of peroxynitrite and H2O2, and was attenuated both by cat’s claw and green tea (P < 0.01). In IEC-18 cells, all antioxidants were equally effective as antiapoptotic agents. CONCLUSIONS: These results indicate that dietary antioxidants can limit epithelial cell death in response to oxidant stress. In the case of green tea and cat’s claw, the cytoprotective response exceed their inherent ability to interact with the injurious oxidant, suggestive of actions on intracellular pathways regulating cell death. PMID: 11749672 [PubMed - indexed for MEDLINE] 17. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Sheng Y, Li L, Holmgren K, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2001 Jul;8(4):275-82 The Uncaria tomentosa water extracts (C-Med-100) have been shown to enhance DNA repair, mitogenic response and leukocyte recovery after chemotherapy-induced DNA damage in vivo. In this study, the effect of C-Med-100 supplement was evaluated in a human volunteer study. Twelve apparently healthy adults working in the same environment were randomly assigned into 3 groups with age and gender matched. One group was daily supplemented with a 250 mg tablet containing an aqueous extract of Uncaria tomentosa of C-Med-100, and another group with a 350 mg tablet, for 8 consecutive weeks. DNA repair after induction of DNA damage by a standard dose of hydrogen peroxide was measured 3 times before supplement and 3 times after the supplement for the last 3 weeks of the 8 week-supplement period. There were no drug-related toxic responses to C-Med-100 supplement when judged in terms of clinical symptoms, serum clinical chemistry, whole blood analysis and leukocyte differential counts. There was a statistically significant decrease of DNA damage and a concomitant increase of DNA repair in the supplement groups (250 and 350 mg/day) when compared with non-supplemented controls (p < 0.05). There was also an increased tendency of PHA induced lymphocyte proliferation in the treatment groups. Taken together, this trial has confirmed the earlier results obtained in the rat model when estimating DNA repair enhancement by C-Med-100. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11515717 [PubMed - indexed for MEDLINE] 37 18. Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test. Mohamed AF, Matsumoto K, Tabata K, Takayama H, Kitajima M, Watanabe H. Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan. The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the antiamnesic effect of uncarine E. PMID: 11197086 [PubMed - indexed for MEDLINE] 51B 52B 53B 54B 5B 19. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa. Sheng Y, Bryngelsson C, Pero RW. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] J Ethnopharmacol. 2000 Feb;69(2):115-26. Female W/Fu rats were gavaged daily with a water-soluble extract (C-MED-100) of Uncaria tomentosa supplied commercially by CampaMed at the doses of 0, 5, 10, 20, 40 and 80 mg/kg for 8 consecutive weeks. Phytohemagglutinin (PHA) stimulated lymphocyte proliferation was significantly increased in splenocytes of rats treated at the doses of 40 and 80 mg/kg. White blood cells (WBC) from the C-MED100 treatment groups of 40 and 80 mg/kg for 8 weeks or 160 mg/kg for 4 weeks were significantly elevated compared with controls (P < 0.05). In a human volunteer study, C-MED-100 was given daily at 5 mg/kg for 6 consecutive weeks to four healthy adult males. No toxicity was observed and again, WBC were significantly elevated (P < 0.05) after supplement. Repair of DNA single strand breaks (SSB) and double strand breaks (DSB) 3 h after 12 Gy whole body irradiation of rats were also significantly improved in C-MED-100 treated animals (P < 0.05). The LD50 and MTD of a single oral dose of CMED-100 in the rat were observed to be greater than 8 g/kg. Although the rats were treated daily with U. tomentosa extracts at the doses of 10-80 mg/kg for 8 weeks or 160 mg/kg for 4 weeks, no acute or chronic toxicity signs were observed symptomatically. In addition, no body weight, food consumption, organ weight and kidney, liver, spleen, and heart pathological changes were found to be associated with C-MED-100 treatment. PMID: 10687868 [PubMed - indexed for MEDLINE] 56B 57B 58B 59B 560B 561B 20. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa. Sheng Y, Pero RW, Wagner H. 562B 563B 38 Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2000 Apr;7(2):137-43. The Uncaria tomentosa water extracts (C-Med-100) depleted of indole alkaloids (< 0.05%, w/w) have been shown to induce apoptosis and inhibit proliferation in tumor cells in vitro and to enhance DNA repair, mitogenic response and white blood cells in vivo. In this study, the effect of C-Med-100 in the treatment of chemically induced leukopenia was evaluated in a rat model. W/Fu rats were treated first with doxorubicin (DXR) 2 mg/kg x 3 (i.p. injection at 24 hour-intervals) to induce leukopenia. Twentyfour hours after the last DXR treatment, the rats were daily gavaged with C-Med-100 for 16 consecutive days. As a positive control, Neupogen, a granulocyte colony stimulator was also administered by subcutaneous injection at a dose of 5 and 10 microg/ml for 10 consecutive days. The results showed that both C-Med-100 and Neupogen treatment groups recovered significantly sooner (p < 0.05 by Duncan test) than DXR group. However, the recovery by C-Med-100 treatment was a more natural process than Neupogen because all fractions of white blood cells were proportionally increased while Neupogen mainly elevated the neutrophil cells. These results were also confirmed by microscopic examination of the blood smears. The mechanism of the C-Med-100 effect on WBC is not known but other data showing enhanced effects on DNA repair and immune cell proliferative response support a general immune enhancement. PMID: 10839217 [PubMed - indexed for MEDLINE] 21. Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100. Lamm S, Sheng Y, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. Phytomedicine. 2001 Jul;8(4):267-74 A human intervention study was carri ed out using male volunteers attending a General Practice Clinic in New York City involving comparison of individuals supplemented with 350 mg x 2 C-Med-100 daily dose for two months with untreated controls for their abilities to respond to a 23 valent pneumococcal vaccine. C-Med-100 is a novel nutraceutical extract from the South American plant Uncaria tomentosa or Cat’s Claw which is known to possess immune enhancing and antiinflammatory properties in animals. There were no toxic side effects observed as judged by medical examination, clinical chemistry and blood cell analysis. However, statistically significant immune enhancement for the individuals on CMed-100 supplement was observed by (i) an elevation in the lymphocyte/neutrophil ratios of peripheral blood and (ii) a reduced decay in the 12 serotype antibody titer responses to pneumococcal vaccination at 5 months. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11515716 [PubMed - indexed for MEDLINE] 22. In vitro Effects of Two Extracts and Two Pure Alkaloid Preparations of Uncaria tomentosa on Peripheral Blood Mononuclear Cells. Winkler C, Wirleitner B, Schroecksnadel K, Schennach H, Mur E, Fuchs D. Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria. Planta Med. 2004 Mar;70(3):205-10. In the traditional Peruvian medicine, hot aqueous extracts of Uncaria tomentosa have been used for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. Some of the beneficial effects observed in patients suggest an immunomodulatory capacity of Uncaria tomentosa extracts. In this study, the effects of two extracts and two mixtures of tetracyclic and pentacyclic oxindole alkaloids of Uncaria tomentosa were investigated in freshly isolated human peripheral blood mononuclear cells (PBMC) stimulated with the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) in vitro. Neopterin production and tryptophan degradation were monitored in culture supernatants to determine the effects of the test substances on immunobiochemical pathways induced by 39 interferon-gamma. Compared to unstimulated cells PHA and Con A increased the production of neopterin and degradation of tryptophan (p < 0.01). HCl and ethanol extracts and mixtures of alkaloids of Uncaria tomentosa inhibited both effects in a dose-dependent manner, the lowest effective concentrations of the extracts were 500 - 1000 microg/mL and of the alkaloid mixtures 100 - 175 microg/mL (p < 0.05 and < 0.01). With the highest concentrations of extracts and mixtures complete suppression of mitogen-induced neopterin production and tryptophan degradation was observed. These data demonstrate that Uncaria tomentosa extracts and mixtures of alkaloids modulate the immunobiochemical pathways induced by interferon-gamma. The findings imply a potential application of the extracts as immunoregulators and would be in line with observations in patients using these extracts. Abbreviations. Con A:concanavalin A EDTA:ethylenediaminetetraacetic acid, Titriplex III IDO:indoleamine (2,3)-dioxygenase IFN-gamma:interferon-gamma kyn:kynurenine MTT:3-(4,5dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide PBMC:peripheral blood mononuclear cells PHA:phytohaemagglutinin POA:pentacyclic oxindole alkaloids ROS:reactive oxygen species TOA:tetracyclic oxindole alkaloids trp:tryptophan PMID: 15114496 [PubMed - in process] 580B OTHER RESEARCH: 581B There are two species of Cat's Claw, Uncaria tomentosa and Uncaria guianensis, each having different properties and uses. The two are frequently confused but U. tomentosa is the more heavily researched for medicinal use[2] and immune modulation, while U. guianensis may be more useful for osteoarthritis.[3] U. tomentosa is further divided into two chemotypes with different properties and active compounds, a fact ignored by most manufacturers[4] that can have significant implications on both its use as an alternative medicine and in clinical trials to prove or disprove its efficacy.[5] 582B Medicinal uses The parts used medicinally include the inner bark and root, taken in the form of capsules, tea and extract. 583B 584B U. tomentosa is used in nootropic drugs, as well as in treatment of cancer and HIV infection. It contains several alkaloids that are responsible for its overall medical effects, as well as tannins and various phytochemicals.[6] The chemotype of the plant determines the dominant type of alkaloid it produces, and thus its properties in vivo. One chemotype has roots which produce mostly the pentacyclic alkaloids that are responsible for the immunestrengthening effects desired by most consumers. The second chemotype produces tetracyclic oxindole alkaloids known as rhynchophylline and isorhynchophylline which counteract the immune-strengthening actions of the pentacyclic alkaloids, reduces the speed and force of the heart's contraction, and in high doses produce ataxia, lack of coordination and sedative effects.[5] Since U. tomentosa comes in at least these two different chemotypes, without chemical testing it is impossible to know which chemical compounds will predominate in a plant collected randomly from a natural setting. 58B Some ingredients appear to act as anti-inflammatory, antioxidant and anticancer agents.[6] As an herbal treatment, Cat's Claw is used to treat intestinal ailments such as Crohn's disease, gastric ulcers and tumors, parasites, colitis, gastritis, diverticulitis and leaky bowel syndrome, while manufacturers claim that U. tomentosa can also be used in the treatment of AIDS in combination with AZT, the treatment and prevention of arthritis and rheumatism, diabetes, PMS, chronic fatigue syndrome, prostate conditions,[7] immune modulation,[8] Lyme disease[9] and systemic lupus erythematosus.[10] A 2005 review of the scholarly literature on Cat's Claw indicates there is supporting evidence toward its use in treating cancer, inflammation, viral infection and vascular conditions, and for its use as an immunostimulant, antioxidant, antibacterial and CNSrelated agent.[6] 586B 587B It has also been shown to be a powerful MAO-B inhibitor. [11] 40 Indigenous use The indigenous peoples of South and Central America have used U. tomentosa for medicinal purposes for two thousand years or more, It is often added to Ayahuasca. Researchers have investigated the use of the plant by the Asháninka tribe of Peru, who use the plant as a general health tonic, contraceptive, anti-inflammatory agent for the gastrointestinal tract, and as a treatment for diarrhea, rheumatic disorders, acne, diabetes, cancer and diseases of the urinary tract.[12] In Brazilian traditional medicine it is used against dengue to reduce inflammation and DOES NOT prevent dengue.[13] Allergies Individuals allergic to plants in the Rubiaceae family and different species of Uncaria may be more likely to have allergic reactions to Cat's Claw.[14] Reactions can include itching, rash and allergic inflammation of the kidneys. In one documented case, kidney failure occurred in a patient with Lupus erythematosus[15] but it is not known if this was due to an allergic reaction or another cause. There are other plants which are known as cat's claw (or uña de gato) in Mexico and Latin America; however, they are entirely different plants, belonging to neither the Uncaria genus, nor to the Rubiaceae family. Some of the Mexican uña de gato varieties are known to have toxic properties. Footnotes 1. "Species Information". sun.ars-grin.gov. http://sun.arsgrin.gov:8080/npgspub/xsql/duke/plantdisp.xsql?taxon=1972. Retrieved on 2008-03-01. 2. Gattuso, M., Di Sapio, O., Gattuso, S. & Li Pereyra, E. (2004). Morphoanatomical studies of Uncaria tomentosa and Uncaria guianensis bark and leaves. Phytomedicine, 11, 213–223. 3. Piscoya J, Rodriguez Z, Bustamante SA, et al. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001;50:442–448. 4. Keplinger, K., Laus, G., Wurm, M., Dierich, M.P. & Teppner, Herwig. (1999). Uncaria tomentosa (Willd.) DC.—Ethnomedicinal use and new pharmacological, toxicological and botanical results. Journal of Ethnopharmacology, 64, 23–34. Available on-line as a PDF 5. ab 6. abc Nutrition Forum article by Varro E. Tyler on Cat's Claw Heitzman, M.E., Neto, C.C., Winiarz, E., Vaisberg, A.J. & Hammon, G.B. (2005). Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry, 66(1), 5-29. PMID 15649507 7. NutraSanus article on Cat's Claw 8. Information on Cat's Claw 9. Treatment of Lyme disease with Cat's Claw 10. Cat's claw used to treat Lupus erythematosus 11. [1] ^ The Longwood Herbal Task Force article on Cat's Claw 12. [2] ^ Intelihealth article discussing uses and dangers of Cat's Claw 13. Hilepo JN, Bellucci AG, Mossey RT. (1977). Acute renal failure caused by 'cat's claw' herbal remedy in a patient with systemic lupus erythematosus. Nephron, 77(3) pg. 361. 41 14. References 607B 15. Germplasm Resources Information Network: Uncaria tomentosa 608B 16. External links 609B 17. Webpage on Cat's Claw with a library of scientific abstracts organized by year 610B 18. Uncaria tomentosa List of Chemicals (Dr. Duke's Databases) 61B UNIVERSITY OF MARYLAND MEDICAL CENTER RESEARCH: 612B Named after its hook-like horns, cat's claw (Uncaria tomentosa) is a woody vine native to the Amazon rainforest and other tropical areas of South and Central America. The bark and root of this herb have been used by South Americans since the Inca civilization to treat a variety of health problems, including arthritis, stomach ulcers, inflammation, dysentery, and fevers. It was also used as a form of birth control. Test tube studies indicate that cat's claw may stimulate the immune system, help relax the smooth muscles (such as the intestines), dilate blood vessels (helping lower blood pressure), and act as a diuretic (helping rid the body of excess water). It also has antioxidant properties, helping rid the body of particles known as free radicals that damage cells. Preliminary studies show it may have antitumor and anticancer effects as well. 613B 614B Osteoarthritis Although few scientific studies have investigated the safety and usefulness of this herb, it has been used traditionally to treat osteoarthritis (OA). One study indicates that it may help relieve pain from knee OA without side effects. 615B 61B Rheumatoid arthritis Cat's claw has been suggested as a treatment for rheumatoid arthritis (RA) because of its anti-inflammatory properties. One small study showed a positive effect when cat's claw was taken by people who were also taking sulfasalazine or hydroxychloroquine to treat RA. Although cat's claw may help reduce inflammation, there is no evidence to show that it stops the progression of the disease. For that reason, RA should be treated with conventional medications, which can put the disease into remission. 617B 618B Further research Cat's claw is being studied for a number of other possible uses, including HIV, Chron's disease, multiple sclerosis, systemic lupus erythematosus (SLE or lupus), and Alzheimer's disease. More research is needed before scientists can say whether it is effective. 619B 620B Plant Description: Cat's claw is a thorny vine that can climb as high as 100 feet. It grows primarily in the Amazon rainforest as well as tropical areas in South and Central America. Much of the cat's claw sold in the United States was grown in Peru. Cat's claw got its name from the curved, claw-like thorns that grow on its stem. The root and bark of cat's claw are the parts used for medicinal purposes. 621B 62B 623B What's It Made Of?: Cat's claw contains many types of plant chemicals that help reduce inflammation (such as tannins and sterols) and combat certain viruses (such as quinovic acid glycosides). Cat's claw preparations are made from the root and bark of the cat's claw vine. The effectiveness of the root and bark varies depending upon what time of year that portion of the plant is harvested. 624B 625B 62B 42 Available Forms: The bark of the cat's claw vine can be crushed and used to make tea. Standardized root and bark extracts (containing 3% alkaloids and 15% phenols) are also available in either liquid or capsule forms. How to Take It: Pediatric There are no known scientific reports on the pediatric use of cat's claw. Do not give a child cat's claw without the supervision of your doctor. Adult Dry, encapsulated standardized extract: 100 mg per day for osteoarthritis; 250 - 350 mg per day for immune support Precautions: The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, you should take herbs with care, under the supervision of a health care practitioner. Cat's claw appears to have few side effects. However, there have not been enough scientific studies of cat's claw to fully determine its safety. Some people have reported dizziness, nausea, and diarrhea when taking cat's claw. The diarrhea or loose stools tend to be mild and go away with continued use of the herb. Cat's claw may cause miscarriage and should not be taken by pregnant or nursing women. People with autoimmune diseases, skin grafts, tuberculosis, or those receiving organ transplants should not use cat's claw because of its possible effects on the immune system. Possible Interactions: If you are currently taking any of the following medications, you should not use cat's claw without first talking to your health care provider. Immunosuppressive medications -- In theory, because cat's claw may stimulate the immune system, it should not be used with medications intended to suppress the immune system, such as cyclosporin or other medications prescribed following an organ transplant or to treat an autoimmune disease. NSAIDs -- Cat's claw may protect against gastrointestinal damage associated with nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin) and naproxen (Aleve). Other medications -- Cat's claw may interact with the following medications: Anticoagulants (blood-thinning medication) Diuretics (water pills) Estrogens or progestins, including birth control pills Antihypertensive (blood pressure) medication Alternative Names: Una de gato; Uncaria tomentosa Reviewed last on: 11/11/2008 1. Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network. 2. Supporting Research 3. Aquino R, De Feo V, De Simone F, et al. New compounds and anti-inflammatory activity of Uncaria tomentosa. J Nat Prod. 1991;54: 453-459. 43 4. Gonzales GF, Valerio LG. Medicinal plants from Peru: a review of plants as potential agents against cancer. Anticancer Agents Med Chem. 2006;6(5):429-44. 653B 5. Hardin SR. Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007 Feb;13(1):25-8. 654B 6. Karch SB. The Consumer's Guide to Herbal Medicine. Hauppauge, New York: Advanced Research Press; 1999:55-56. 65B 7. Keplinger K, Laus G, Wurm M, et al. Uncaria tomentosa (Willd.) Dethnomedicinal use and new pharmacological, toxicological and botanical results. J Ethnopharmacol. 1999;64:23-34. 65B 8. Lemaire I, Assinewe V, Cano P, et al. Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa. J Ethnopharmacol. 1999;64:109-115. 657B 9. Mur E, Hartig F, Eibl G, et al. Randomized double blind trial of an extract from the pentacyclic alkaloidchemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002 Apr;29(4):678-81. 658B 10. Pilarski R, Zielinski H, Ciesiolka D, et al. Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC. J Ethnopharmacol. 2006 Mar 8;104(1-2):18-23. 659B 11. Piscoya J, Rodriguez Z, Bustamante SA, et al. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001;50(9):442-448. 60B 12. Rizzi R, Re F, Bianchi A, et al. Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. J Ethnopharmacol. 1993;38(1):63-77. 61B 13. Rotblatt M, Ziment I. Evidence-Based Herbal Medicine. Philadelphia, PA: Hanley & Belfus, Inc; 2002:114-118. 62B 14. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med. 2000;29(1):71-78. 63B 15. Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Semin Arthritis Rheum. 2005 Jun;34(6):773-84. Review. 64B 16. Sheng Y, et al. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Anticancer Res. 1998;18:3,363-3,368. 65B 17. Sheng Y, Pero RW, Wagner H. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa. Phytomedicine. 2000;7(2):137-143. 6B 18. Spelman K, Burns J, Nichols D, et al. Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators. Altern Med Rev. 2006 Jun;11(2):128-50. Review. 67B 19. Steinberg PN. Cat's claw: medicinal properties of this Amazon vine. Nutrition Science News. 1995. 68B 44 ADDITONAL RESEARCH: 1. Medical Botany, Lewis et al., published 1977 by John Wiley & Sons (NY), pp 277-279 and 509.* . 2. Mark JS Miller et al., Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis, BMC Comp and Alternative Med Dec. 2001, I:II, U.S. . 3. M. Sandoval et al., Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are indept . . . , Phytomedicine 9:325-337, 2002, U.S. . 4. J Piscoya et al., Efficacy and safety of freeze-dried cat's claw in osteorarthritis of the knee: mechanisms . . . , Inflamm.res.50(2001) 442-448, U.S. . 5. M Sandoval et al., Cat's Claw Inhibits TNalpha Prod. and Scavenges Free Radicals: Role in Cytoprotection, Free Radical Biology & Med, vol. 29 No. 1 pp 71-78,2000, U.S. . 6. R Aquino et al, New quinovic acid glycosides from Uncaria Tomentosa, J Natural Prod, vol. 51, No. 2, pp 257-261, Mar.-Apr. 1998, U.S. . 7. G Konwalinka, Capillary electrophoretic analysis of oxidole alkaloids from Uncaria tomentosa, J of Chromatography, 609 (1992) pp 375-380, U.S. . 8. H Stuppner et al, HPLC Analysis of the Main Oxidole Alkaloids from Uncaria tomentosa, Chromatography, V 34, No 11/12, Dec. 1992, U.S. . 9. G. Laus et al., Separation of Stereoisomeric oxidole alkaloids from Uncaria tomentosa by high performance liquid chromatography, J Chromatography, A, 662 (1994) U.S. . 10. Y Sheng et al, Induction of Apoptosis and Inhibition of Proliferation of Human Tumor Cells Treated with Extracts of Uncaria Tomentosa, Anticancer Research 18:3363-3368 (1998). . 11. M Sandoval-Chacon, Antiinflammatory actions of cat's claw: the role of NF-.kappa.B, Aliment Pharmacol Ther 1998;12;1279-1289 U.S. . 12. K Keplinger et al, Uncaria tomentosa (Willd.) DC.-Ethnomedicinal use and new pharmacological, toxicological and botanical results, J Ethnopharmacology 64 (1999) 23-34 U.S. . 13. Y Sheng et al, Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa, J Ethnopharmacology 69 (2000) 115-126 US. . 14. S Lamm, Persistant response to pneumococcal vaccine in individuals supplemented with a novel water soluable extract of Uncaria tomentosa, C-MED-100.RTM. Phytomedicine, vol. 8(4) pp. 267-274 U.S., no date provided. THE UNIVERSITY OF TEXAS CENTER FOR ALTERNATIVE MEDICINE RESEARCH: (UT-CAM) CATS CLAW Other Common Names: Una de gato, Uncaria tomentosa Range: South and Central America, Andes mountains, particularly in Peru. Habitat: Rain forest. The Spanish name for it is "Una de gato". The name comes from the claw like features of the plant vines that resemble cat's claws. The inner bark of the vine is thought to contain the medicinal properties and therefore, is 45 used to treat the following conditions: arthritis, gastritis, asthma, gastric ulcer, diabetes, cancer and tumors, viral infections, menstrual disorders, convalescence, rheumatism, general debility, gonorrhea, stimulate the immune system, and to promote wound healing. According to Ramon Ferreyra, Ph.D., a Harvard-educated botanist and professor at San Marcos University in Lima, Peru and the President of the Peruvian Botanical Society, states that twelve herbs in Peru are identified as Una de gato or cat’s claw. The herb of primary interest to alternative medicine researchers is Uncaria tomentosa, a woody vine that grows 1100 feet or more. The active constituents of Uncaria tomentosa may be a group of alkaloids with immune stimulating activity. Recent reports have demonstrated Uncaria’s role in improving immunity in cancer patients as well as its antimutagenic properties. All the individual alkaloids of Uncaria tomentosa with the exception of rynchophylline and mitraphylline have immunostimulant properties and the ability to enhance phagocytosis in vitro. Cat's claw is available as a tincture, capsules, tablets, elixirs, and as a cream. It may also be used as a tea. It can also be found mixed with other herbal therapies such as aloe. Known Hazards: This product should not be taken if you have an autoimmune disease, multiple sclerosis, or tuberculosis. In Europe, health care providers avoid combining this herb with hormonal drugs, insulin, or vaccines. Do not take this product if you are pregnant or breast-feeding. Cat's claw may block platelets from forming clots, so you should be cautious if you are already taking a medication, including aspirin, which thins the blood. A word of caution for the prospective buyers of cat’s claw: another plant also known as cat’s claw, (botanical name-Acacia gregii), grows along the Northern Mexico and Southern Texas border. People are purchasing this plant mistakenly believing it to be the Peruvian medicinal plant. This plant may be poisonous and is thought to contain a cyanide-based chemical compound. The Peruvian cat’s claw has a cinnamon colored bark; whereas, the South Texas plant comes from a shrub and so contains little twigs and leaves. The University of Texas Center for Alternative Medicine Research (UT-CAM) 690B 691B 692B 693B 694B 695B PUBMED/MEDLINE SUPPLEMENTAL RESEARCH 69B Cat’s Claw acts as an immune stimulant and an adjunctive therapy for cancer (to reduce side effects of chemotherapy and protect cells); as a bowel cleanser and anti-inflammatory for Crohn's, colitis, diverticulitis, irritable bowel syndrome (IBS), and other bowel problems; as an anti-inflammatory for arthritis (all kinds) and muscle pains/strains/injuries; as a general daily tonic (to tone, balance, and strengthen all body functions); for stomach ulcers and ulcerative colitis and as an ulcer preventative/ stomach and bowel protector) 697B Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJ, Sandoval M. Universidad Nacional Mayor de San Marcos, Facultad de Medicina, Lima, Peru. AIM: The purpose of this investigation was to evaluate the ability of cat's claw, an Amazonian medicinal plant, to treat osteoarthritis of the knee, collect safety and tolerance information and compare the antioxidant, and antiinflammatory actions of Uncaria guianensis and Uncaria tomentosa in vitro. MATERIALS AND METHODS: Forty-five patients with osteoarthritis of the knee were recruited, 30 were treated with freeze-dried U guianensis, and 15 with placebo. Hematological parameters were assessed on entry and exit of the four-week trial. Pain, medical and subject assessment scores and adverse effects were collected at weeks 1, 2 and 4. The antioxidant and anti-inflammatory activity of the cat's claw species was determined by the alpha,alphadiphenyl-beta-picrylhydrazyl (DPPH) free radical scavenging method. Inhibition of TNFalpha and prostaglandin E2 (PGE2) production was determined in RAW 264.7 cells by ELISA. RESULTS: Cat's claw had no deleterious effects on blood or liver function or other significant side-effects compared to placebo. Pain associated with activity, medical and patient assessment scores were all significantly reduced, with benefits occurring within the first week of therapy. Knee pain at rest or at night, and knee circumference were not significantly reduced by cat's claw during this brief trial. In vitro tests indicated that U guianensis and U. tomentosa were equivalent at quenching DPPH radicals (EC50, 13.6-21.7 microg/ml) as well as inhibiting TNFalpha production. However, the latter action was registered at much lower concentrations (EC50, 10.2-10.9 ng/ml). Cat's claw (10 microg/ml) had no effect on basal PGE2 production, but reduced LPS-induced PGE2 698B 69B 70B 46 release (P < 0.05), but at higher concentrations than that required for TNFalpha inhibition. CONCLUSION: Cat's claw is an effective treatment for osteoarthritis. The species, U guianensis and U tomentosa are equiactive. They are effective antioxidants, but their anti-inflammatory properties may result from their ability to inhibit TNFalpha and to a lesser extent PGE2 production. PMID: 11603848 [PubMed - indexed for MEDLINE] Related articles Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002 May; 9(4):325-37. [Phytomedicine. 2002] Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med. 2000 Jul 1; 29(1):71-8. [Free Radic Biol Med. 2000] ReviewCat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007 Feb; 13(1):25-8. Epub 2006 Dec 13. [Complement Ther Clin Pract. 2007] ReviewToxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii) : a critical synopsis. Toxicol Rev. 2005; 24(1):11-35. [Toxicol Rev. 2005] Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for antiinflammatory activity. Phytochemistry. 2005 Jan; 66(1):89-98. [Phytochemistry. 2005] » See reviews... | » See all... Cited by 5 PubMed Central articles Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. Mehta K, Gala J, Bhasale S, Naik S, Modak M, Thakur H, Deo N, Miller MJ. BMC Complement Altern Med. 2007 Oct 31; 7:34. Epub 2007 Oct 31. [BMC Complement Altern Med. 2007] ReviewOsteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Ameye LG, Chee WS. Arthritis Res Ther. 2006; 8(4):R127. [Arthritis Res Ther. 2006] The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta. Miller MJ, Ahmed S, Bobrowski P, Haqqi TM. BMC Complement Altern Med. 2006 Apr 7; 6:13. Epub 2006 Apr 7. [BMC Complement Altern Med. 2006] » See all... Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ. Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Cat's claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat's claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat's claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 47 microg/ml, p <.05). Cat's claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat's claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat's claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha production. The primary mechanism for cat's claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis. PMID: 10962207 [PubMed - indexed for MEDLINE] Related articles Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002 May; 9(4):325-37. [Phytomedicine. 2002] Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001 Sep; 50(9):442-8. [Inflamm Res. 2001] ReviewToxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii) : a critical synopsis. Toxicol Rev. 2005; 24(1):11-35. [Toxicol Rev. 2005] ReviewCat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007 Feb; 13(1):25-8. Epub 2006 Dec 13. [Complement Ther Clin Pract. 2007] Antiinflammatory actions of cat's claw: the role of NF-kappaB. Aliment Pharmacol Ther. 1998 Dec; 12(12):1279-89. [Aliment Pharmacol Ther. 1998] 73B 734B 735B 736B 73B 738B 739B 740B 741B 742B 743B 74B 745B 746B 74B 748B 749B Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Hardin SR. University of North Carolina at Charlotte, School of Nursing 750B 751B 752B Cat's claw (Uncaria tomentosa and Uncaria guianesis) is a medicinal plant from the Amazon commonly used to treat disorders such as arthritis, gastritis and osteoarthritis. The mechanism of cat's claw appears to be as an inhibitor of TNFalpha and antioxidant. Understanding the processes in osteoarthritis may facilitate and clarify the potential role of cat's claw as a complementary therapy to assist in the reduction of pro-inflammatory mediators and effectors. The clinical relevance of this therapy as a viable modality of intervention will be discussed. 753B Valerio LG Jr, Gonzales GF. Division of Biotechnology and GRAS Notice Review, Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, PMID: 16042502 [PubMed - indexed for MEDLINE] Recent exceptional growth in human exposure to natural products known to originate from traditional medicine has lead to a resurgence of scientific interest in their biological effects. As a strategy for improvement of the assessment of their pharmacological and toxicological profile, scientific evidence-based approaches are being employed to appropriately evaluate composition, quality, potential medicinal activity and safety of these natural products. Using this approach, we comprehensively reviewed existing scientific evidence for known composition, medicinal uses (past and present), and documented biological effects with emphasis on clinical pharmacology and toxicology of two commonly used medicinal plants from South America with substantial human exposure from historical and current global use: Uncaria tomentosa (common name: cat's claw, and 754B 75B 756B 48 Spanish: uña de gato), and Lepidium meyenii (common name: maca). Despite the geographic sourcing from remote regions of the tropical Amazon and high altitude Andean mountains, cat's claw and maca are widely available commercially in industrialised countries. Analytical characterisations of their active constituents have identified a variety of classes of compounds of toxicological, pharmacological and even nutritional interest including oxindole and indole alkaloids, flavonoids, glucosinolates, sterols, polyunsaturated fatty acids, carbolines and other compounds.The oxindole alkaloids from the root bark of cat's claw are thought to invoke its most widely sought-after medicinal effects as a herbal remedy against inflammation. We find the scientific evidence supporting this claim is not conclusive and although there exists a base of information addressing this medicinal use, it is limited in scope with some evidence accumulated from in vitro studies towards understanding possible mechanisms of action by specific oxindole alkaloids through inhibition of nuclear factor (NF)-kappaB activation. Although controlled clinical studies have demonstrated reduction in pain associated with cat's claw intake in patients with various chronic inflammatory disorders, there is insufficient clinical data overall to draw a firm conclusion for its anti-inflammatory effects. An important observation was that experimental results were often dependent upon the nature of the preparation used. It appears that the presence of unknown substances has an important role in the overall effects of cat's claw extracts is an important factor for consideration. The available animal toxicological studies did not indicate severe toxicity from oral intake of cat's claw preparations but rather were suggestive of a low potential for acute and subacute oral toxicity, and a lack of evidence to demonstrate genotoxic potential and mutagenic activity. Cat’s Claw has been widely studied as an anti-inflammatory, which has been attributed to its content of oxindolic alkaloids. These studies have been conducted in four hospitals in Peru: Lima, Callao, Ica and Huancayo, with 60 patients with classic Rheumatoid Arthritis. In a double blind test, 31 patients received 6 daily capsules of Cat’s Claw (Uncaria tomentosa) and another group of 29 patients received the same quantity of capsules containing a placebo. The study lasted 6 months, and they carried out an evaluation at the one month, three month and six month periods. The results revealed with stunning clarity that the patients who that Cat’s experienced a very significant improvement in morning stiffness, daily pain levels and a reduction in the number of inflamed joints. Pollen: 1. Natural Health Bible for Dogs and Cats, Messonier, Shawn DVM 2. Herbal Healing for Pets. The Herbal Encyclopedia 3. Aliyazicioglu Y, Deger O, Ovali E, et al. Effects of Turkish pollen and propolis extracts on respiratory burst for K-562 cell lines. Int Immunopharmacol 2005;5(11):1652-1657. 4. Boppre M, Colegate SM, Edgar JA. Pyrrolizidine alkaloids of Echium vulgare honey found in pure pollen. J Agric Food Chem 2005;53(3):594-600. 5. Campos MG, Webby RF, Markham KR, et al. Age-induced diminution of free radical scavenging capacity in bee pollens and the contribution of constituent flavonoids. J Agric Food Chem 2003;51(3):742-745. 6. Garcia-Villanova RJ, Cordon C, Gonzalez Paramas AM, et al. Simultaneous immunoaffinity column cleanup and HPLC analysis of aflatoxins and ochratoxin A in Spanish bee pollen. J Agric Food Chem 2004;52(24):7235-7239. 7. Gonzalez G, Hinojo MJ, Mateo R, et al. Occurrence of mycotoxin producing fungi in bee pollen. Int J Food Microbiol 2005;105(1):1-9. 8. Greenberger PA, Flais MJ. Bee pollen-induced anaphylactic reaction in an unknowingly sensitized subject. Ann Allergy Asthma Immunol 2001;86(2):239-242. 49 9. Iarosh AA, Macheret EL, Iarosh AA, et al. [Changes in the immunological reactivity of patients with disseminated sclerosis treated by prednisolone and the preparation Proper-Myl]. Vrach Delo 1990;(2):83-86. 769B 10. Iversen T, Fiirgaard KM, Schriver P, et al. The effect of NaO Li Su on memory functions and blood chemistry in elderly people. J Ethnopharmacol 1997;56(2):109-116. 70B 11. Krivopalov-Moscvin I. Apitherapy in the rehabilitation of patients with multiple sclerosis -- XVI World Congress of Neurology. Buenos Aires, Argentina, September 14-19, 1997. Abstracts. J Neurol Sci 1997;150 Suppl:S264-367. 71B 12. Lei H, Shi Q, Ge F, et al. [Supercritical CO2 extraction of fatty oils from bee pollen and its GC-MS analysis]. Zhong Yao Cai 2004;27(3):177-180. 72B 13. Medina A, Gonzalez G, Saez JM, et al. Bee pollen, a substrate that stimulates ochratoxin A production by Aspergillus ochraceus Wilh. Syst Appl Microbiol 2004;27(2):261-267. 73B 14. Ozcan M, Unver A, Ceylan DA, et al. Inhibitory effect of pollen and propolis extracts. Nahrung 2004;48(3):188-194. 74B 15. Palanisamy A, Haller C, Olson KR. Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen. J Toxicol Clin Toxicol 2003;41(6):865-867. 75B 16. Paola-Naranjo RD, Sanchez-Sanchez J, Gonzalez-Paramas AM, et al. Liquid chromatographic-mass spectrometric analysis of anthocyanin composition of dark blue bee pollen from Echium plantagineum. J Chromatogr A 2004;1054(1-2):205-210. 76B 17. Wang J, Jin GM, Zheng YM, et al. [Effect of bee pollen on development of immune organ of animal]. Zhongguo Zhong Yao Za Zhi 2005;30(19):15327B 18. Steben RE, Boudreaux P. The effects of pollen and protein extracts on selected blood factors and performance of athletes. J Sports Med 1978;18:221-6. 78B 19. Small randomized study evaluating the effect of bee pollen supplement on 18 male high school students. Three treatment arms were established to compare bee pollen to protein extract to placebo. Following 12 weeks of training and supplementation, no effect of the bee pollen, protein extract, or placebo was seen on performance, hemoglobin, or serum electrolytes. This small study was probably incapable of detecting a statistically significant difference between treatment groups. No adverse events were reported with supplementation. 79B References 1. Mirkin G. Can bee pollen benefit health? JAMA 1989;262:1854. 780B 781B 2. DerMarderosian A, editor. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999. 782B 3. Maughan RJ, Evans SP. Effects of pollen extract upon adolescent swimmers. Br J Sports Med. 1982 Sep;16(3):142-5. 783B 4. Steben RE, Boudreaux P. The effects of pollen and protein extracts on selected blood factors and performance of athletes. J Sports Med Phys Fitness. 1978;18:221-6. 784B 5. Palanisamy A, Haller C, Olson KR. Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen. J Toxicol Clin Toxicol. 2003;41(6):865-7. 785B 50 Read more: http://www.healthline.com/natstandardcontent/bee-pollen/3#ixzz1CCiHgS1V Read more: http://www.healthline.com/natstandardcontent/bee-pollen#ixzz1CChJ4ENe Natural Treatment for Grass Allergies in Dogs. eHow.com http://aliveinthehive.blogspot.com alpented.wordpress.com/2011/01/17/bee-pollen-for-pets/ Bee Pollen: A Nutritious Part of Your Dogs’ Diet. Alicia McWatters, Ph.D., C.N.C. Bee Pollen For Dogs.www.411-for-dogs.com/bee-pollen-for-dogs.html Bee Pollen Dogs. hubpages.com/hub/Bee-Pollen-Dogs Bee Pollen For Cats and Dogs. www.cattearoom.com/uncategorized/bee-pollen-for-cats-and-dogs/ Annatto: 1. Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes mellitus. Lans CA. PMID: 17040567 [PubMed - in process] 2. Relative inhibition of lipid peroxidation, cyclooxygenase enzymes, and human tumor cell Reddy MK, Alexander-Lindo RL, Nair MG. PMID: 16277432 [PubMed - indexed for MEDLINE] 3. Antigenotoxic and antimutagenic potential of an annatto pigment (norbixin) against oxidative stress. Junior AC, Asad LM, Oliveira EB, Kovary K, Asad NR, Felzenszwalb I. PMID: 15841440 [PubMed indexed for MEDLINE] 4. Arkcoll, D. 1990. New crops from Brazil. In: J. Janick and J.E. Simon, eds.Advances in new crops. Timber press, Portland, OR. p. 367-371. 5. Baelmans R, Deharo E, Bourdy G, Muñoz V, Quenevo C, Sauvain M, Ginsburg H. A search for natural bioactive compounds in Bolivia through a multidisciplinary approach; Part IV. Is a new haem polymerisation inhibition test pertinent for the detection of antimalarial natural products?, Journal of Ethnopharmacology 2000; 73; 271-275 6. Bailey, L.H. 1941. The standard cyclopedia of horticulture. Vol. 1. The MacMillan Co. New York, NY. 1,200 p.Bruggeman, L. 1957. Tropical Plants and Their Cultivation. New York: 157, plate [222]. 7. Bressani, R., et al. "Chemical composition, amino acid content and nutritive value of the protein of the annatto seed (Bixa orellana L.)." Arch. Latinoam. Nutr. 33(2): 356-76. 8. Caceres A, Menendez H, Mendez E, Cohobon E, Samayoa BE, Jauregui E, Peralta E, Carrillo, G. Antigonorrhoeal Activity of Plants Used in Guatemala for the Treatment of Sexually Transmitted Diseases. Journal of Ethnopharmacology, 1995; 48: 85-88. 9. Cáceres A., et al. "Antigonorrhoeal activity of plants used in Guatemala for the treatment of sexually transmitted diseases." J. Ethnopharmacol. (October 1995). 10. Campelo, C. R. "Contribuicao ao estudo das plantas medicinais no estado de alagoas III, VII." Simposio de Plantas Medicinais do Brasil, 1-3 de Setembro, 1982, Belo Horizonte-MG, 85m. 11. Chopra, R. N. 1949. Poisonous Plans of India. Delhi, India: 203-210. Codex Alimentarius Commission. Codex Alimentarius Volume XIV. Food Additives. First Edition. Food and Agriculure Organization of the United Nations of the World Health Organization. 12. Di Mascio, P. "Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers." Biochem. Soc. Trans. 18 (1990): 1054-6. 51 13. Dunham, N. W. et al. "A preliminary pharmacologic investigation of the roots of Bixa orellana." J. Amer. Pharm. Ass. Sci. Ed. 1960; 49: 218. Faso. Journal of Food Composition and Analisys 1997; 10: 205-217. 80B 14. Fernandez-Ramos, C., F. Luque, C. Fernandez-Becerra, A. Osuna, S. Jankevicius, J. Jankevicius, M. Rosales & M. Sanchez-Moreno. 1999. Biochemical characterisation of flagellates isolated from fruits and seeds from Brazil. Fems Microbiology Letters. 170 (2): 343-348. 809B 15. Frega, N., M. Mozzon, & F. Bocci.1998. Identification and estimation of tocotrienols in the annatto lipid fraction by gas chromatography mass spectrometry. Journal of the American Oil Chemists Society. 75 (12): 1723-1727. 810B 16. Fregert S & Hjorth N (1969) Results of standard patch tests with substances abandoned. Contact Dermatitis Newsletter (5): 85-86 81B 17. Freise FW (1936) Vergiftungen durch Brasilianische Werkhölzer I. Sammlung von Vergiftungsfällen 7(1): C1-C8. 812B 18. Freixa, B., R. Vila, L. Vargas, N. Lozano, T. Adzet & S. Canigueral.1998. Screening for Antifungal Activity of Nineteen Latin American Plants. Phytotherapy Research.12(6): 427-430. 813B 19. George, M., et al. "Investigations on plant antibiotics. Part IV. Further search for antibiotic substances in Indian medicinal plants." Indian J. Med. Res. 1949; 37:169-81. 814B 20. Glew RH, VanderJagt DJ, Lockett C, Grivetti LE, Smith GC, Pastuszyn A, Millson M. Amino acid, fatty acid, and mineral composition of 24 indigenous plants of Burkina 815B 21. Haberli, A. & H. Pfander. 1999. Synthesis of bixin and three minor carotenoids from annato (Bixa orellana). Helvetica Chemica Acta.82 (5): 696-706. 816B 22. Hirose, S. "Energized state of mitochondria as revealed by the spectral change of bound bixin." Arch. Biochem. Biophys. 152 (1972): 36-43. 817B 23. Honychurch, P. N. 1980. Caribbean Wild Plants and Their Uses. Canada: 81B 24. Inada, Y. "Spectral changes of bixin upon interaction with respiring rat liver mitochondria." Arch. Biochem. Biophys. 146 (1971): 366-67. 819B 25. Kanjilal, P.B. and R.S. Singh. 1995. Agronomic evaluation of annatto (Bixa orellanaL.). Journal of Herbs, Spices, and Medicinal Plants 3(3): 13- 17. 820B 26. Katzer, G. 1999. Annatto (Bixa orellana L.). http://wwwang.kfunigraz.ac.at/~katzer/engl/Bixa_ore.html. 3 p. 821B 27. Lawrence BM, Hogg JW. Ishwarane in Bixa orellana leaf oil. Phytochemistry 1973;12: 2995. 82B 28. Liogier, H.A. 1990. Plantas medicinales de Puerto Rico y del Caribe. Iberoamericana de Ediciones, Inc., San Juan, PR. 563 p. 823B 29. Little, E.L., Jr., R.O. Woodbury, and F.H. Wadsworth. 1974. Trees of Puerto Rico and the Virgin Islands. Vol. 2. Agriculture Handbook 449. U.S. Department of Agriculture, Washington, DC. 1,024 p. 824B 30. Mabberley, D.J. 1987. The Plant Book. Cambridge, MA: 70. 825B 52 31. Magness, J.R., G.M. Markle, C.C. Compton. 1971. Food and feed crops of the United States. Interregional Research Project IR-4, IR Bul. 1 (Bul. 828 New Jersey Agr. Expt. Sta.). fide http://www.hort.purdue.edu/newcrop/Crops/achiote.html 32. Mercadante, A., A. Steck & H. Pfander. 1999. Three minor Carotenoids from annatto (Bixa orellana) seeds.Phytochemistry.52 (1): 135-139. 33. Mercadante, A.Z. & H. Pfander. 1998. Carotenoids from annatto: a review. Recent Research Developments in Agriculture and Food Chemistry 2(1): 79-91. 34. Morrison, E. Y., et al. "Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies." Trop. Georg. Med. 1991; 43(2): 184-88. 35. Morrison, E. Y., et al. "The effect of Bixa orellana (annatto) on blood sugar levels in the anaesthetized dog." West Indian Med. J. (March 1985). 36. Morrison, E. Y., et al. "Toxicity of the hyperglycaemic-inducing extract of the annatto (Bixa orellana) in the dog." West Indian Med. J. 1985; 34(1): 38-42. 37. Morton JF, 1981. Atlas of Medicinal Plants of Middle America. Bahamas to Yucatan. Ed. Charles C Thomas. Springfield. Illinois. 572-573. 38. Morton, J. & R. B. Ledin. 1952. 400 Plants of South Florida. Coral Gables, FL: 25. Morton, J. 1974. 500 Plants of South Florida. Miami, FL: 33. 39. Neal, M.C. 1965. In gardens of Hawaii. Special Publication 50. Bernice P. Bishop Museum Press, Honolulu, HI. 924 p. 40. Nepstad, D.C., C. Uhl, and E.A.S. Serrao. 1991. Recuperation of a degraded Amazonian landscape: forest recovery and agricultural restoration. Ambio 20(6): 248-255. 41. Nish, W. A., et al. "Anaphylaxis to annatto dye: a case report." Ann. Allergy 1991; 66(2): 129-31. 42. Otero R, Núñez V, Barona J, Fonnegra R, Jiménez SL, Osorio RG, Saldarriaga M, Díaz A. Snakebites and ethnobotany in the northwest region of Colombia; Part III: Neutralization of the haemorrhagic effect of Bothrops atrox venom. Journal of Ethnopharmacology 2000; 73; 233-241. 43. Parrotta, J.A. 2001. Healing plants of Peninsular India. CAB International, Wallingford, UK. 944 p. 44. Passos, M., L. Oliveira, A. Franca & G. Massarani.1998. Bixin powder production in conical bed units. Drying Technology.16 (9-10): 1855-1879. 45. Quisumbing, E. 1951. Medicinal Plants of the Philippines. Manila: 623-624. 46. Schultes, R. & R. Raffauf. 1990. The Healing Forest: Medicinal and Toxic Plants of the Northwest Amazonia. Portland, Oregon: 109-111. 47. Scita, G. "Retinoic acid and beta-carotene inhibit fibronectin synthesis aid release by fibroblasts; antagonism to phorbol ester." Carcinogenesis 15 (1994): 1043-48. 48. Smith, A. C. 1981. Flora Vitiensis nova: A new flora of Fiji. Lawai, Kauai, Hawaii. National Tropical Botanical Garden. 2:670. 53 49. Taylor, Leslie. Herbal Secrets of the Rainforest, 2nd edition. Sage Press, Inc., 2002 84B 50. Terashima S, Shimitzu M, Horie S, Morita N. Studies on aldose reductasa inhibitors from natural products. IV. Constituents and aldose reductase inhibitory efect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas. Chem. Pharm. Bull. 1991; 39: 3346-3347. 845B 51. Terashima, S., et al. "Studies on aldose reductase inhibitors from natural products, IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas." Chem. Pharm. Bull. 1991; 39(12): 3346-47. 846B 52. Tseng C, Iwakami S, Mikajiri A, Shibuya M, Hanaoka F, Ebizuka Y, Padmawinata K, Sankawa U. Inhibition of in vitro prostaglandin and leucotriene biosynteses by cinnamoyl-b-phenethylamine and nacyldopamine derivates. Chem. Pharm. Bull. 1992; 40:396-400. von Carlowitz, P.G. 1991. Multipurpose trees and shrubs, sources of seeds and inoculants. International Council for Research in Agroforestry, Nairobi, Kenya. 328 p. 847B 53. Wagner, W.L., D.R. Herbst and S.H. Sohmer. 1999. Manual of the flowering plants of Hawai'i. Revised edition. University of Hawai'i Press, Honolulu. p. 390. 84B 54. Warren, W. 1997. Tropical plants for home and garden. Thames and Hudson, New York. 240 p. 849B 55. Wheeler WM (1942) Studies on neo-tropical ant-plants and their ants. Bull. Mus. Comp. Zool. Harv. 90: 1-262. 850B 56. Williamson, J. 1955. Useful Plants of Nyasaland. Zomba, Nyasaland: 23. 851B 57. Wolf, M. A.1997. http://home.braunschweig.netsurf.de/~andree.wolf/urucum.html 852B 58. Zhang, L. X. "Carotenoids up-regulate connexin43 gene expression independent of their provitanin A or antioxidant properties." Cancer Res. 52 (1992): 5707-12. 853B References/Footnotes 1. Dunham, N. W. et al. "A preliminary pharmacologic investigation of the roots of Bixa orellana." J. Amer. Pharm. Ass. Sci. Ed. 1960; 49: 218. Morrison, E. Y., et al. "Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies." Trop. Georg. Med. 1991; 43(2): 184-88. Morrison, E. Y., et al. "Toxicity of the hyperglycaemic-inducing extract of the annatto (Bixa orellana) in the dog." West Indian Med. J. 1985; 34(1): 38-42. Morrison, E. Y., et al. "The effect of Bixa orellana (annatto) on blood sugar levels in the anaesthetized dog." West Indian Med. J. (March 1985). 854B 85B 2. Terashima, S., et al. "Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas." Chem. Pharm. Bull. 1991; 39(12): 3346-47. 856B 3. Otero, R., et al. "Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of lethal and enzymatic effects of Bothrops atrox venom." J. Ethnopharmacol. 2000; 71(3): 505-11. 857B 4. Cáceres A., et al. "Antigonorrhoeal activity of plants used in Guatemala for the treatment of sexually transmitted diseases." J. Ethnopharmacol. (October 1995). 85B 54 5. George, M., et al. "Investigations on plant antibiotics. Part IV. Further search for antibiotic substances in Indian medicinal plants." Indian J. Med. Res. 1949; 37: 169-81. 6. Bressani, R., et al. "Chemical composition, amino acid content and nutritive value of the protein of the annatto seed (Bixa orellana L.)." Arch. Latinoam. Nutr. 33(2): 356-76. \ 7. Scita, G. "Retinoic acid and beta-carotene inhibit fibronectin synthesis and release by fibroblasts; antagonism to phorbol ester." Carcinogenesis 15 (1994): 1043-48. 8. Zhang, L. X. "Carotenoids up-regulate connexin43 gene expression independent of their provitanin A or antioxidant properties." Cancer Res. 52 (1992): 5707-12. 9. Di Mascio, P. "Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers." Biochem. Soc. Trans. 18 (1990): 1054-6. 10. Hirose, S. "Energized state of mitochondria as revealed by the spectral change of bound bixin." Arch. Biochem. Biophys. 152 (1972): 36-43. 11. Inada, Y. "Spectral changes of bixin upon interaction with respiring rat liver mitochondria." Arch. Biochem. Biophys. 146 (1971): 366-67. 12. Campelo, C. R. "Contribuicao ao estudo das plantas medicinais no estado de alagoas III, VII." Simposio de Plantas Medicinais do Brasil, 1-3 de Setembro, 1982, Belo Horizonte-MG, 85m. 13. Nish, W. A., et al. "Anaphylaxis to annatto dye: a case report." Ann. Allergy 1991; 66(2): 129-31. MORE RESEARCH: 1. Cystitis, obesity, renal insufficiency, eliminate uric acid. Is very effective for Prostatitis and also for Vulgaris Acne Astringent, Nutritive, Emollient, Antibacterial, Antioxidant, Expectorant Antidysenteric for more information. 2. Terashima S, et al. Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas. Chem Pharm Bull (Tokyo), 1991 Dec 3. Morrison EY, et al. Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies. Trop Geogr Med, 1991 Jan-Apr 4. Nish WA, et al. Anaphylaxis to annatto dye: a case report. Ann Allergy, 1991 Feb 5. Morrison EY, et al. Toxicity of the hyperglycaemic-inducing extract of the annatto (Bixa orellana) in the dog. West Indian Med J, 1987 Jun 6. Morrison EY, et al. The effect of Bixa orellana (annatto) on blood sugar levels in the anaesthetized dog. West Indian Med J, 1985 Mar 7. Wurts ML, et al. [Analysis of the seed Bixa orellana, L. (annatto) and the waste generated in the extraction of its pigments] Arch Latinoam Nutr, 1983 Sep 8. Bressani R, et al. [Chemical composition, amino acid content and nutritive value of the protein of the annatto seed (Bixa orellana, L.)] Arch Latinoam Nutr, 1983 Jun 55 9. Ciscar F. Achiotin, an extract of achiote seeds (Bixa orellana L.), as a histologic stain for lipids. Stain Technol, 1965 Sep 87B Herbs Botanic's Dictionary Peru useful herbs by Antonio Brack Egg & PNUD & The Regional Andean Studies 07.07.01 ISBN 9972-691-21-0 1 "Physiological studies and Determination of Chromosome Number in Maca, Lepidium meyenii" by Carlos Quiros, A. Epperson, J. Hu, and M. Holle. Econ Bot 50 (2) 216-223, 1996. “According to folk belief, maca enhances female fertility in humans and domestic animals which tends to be reduced at higher altitudes. 2. Phytother Res. 2005 May;19(5):433-6. Pub Med PMID: 16106387 The effect of annatto on insulin binding properties in the dog. Russell KR, Morrison EY, Ragoobirsingh D. Source Department of Basic Medical Sciences, Biochemistry Section, University of the West Indies, Mona, Kingston 7, Jamaica. 87B 879B 80B 81B 82B 83B 84B MORE RESEARCH: 1. Cystitis, obesity, renal insufficiency, eliminate uric acid. Is very effective for Prostatitis and also for Vulgaris Acne Astringent, Nutritive, Emollient, Antibacterial, Antioxidant, Expectorant Antidysenteric for more information. 85B 86B 2. Terashima S, et al. Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas. Chem Pharm Bull (Tokyo), 1991 Dec 87B 3. Morrison EY, et al. Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies. Trop Geogr Med, 1991 Jan-Apr 8B 4. Nish WA, et al. Anaphylaxis to annatto dye: a case report. Ann Allergy, 1991 Feb 89B 5. Morrison EY, et al. Toxicity of the hyperglycaemic-inducing extract of the annatto (Bixa orellana) in the dog. West Indian Med J, 1987 Jun 890B 6. Morrison EY, et al. The effect of Bixa orellana (annatto) on blood sugar levels in the anaesthetized dog. West Indian Med J, 1985 Mar 891B 7. urts ML, et al. [Analysis of the seed Bixa orellana, L. (annatto) and the waste generated in the extraction of its pigments] Arch Latinoam Nutr, 1983 Sep 892B 8. Bressani R, et al. [Chemical composition, amino acid content and nutritive value of the protein of the annatto seed (Bixa orellana, L.)] Arch Latinoam Nutr, 1983 Jun 893B 9. Ciscar F. Achiotin, an extract of achiote seeds (Bixa orellana L.), as a histologic stain for lipids. Stain Technol, 1965 Sep 894B 10. Herbs Botanic's Dictionary Peru useful herbs by Antonio Brack Egg & PNUD & The Regional Andean Studies 07.07.01 ISBN 9972-691--21-0 895B 11. "Physiological studies and Determination of Chromosome Number in Maca, Lepidium meyenii" by Carlos Quiros, A. Epperson, J. Hu, and M. Holle. Econ Bot 50 (2) 216-223, 1996. “According to folk belief, maca enhances female fertility in humans and domestic animals which tends to be reduced at higher altitudes. 896B 56 Zinc Sulphate: 1. Sandstead HH. Understanding zinc: recent observations and interpretations. J Lab Clin Med 1994;124:322-7. [PubMed abstract] 2. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001. 3. Solomons NW. Mild human zinc deficiency produces an imbalance between cell-mediated and humoral immunity. Nutr Rev 1998;56:27-8. [PubMed abstract] 4. Prasad AS. Zinc: an overview. Nutrition 1995;11:93-9. [PubMed abstract] 5. Heyneman CA. Zinc deficiency and taste disorders. Ann Pharmacother 1996;30:186-7. [PubMed abstract] 6. Simmer K, Thompson RP. Zinc in the fetus and newborn. Acta Paediatr Scand Suppl 1985;319:158-63. [PubMed abstract] 7. Fabris N, Mocchegiani E. Zinc, human diseases and aging. Aging (Milano) 1995;7:77-93. [PubMed abstract] 8. Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 2006;20:3-18. [PubMed abstract] 9. Prasad AS, Beck FW, Grabowski SM, Kaplan J, Mathog RH. Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects. Proc Assoc Am Physicians 1997;109:68-77. [PubMed abstract] 10. Rink L, Gabriel P. Zinc and the immune system. Proc Nutr Soc 2000;59:541-52. [PubMed abstract] 11. U.S. Department of Agriculture, Agricultural Research Service. USDA Nutrient Database for Standard Reference, Release 14. [http://www.nal.usda.gov/fnic/foodcomp/search/] 12. Sandstrom B. Bioavailability of zinc. Eur J Clin Nutr 1997;51 (1 Suppl):S17-9. [PubMed abstract] 13. Wise A. Phytate and zinc bioavailability. Int J Food Sci Nutr 1995;46:53-63. [PubMed abstract] 14. Jafek BW, Linschoten MR, Murrow BW. Anosmia after intranasal zinc gluconate use. Am J Rhinol 2004;18:137-41. [PubMed abstract] 15. Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20. [PubMed abstract] 16. U.S. Food and Drug Administration. Warnings on Three Zicam Intranasal Zinc Products. [http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm166931.htm] 17. Alaimo K, McDowell MA, Briefel RR, Bischlf AM, Caughman CR, Loria CM, et al. Dietary Intake of Vitamins, Minerals, and Fiber of Persons Ages 2 Months and Over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988-91. Hyattsville, MD: Centers for Disease Control and Prevention, National Center for Health Statistics, 1994:1-28. 57 18. Interagency Board for Nutrition Monitoring and Related Research. Third Report on Nutrition Monitoring in the United States. Washington, DC: U.S. Government Printing Office, 1995. 915B 19. Ervin RB, Kennedy-Stephenson J. Mineral intakes of elderly adult supplement and non-supplement users in the third national health and nutrition examination survey. J Nutr 2002;132:3422-7. [PubMed abstract] 916B 20. Ribar DS, Hamrick KS. Dynamics of Poverty and Food Sufficiency. Food Assistance and Nutrition Report Number 36, 2003. Washington, DC: U.S. Department of Agriculture, Economic Research Service. [http://www.ers.usda.gov/publications/fanrr36/fanrr36.pdf] 917B 21. Dixon LB, Winkleby MA, Radimer KL. Dietary intakes and serum nutrients differ between adults from food-insufficient and food-sufficient families: Third National Health and Nutrition Examination Survey, 1988-1994. J Nutr 2001;131:1232-46. [PubMed abstract] 918B 22. Prasad AS. Zinc deficiency: its characterization and treatment. Met Ions Biol Syst 2004;41:103-37. [PubMed abstract] 91B 23. Wang LC, Busbey S. Images in clinical medicine. Acquired acrodermatitis enteropathica. N Engl J Med 2005;352:1121. [PubMed abstract] 920B 24. Hambidge KM, Mild zinc deficiency in human subjects. In: Mills CF, ed. Zinc in Human Biology. New York, NY: Springer-Verlag, 1989:281-96. 921B 25. King JC, Cousins RJ. Zinc. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins, RJ, eds. Modern Nutrition in Health and Disease, 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2005:271-85. 92B 26. Krasovec M, Frenk E. Acrodermatitis enteropathica secondary to Crohn's disease. Dermatology 1996;193:361-3. [PubMed abstract] 923B 27. Ploysangam A, Falciglia GA, Brehm BJ. Effect of marginal zinc deficiency on human growth and development. J Trop Pediatr 1997;43:192-8. [PubMed abstract] 924B 28. Nishi Y. Zinc and growth. J Am Coll Nutr 1996;15:340-4. [PubMed abstract] 925B 29. Hunt JR. Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am J Clin Nutr 2003;78 (3 Suppl):633S-9S. [PubMed abstract] 926B 30. Van Wouwe JP. Clinical and laboratory assessment of zinc deficiency in Dutch children. A review. Biol Trace Elem Res 1995;49:211-25. [PubMed abstract] 927B 31. Hambidge KM, Krebs NF. Zinc deficiency: a special challenge. J Nutr 2007;137:1101-5. [PubMed abstract] 928B 32. Prasad AS. Zinc deficiency in women, infants and children. J Am Coll Nutr 1996;15:113-20. [PubMed abstract] 92B 33. Naber TH, van den Hamer CJ, Baadenhuysen H, Jansen JB. The value of methods to determine zinc deficiency in patients with Crohn's disease. Scand J Gastroenterol 1998;33:514-23. [PubMed abstract] 930B 34. Valberg LS, Flanagan PR, Kertesz A, Bondy DC. Zinc absorption in inflammatory bowel disease. Dig Dis Sci. 1986 Jul;31(7):724-31. [PubMed abstract] 931B 58 35. Prasad AS. Zinc deficiency. BMJ 2003;326:409-10. [PubMed abstract] 36. American Dietetic Association, Dietitians of Canada. Position of the American Dietetic Association and Dietitians of Canada: vegetarian diets. J Am Diet Assoc 2003;103:748-65. [PubMed abstract] 37. Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr 1998;68 (2 Suppl):499S-508S. [PubMed abstract] 38. Krebs NF. Zinc supplementation during lactation. Am J Clin Nutr 1998;68 (2 Suppl):509S -12S. [PubMed abstract] 39. Brown KH, Allen LH, Peerson J. Zinc supplementation and children's growth: a meta-analysis of intervention trials. Bibl Nutr Dieta 1998;54:73-6. 40. Leonard MB, Zemel BS, Kawchak DA, Ohene-Frempong K, Stallings VA. Plasma zinc status, growth, and maturation in children with sickle cell disease. J Pediatr 1998;132:467-71. [PubMed abstract] 41. Zemel BS, Kawchak DA, Fung EB, Ohene-Frempong K, Stallings VA. Effect of zinc supplementation on growth and body composition in children with sickle cell disease. Am J Clin Nutr 2002;75:300-7. [PubMed abstract] 42. Prasad AS. Zinc deficiency in patients with sickle cell disease. Am J Clin Nutr 2002;75:181-2. [PubMed abstract] 43. Kang YJ, Zhou Z. Zinc prevention and treatment of alcoholic liver disease. Mol Aspects Med 2005;26:391-404. [PubMed abstract] 44. Menzano E, Carlen PL. Zinc deficiency and corticosteroids in the pathogenesis of alcoholic brain dysfunction—a review. Alcohol Clin Exp Res 1994;18:895-901. [PubMed abstract] 45. Navarro S, Valderrama R, To-Figueras J, Gimenez A, Lopez JM, Campo E, et al. Role of zinc in the process of pancreatic fibrosis in chronic alcoholic pancreatitis. Pancreas 1994;9:270-4. [PubMed abstract] 46. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 1998;68:447S-63S. [PubMed abstract] 47. Wintergerst ES, Maggini S, Hornig DH. Contribution of selected vitamins and trace elements to immune function. Ann Nutr Metab 2007;51:301-23. [PubMed abstract] 48. Beck FW, Prasad AS, Kaplan J, Fitzgerald JT, Brewer GJ. Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. Am J Physiol 1997;272:E1002-7. [PubMed abstract] 49. Prasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 2000;182 (Suppl):S62-8. [PubMed abstract] 50. Bahl R, Bhandari N, Hambidge KM, Bhan MK. Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting. Am J Clin Nutr 1998;68 (2 Suppl):414S-7S. [PubMed abstract] 59 51. Brooks WA, Santosham M, Naheed A, Goswami D, Wahed MA, Diener-West M, et al. Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial. Lancet 2005;366:999-1004. [PubMed abstract] 948B 52. Meydani SN, Barnett JB, Dallal GE, Fine BC, Jacques PF, Leka LS, et al. Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr 2007;86:1167-73. [PubMed abstract] 94B 53. Black RE. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr 2003;133:1485S-9S. [PubMed abstract] 950B 54. Lansdown AB, Mirastschijski U, Stubbs N, Scanlon E, Agren MS. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen 2007;15:2-16. [PubMed abstract] 951B 55. Anderson I. Zinc as an aid to healing. Nurs Times 1995;91:68, 70. [PubMed abstract] 952B 56. Wilkinson EA, Hawke CI. Does oral zinc aid the healing of chronic leg ulcers? A systematic literature review. Arch Dermatol 1998;134:1556-60. [PubMed abstract] 953B 57. Wilkinson EA, Hawke CI. Oral zinc for arterial and venous leg ulcers. Cochrane Database Syst Rev 2000;(2):CD001273. [PubMed abstract] 954B 58. World Health Organization and United Nations Children Fund. Clinical management of acute diarrhoea. WHO/UNICEF Joint Statement, August, 2004. [ http://www.unicef.org/nutrition/files/ENAcute_Diarrhoea_reprint.pdf] 95B 59. Black RE. Therapeutic and preventive effects of zinc on serious childhood infectious diseases in developing countries. Am J Clin Nutr 1998;68:476S-9S. [PubMed abstract] 956B 60. Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000;72:1516-22. [PubMed abstract] 957B 61. Lukacik M, Thomas RL, Aranda JV. A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics 2008;121:326-36. [PubMed abstract] 958B 62. Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis 2007;45 (1 Suppl):S73-7. [PubMed abstract] 95B 63. Hulisz D. Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc (2003) 2004;44:594-603. [PubMed abstract] 960B 64. Caruso TJ, Prober CG, Gwaltney JM Jr. Treatment of naturally acquired common colds with zinc: a structured review. Clin Infect Dis 2007;45:569-74. [PubMed abstract] 961B 65. Prasad AS, Beck FW, Bao B, Snell D, Fitzgerald JT. Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate. J Infect Dis 2008 ;197:795-802. [PubMed abstract] 962B 66. Turner RB, Cetnarowski WE. Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 2000;31:1202-8. [PubMed abstract] 963B 60 67. Eby GA, Halcomb WW. Ineffectiveness of zinc gluconate nasal spray and zinc orotate lozenges in common-cold treatment: a double-blind, placebo-controlled clinical trial. Altern Ther Health Med 2006;12:34-8. [PubMed abstract] 68. Marshall I. Zinc for the common cold. Cochrane Database Syst Rev 2000;(2):CD001364. [PubMed abstract] 69. Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 2006;(2):CD000254. [PubMed abstract] 70. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119:1417-36. [PubMed abstract] 71. van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 2005;294:3101-7. [PubMed abstract] 72. Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH. Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis. BMJ 2007;335:755. [PubMed abstract] 73. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E. Oral zinc in macular degeneration. Arch Ophthalmol 1988;106:192-8. [PubMed abstract] 74. Stur M, Tittl M, Reitner A, Meisinger V. Oral zinc and the second eye in age-related macular degeneration. Invest Ophthalmol Vis Sci 1996;37:1225-35. [PubMed abstract] 75. Whittaker P. Iron and zinc interactions in humans. Am J Clin Nutr 1998;68:442S-6S. [PubMed abstract] 76. Broun ER, Greist A, Tricot G, Hoffman R. Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression. JAMA 1990;264:1441-3. [PubMed abstract] 77. Willis MS, Monaghan SA, Miller ML, McKenna RW, Perkins WD, Levinson BS, et al. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol 2005;123:125-31. [PubMed abstract] 78. Lewis MR, Kokan L. Zinc gluconate: acute ingestion. J Toxicol Clin Toxicol 1998;36:99-101. [PubMed abstract] 79. Hooper PL, Visconti L, Garry PJ, Johnson GE. Zinc lowers high-density lipoprotein-cholesterol levels. J Am Med Assoc 1980;244:1960-1. [PubMed abstract] 80. Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol 2007;177:639-43. [PubMed abstract] 81. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. [PubMed abstract] 82. Penttilä O, Hurme H, Neuvonen PJ. Effect of zinc sulphate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4. [PubMed abstract] 61 83. Natural Medicines Comprehensive Database. Zinc. [http://www.NaturalDatabase.com] 980B 84. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, Dick RD, Wang Y. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. [PubMed abstract] 981B 85. Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. [PubMed abstract] 982B Acne Treatment Zinc sulfate is believed to help heal blemishes caused by acne, according to Healthy-Skincare.com, as well as reduce inflammation. Further research is still needed, however, to establish a correlation between the amount of zinc in the body and its effects on treating acne breakouts. Dissolve Artery Blockages Increase Blood Flow Dramatically Safely Restore Cardio Health www.arteryhealth.co.uk Sponsored Links 983B 984B 985B 986B Diarrhea Treatment Ongoing studies have shown that zinc sulfate may relieve the duration and severity of diarrhea, according to research from the FDA. It appears particularly effective when used by malnourished children, who typically suffer from zinc deficiency. 987B 98B Immune System Health & Wound Healing Zinc sulfate supplementation may help promote a healthy immune system, according to Vitamins-Nutrition.org. Zinc is vital in the production of T-cells, which help fight infections. A strong immune system supported through healthy zinc levels ensure that infections and open wounds heal quickly. 98B 90B Sickle Cell Anemia Treatment Symptoms of sickle cell anemia may be managed better through zinc sulfate supplementation, due to the zinc deficiency many sickle cell patients suffer, according to The American Journal of Clinical Research. Studies indicate that patients with low levels of zinc suffered from several symptoms, including a cell-mediated immune disorder, a characteristic of sickle cell disease. 91B 92B Zinc Deficiency Treatment Read more: http://www.livestrong.com/article/253219-the-benefits-of-zinc-sulfate/#ixzz1FydeZzMv Delineation of the protective action of zinc sulfate on ulcerative colitis in rats. Luk HH, Ko JK, Fung HS, Cho CH. Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 1/F, Li Shu Fan Building, 5 Sassoon Road, Hong Kong, PR China. 93B 94B 95B 96B 97B The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats. Zinc sulfate at different concentrations was given either orally (p.o.) or rectally (p.r.) to rats at 42, 48, 66 and 72 h following the induction of colonic inflammation by DNBS. Rats were killed 96 h after instillation of DNBS rectally to assess the severity of colonic damage, myeloperoxidase and xanthine oxidase activities. The involvement of mast cell degranulation and histamine release in the pathogenesis of DNBS-induced colitis was determined by using a mast cell stabilizer (ketotifen) and histamine receptor blockers (terfenadine and ranitidine). DNBS given rectally produced inflammation and ulceration in rats with a pathology resembling ulcerative colitis. Myeloperoxidase activity but not xanthine oxidase activity was sharply increased by this agent. Intrarectal administration of zinc solution and parenteral injection of histamine blockers significantly reduced tissue damage and myeloperoxidase but not xanthine 98B 62 oxidase activity. Ketotifen, a mast cell stabilizer, also significantly decreased mucosal injury and myeloperoxidase activity in the colon. In conclusion, mast cell degranulation followed by histamine release plays an important role in the pathogenesis of DNBS-induced ulcerative colitis. Zinc given rectally has a therapeutic effect against this colitis model, perhaps through the reduction of inflammation and inhibition of the above pathogenic mechanisms. PMID: 12044810 [PubMed - indexed for MEDLINE] Clinical double-blind trial of topical zinc sulfate for herpes labialis recidivans]. Kneist W, Hempel B, Borelli S. Klinik für Dermatologie und Allergie Davos, Alexanderhausklinik, Davos Platz, Schweiz. Abstract In a placebo controlled, double-blind clinical trial in patients with herpes labialis recidivans, zinc sulfate (CAS 7733-02-0) as gel (Virudermin Gel) proved to be significantly more effective than the gel alone. With zinc sulfate as gel, the symptoms were less marked and healing was faster. This simple preparation can be applied in cases of herpes labialis recidivans without any risk of side effects. Due to the antiseptic properties of zinc sulfate superinfections can be prevented. Canine zinc-responsive dermatosis. Colombini S. Veterinary Teaching Hospital and Clinics, School of Veterinary Medicine, Louisiana State University, Baton Rouge, USA. Zinc-responsive Dermatosis in Dogs. www.gopetsamerica.com/dog-health/zinc_responsive_dermatosis.aspx http://www.nutro.com/nutrition-philosophy/natural-cat-dog-food-ingredients.aspx#divT-ZSection Memorial Sloan-Ketting Medical Center Marchisio P, Esposito S, Bianchini S, et al. Effectiveness of a propolis and zinc solution in preventing acute otitis media in children with a history of recurrent acute otitis media. Int J Immunopathol Pharmacol. 2010 AprJun;23(2):567-75. This randomized, single-blinded, prospective study enrolled 122 children (aged 1-5 years) with a history of recurrent acute otitis media (AOM). Respiratory-related morbidity and AOM were assessed at baseline and every 4 weeks. Environmental risk factors (smoke, pacifier use, full-time day care attendance) were eliminated for both the treatment and placebo groups. During the 3 month treatment period, AOM was diagnosed in 50.8% (n=31) of the patients receiving the propolis/zinc suspension (n=61), and 70.5% (n=43) of the children in the control group (n=61;p=0.04). The mean number of AOM episodes per child/per month was 0.23 + 0.26 for the propolis/zinc treatment group and 0.34 + 0.29 for the control group (p=0.03). No effect on any other types of respiratory infections was detected. Investigators concluded that the propolis/zinc suspension safely and significantly reduced the risk of new AOM episodes in children with a history of recurrent AOM. For Cat’s Claw Extract: Immunostimulant & Immunomodulatory Actions: 1. Spelman, K., et al. "Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators." Altern. Med. Rev. 2006 Jun; 11(2): 128-50. 2. Eberlin, S., et al. “Uncaria tomentosa extract increases the number of myeloid progenitor cells in the bone marrow of mice infected with Listeria monocytogenes.” Int. Immunopharmacol. 2005; 5(78):1235-46. 3. Deharo, E., et al. ”In vitro immunomodulatory activity of plants used by the Tacana ethnic group in Bolivia.” Phytomedicine. 2004 Sep; 11(6): 516-22. 4. Lamm, S., et al, “Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100." Phytomedicine. 2001; 8(4): 267–74. 63 5. Sheng Y, et al., “Treatment of chemotherapy-induced leucopenia in a rat model with aqueous extract from Uncaria tomentosa.” Phytomedicine. 2000; 7(2): 137–43. 106B 6. Lemaire, I., et al. “Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (una de gato).” J. Ethnopharmacol. 1999; 64(2): 109–15. 107B 7. Marina, M. D. “Evaluacion de la actividal immunoestimulante de Uncaria tomentosa (Willd.) DC. Una de gato en ratones albinos." Biodiversidad Salud. 1998; 1(1): 16–19. 108B 8. Keplinger, H., et al. “Oxindole alkaloids having properties stimulating the immunologic system and preparation containing same.” United States patent 5,302,611; April 12, 1994 109B 9. Wagner, H., et al. “Die Alkaloide von Uncaria tomentosa und ihre Phagozytose-steigernde Wirkung." Planta Med. 1985; 51: 419–23. 102B 10. Hemingway, S. R. and J. D. Phillipson. “Alkaloids from South American species of Uncaria (Rubiaceae)." J. Pharm. Pharmacol. 1974 suppl.; 26: 113p. 102B Anti-inflammatory Actions: 1. Hardin, S. R. "Cat's claw: An Amazonian vine decreases inflammation in osteoarthritis." Complement. Ther. Clin. Pract. 2007 Feb; 13(1): 25-8. 102B 1023B 2. Allen-Hall, L., et al. "Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates the expression if IL-1beta and TNF-alpha." J. Ethnopharmacol. 2007 Jan; 109(2): 312-7. 1024B 3. Miller, M. J., et al. "The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta." BMC Complement. Altern. Med. 2006 Apr; 6: 13. 1025B 4. Miller, M. J., et al. "Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711]." J. Inflamm. 2005 Oct; 2:11. 1026B 5. Valerio, L. G., et al. "Toxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii): a critical synopsis." Toxicol. Rev. 2005; 24(1): 11-35. 1027B 6. Setty, A. R., et al. "Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects." Semin. Arthritis Rheum. 2005; 34(6): 773-84. 1028B 7. Sheng, Y., et al. “An active ingredient of Cat's Claw water extracts: identification and efficacy of quinic acid.” J. Ethnopharmacol. 2005 Jan 15; 96(3): 1029B 8. Aguilar, J. L., et al. “Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae).” J. Ethnopharmacol. 2002; 81(2): 271–76. 103B 9. Sandoval, M., et al., “Anti-inflammatory and antioxidant activities of cat’s claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content." Phytomedicine. 2002; 9(4): 325–37. 103B 10. Mur, E., et al. “Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis.” J. Rheumatol. 2002 Apr; 29(4): 678–81. 1032B 11. Sandoval-Chacon, M., et al. “Anti-inflammatory actions of cat’s claw: the role of NF-kappaB.” Aliment. Pharmacol. Ther. 1998; 12(12): 1279–89. 103B 64 12. Recio, M. C., et al. “Structural requirements for the anti-inflammatory activity of natural triterpenoids.” Planta Med. 1995; 61(2): 182–85. 13. Aquino, R., et al. “Plant metabolites. New compounds and anti-inflammatory activity of Uncaria tomentosa." J. Nat. Prod. 1991; 54: 453–59. 14. Cerri, R., et al. “New quinovic acid glycosides from Uncaria tomentosa." J. Nat. Prod. 1988; 51: 257– 61. Anticancerous & Antitumor Actions: 1. Gonzales, G.F., et al. "Medicinal plants from Peru: a review of plants as potential agents against cancer." Anticancer Agents Med. Chem. 2006 Sep; 6(5): 429-44. 2. De Martino, L., et al. "Proapoptotic effect of Uncaria tomentosa extracts." J. Ethnopharmacol. 2006 Aug; 107(1): 91-4. 3. Bacher, N., et al. "Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1arrested and bcl-2-expressing acute lymphoblastic leukaemia cells." Br. J. Haematol. 2006 Mar; 132(5): 615-22. 4. Riva, L., et al. “The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line." Anticancer Res. 2001; 21(4A): 2457–61. 5. Muhammad, I., et al. “Investigation of Una de Gato I. 7-Deoxyloganic acid and 15N NMR spectroscopic studies on pentacyclic oxindole alkaloids from Uncaria tomentosa." Phytochemistry. 2001; 57(5): 781– 5. 6. Sheng, Y., et al. “Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa." Anticancer Res. 1998; 18(5A): 3363–68. 7. Salazar, E. L., et al. “Depletion of specific binding sites for estrogen receptor by Uncaria tomentosa." Proc. West. Pharmacol. Soc. 1998; 41(1): 123–124. 8. Stuppner, H., et al. “A differential sensitivity of oxindole alkaloids to normal and leukemic cell lines.” Planta Med. (1993 suppl.); 59: A583. 9. Rizzi, R., et al. “Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts." J. Ethnopharmacol. 1993; 38: 63–77. 10. Peluso, G., et al. “Effetto antiproliferativo su cellule tumorali di estrattie metaboliti da Uncaria tomentosa. Studi in vitro sulla loro azione DNA polimerasi.” 11 Congreso Italo-Peruano de Etnomedicina Andina, Lima, Peru, October 27–30, 1993, 21–2. 11. Rizzi, R., et al. “Bacterial cytotoxicity, mutagenicity and antimutagenicity of Uncaria tomentosa and its extracts. Antimutagenic activity of Uncaria tomentosa in humans." Premiere Colloque Européan d'Ethnopharmacologie, Metz, France, March 22–24, 1990. Cellular Protective & Antioxidant Actions: 1. Mammone, T., et al. "A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin." Phytother. Res. 2006; 20(3): 178-83. 65 2. Kuras, M., et al. "Changes in chromosome structure, mitotic activity and nuclear DNA content from cells of Allium Test induced by bark water extract of Uncaria tomentosa (Willd.) DC." J. Ethnopharmacol. 2006 Sep; 107(2): 211-21. 105B 3. Pilarski, R., et al. "Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC." J. Ethnopharmacol. 2006 Mar; 104(1-2): 18-23. 1052B 4. Cisneros, F. J., et al. “An Uncaria tomentosa (cat's claw) extract protects mice against ozone-induced lung inflammation.” J. Ethnopharmacol. 2005 Jan; 96(3): 355-64. 1053B 5. Goncalves, C., et al. “Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity.” Phytochemistry. 2005; 66(1): 89-98. 1054B 6. Romero-Jimenez, M., et al. “Genotoxicity and anti-genotoxicity of some traditional medicinal herbs.” Mutat. Res. 2005 Aug; 585(1-2): 147-55. 105B 7. Pilarski, R., et al. “Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC.” J. Ethnopharmacol. 2005 Sep 29; 1056B 8. Sheng, Y., et al. “DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study." Phytomedicine. 2001; 8(4): 275–82. 1057B 9. Sheng, Y., et al. “Enhanced DNA repair, immune function and reduced toxicity of C-Med-100, a novel aqueous extract from Uncaria tomentosa." J. Ethnopharmacol. 2000; 69(2): 115–26. 1058B 10. Sandoval, M., et al. “Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection.” Free Radic. Biol. Med. 2000; 29(1): 71–8. 1059B 11. Desmarchelier, C., et al. “Evaluation of the in vitro antioxidant activity in extracts of Uncaria tomentosa (Willd.) DC." Phytother. Res. 1997; 11(3): 254–256. 106B 12. Chan-Xun, C., et al. “Inhibitory effect of rhynchophylline on platelet aggregation and thrombosis.” Acta Pharmacologica Sinica 1992; 13(2): 126–30. 106B Actions on the Brain and Memory: 1. Jurgensen, S., et al. “Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa.” Pharmacol. Biochem. Behav. 2005 Jul; 81(3): 466-77. 1062B 1063B 2. Kang, T. H., et al. “Pteropodine and isopteropodine positively modulate the function of rat muscarinic M(1) and 5-HT(2) receptors expressed in Xenopus oocyte.” Eur. J. Pharmacol. 2002 May; 444(1-2): 3945. 1064B 3. Mohamed, A. F., et al. “ Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.” J. Pharm. Pharmacol. 2001; 52(12): 1553–61. 1065B 4. Roth, B. L., et al. “Insights into the structure and function of 5-HT(2) family serotonin receptors reveal novel strategies for therapeutic target development.” Expert Opin. Ther. Targets 2001 Dec; 5(6): 685695. 106B 5. Castillo, G. "Methods of isolation of amyloid inhibitory ingredients within Uncaria tomentosa." US Patent No 7,029,710, April, 18, 2006. 1067B 66 6. Castillo, G. " Methods of isolating amyloid-inhibiting compounds and use of compounds isolated from Uncaria tomentosa and related plants." US Patent No. 6,929,808, August 16, 2005. 7. Castillo, G., et al. “Pharmaceutical compositions containing Uncaria tomentosa extract for treating Alzheimer's disease and other amyloidoses." Patent-Pct. Int. Paol. 1998; 00 33,659: 67pp. Antimicrobial Actions: 1. Kloucek, P., et al. “Antibacterial screening of some Peruvian medicinal plants used in Calleria District.” J. Ethnopharmacol. 2005 Jun; 99(2): 309-12. 2. Garcia, R., et al. “Antimicrobial activity of isopteropodine.” Z. Naturforsch. 2005; 60(5-6): 385-8. 3. Aquino, R., et al. “Plant metabolites. Structure and in vitro antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda." J. Nat. Prod. 1989; 4(52): 679–85. 4. The Mayo Clinic is presently studying Cat’s Claw to determine if it will help reduce hypertension. 5. The Mayo Clinic a Guide for Alternative Medicine. The Time Inc Editor Brent Baur , M.D MEMORIAL SLOAN KETTERING RESEARCH Scientific Name Uncaria tomentosa Common Name Una de gato, life-giving vine of Peru, hawk's claw Clinical Summary Cat's claw is a vine native to South America. The bark of this plant has been used in traditional medicine to treat diseases. It is also a very popular immune-enhancing supplement. In vitro studies show that the alkaloids from Cat's claw enhance phagocytosis, display immunomodulatory properties, alleviate inflammation, and possess anti-viral activity. Cat's claw is also thought to have anticancer activities and lab results demonstrated growth inhibitory effects on glioma and neuroblastoma cells as well as promyelocytic leukemia cells. However, no human studies have been conducted to evaluate efficacy. Reported adverse reactions include hypotension and diarrhea. An additive effect with anticoagulants or hypotensives is possible; therefore caution should be exercised. Purported uses Cancer treatment GI disorders HIV and AIDS Inflammation Constituents • Oxindole alkaloids: Isopteropodine, pteropodine, rhynchophylline, mytraphylline, speciphylline • Indole alkaloidal glucosides: Cadambine, 3-dihydrocadambine, and 3-isodihydrocadambine • Hirsutine • Quinovic acid glycosides • Tannins • Polyphenols • Catechins • Beta sitosterol 67 Mechanism of Action The oxindole alkaloids are claimed to have immunostimulating properties in vitro, increasing phagocytotic activity and synthesis of WBCs and enhancing T-helper cell function. The major alkaloid, rhynchophylline, is claimed to be anti-hypertensive; it relaxes the endothelial cells of blood vessels, dilates peripheral blood vessels, inhibits sympathetic nervous system activities, and lowers the heart rate and blood cholesterol. The alkaloid mytraphylline has diuretic properties, and hirsutine inhibits urinary bladder contractions and possesses local anesthetic. The anti-inflammatory activity may be caused by the inhibition of TNF-alpha production. Uncaria tomentosa water extracts have been shown to enhance DNA repair after chemical-induced damage. 1097B 1098B Literature Summary and Critique Animal and in vitro data exist in cancer, immunostimulant, inflammation, and antiviral studies. Human studies are lacking, and further research is needed. 109B 10B References 1. Riva L, et al. The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line. Anticancer Res 2001;21:2457-61. 10B 102B 2. Sandoval M, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-8. 103B 3. Sandoval M, et al. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine 2002;9:325-37. 104B 4. Sheng Y, Bryngelsson C, Pero R. Enhanced DNA repair, immune function and reduced toxicity of CMED-100, a novel aqueous extract from Uncaria tomentosa. J Ethnopharmacol 2000;69:115-26. 105B 5. Reis SR, Valente LM, Sampaio AL, et al. Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2. Int Immunopharmacol. Mar 2008;8(3):468-476. 106B 6. Garcia Prado E, Garcia Gimenez MD, De la Puerta Vazquez R, Espartero Sanchez JL, Saenz Rodriguez MT. Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines. Phytomedicine. Apr 2007;14(4):280-284. 107B 7. Pilarski R, Poczekaj-Kostrzewska M, Ciesiolka D, Szyfter K, Gulewicz K. Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells. Pharmacol Rep. SepOct 2007;59(5):565-572. 108B 8. Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health-Syst Pharm 2002;59:339-47. 109B 9. Hemingway SR, Phillipson JD. Proceedings: alkaloids from south American species of Uncaria (Rubiaceae). J Pharm Pharmacol 1974;26(suppl):113. 10B 10. Wirth C, et al. Pharmacologically active procyanidines from the bark of Uncaria tomentose. Phytomedicine 1997;4:265-6. 1B 11. Aquino R, et al. Plant metabolites: New compounds and anti-inflammatory activity of Uncaria tomentosa. J Nat Prod 1991;54:453-9. 12B 12. Rizzi R, et al. Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. J Ethnopharmacol 1993;38:63-77. 13B 68 13. Sheng Y, et al. DNA repair of aqueous extracts of Uncaria tomentosa in a human volunteer study. Phytomedicine 2001;8:275-82. 14. Hilepo JN, et al. Acute renal failure caused by 'cat's claw' herbal remedy in a patient with systemic lupus erythematosus. Nephron 1997;77:361. OTHER RESEARCH: Cat's claw. Natural Medicines Comprehensive Database Web site. Accessed on July 5, 2007. Cat's claw (Uncaria tomentosa, Uncaria guianensis). Natural Standard Database Web site. Accessed on July 3, 2007. “Uncaria tomentosa, also known as cat’s claw, an herb from the highlands of the Peruvian Amazon, has been used by natives for hundreds of years to treat immunologic and digestive disorders. Research began in the 1970s to discover the benefits of this plant in relieving symptoms of cancers, arthritis, and other ailments. It has the ability to cleanse the digestive tract, aiding victims of Crohn’s, colitis, gastritis and more. In a 1989 study by Klaus Keplinger, several alkaloid oxidants found in the plant’s roots showed an ability to stimulate the immune system. The principal alkaloids are isopteropodine and rynchophyiline. Extracts of cat’s claw mixed with AZT in an experimental drug, called Krallendom, were effective in reducing symptoms in AIDS patients in Austria. The plant has been useful in reducing secondary effects of radiation and chemotherapy in cancer victims as well.” Steinberg PN Sidahora. 1995 Apr-May;:35-6. 1. An extract of Uncaria tomentosa inhibiting cell division and NF-kappa B activity without inducing cell death. Akesson C, Lindgren H, Pero RW, Leanderson T, Ivars F. Section for Immunology, Department of Cell and Molecular Biology, BMC I:13, Lund University, Lund, SE-221 84, Sweden. Int Immunopharmacol. 2003 Dec;3(13-14):1889-900. PMID: 14636838 [PubMed - in process] 2. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Sheng Y, Pero RW, Amiri A, Bryngelsson C. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Anticancer Res. 1998 Sep-Oct;18(5A):3363-8 PMID: 9858909 [PubMed - indexed for MEDLINE] 3. Antiinflammatory actions of cat’s claw: the role of NF-kappaB. Sandoval-Chacon M, Thompson JH, Zhang XJ, Liu X, Mannick EE, Sadowska-Krowicka H, Charbonnet RM, Clark DA, Miller MJ. LSU Medical Center, Department of Paediatrics and Stanley S. Scott Cancer Center, New Orleans, LA 70112, USA. Aliment Pharmacol Ther. 1998 Dec;12(12):1279-89. PMID: 9882039 [PubMed - indexed for MEDLINE] 4. Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ. Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. [email protected] Free Radic Biol Med. 2000 Jul 1;29(1):71-8 PMID: 10962207 [PubMed - indexed for MEDLINE] 69 5. Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis. Miller MJ, Angeles FM, Reuter BK, Bobrowski P, Sandoval M. Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. [email protected] BMC Complement Altern Med. 2001;1(1):11. Epub 2001 Dec 10 PMID: 11749672 [PubMed - indexed for MEDLINE] 14B 142B 143B 14B 145B 6. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Sheng Y, Li L, Holmgren K, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2001 Jul;8(4):275-82 PMID: 11515717 [PubMed - indexed for MEDLINE] 146B 147B 148B 149B 150B 7. Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test. Mohamed AF, Matsumoto K, Tabata K, Takayama H, Kitajima M, Watanabe H. Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan. PMID: 11197086 [PubMed - indexed for MEDLINE] 15B 152B 153B 154B 8. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa. Sheng Y, Bryngelsson C, Pero RW. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] J Ethnopharmacol. 2000 Feb;69(2):115-26. PMID: 10687868 [PubMed - indexed for MEDLINE] 15B 156B 157B 158B 159B 9. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa. Sheng Y, Pero RW, Wagner H. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2000 Apr;7(2):137-43. PMID: 10839217 [PubMed - indexed for MEDLINE] 160B 16B 162B 163B 164B 10. Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100. Lamm S, Sheng Y, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. Phytomedicine. 2001 Jul;8(4):267-74 PMID: 11515716 [PubMed - indexed for MEDLINE] 165B 16B 167B 168B 169B 11. In vitro Effects of Two Extracts and Two Pure Alkaloid Preparations of Uncaria tomentosa on Peripheral Blood Mononuclear Cells. Winkler C, Wirleitner B, Schroecksnadel K, Schennach H, Mur E, Fuchs D. Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria. Planta Med. 2004 Mar;70(3):205-10. PMID: 15114496 [PubMed - in process] 170B 17B 172B 173B 174B 12. An extract of Uncaria tomentosa inhibiting cell division and NF-kappa B activity without inducing cell death. 175B 70 Akesson C, Lindgren H, Pero RW, Leanderson T, Ivars F. Section for Immunology, Department of Cell and Molecular Biology, BMC I:13, Lund University, Lund, SE-221 84, Sweden. Int Immunopharmacol. 2003 Dec;3(13-14):1889-900. Previous reports have demonstrated that extracts of the plant Uncaria tomentosa inhibit tumor cell proliferation and inflammatory responses. We have confirmed that C-Med 100, a hot water extract of this plant, inhibits tumor cell proliferation albeit with variable efficiency. We extend these findings by showing that this extract also inhibits proliferation of normal mouse T and B lymphocytes and that the inhibition is not caused by toxicity or by induction of apoptosis. Further, the extract did not interfere with IL-2 production nor IL-2 receptor signaling. Since there was no discrete cell cycle block in C-Med 100-treated cells, we propose that retarded cell cycle progression caused the inhibition of proliferation. Collectively, these data suggested interference with a common pathway controlling cell growth and cell cycle progression. Indeed, we provide direct evidence that C-Med 100 inhibits nuclear factor kappa B (NF-kappa B) activity and propose that this at least partially causes the inhibition of proliferation. PMID: 14636838 [PubMed - in process] 13. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Sheng Y, Pero RW, Amiri A, Bryngelsson C. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Anticancer Res. 1998 Sep-Oct;18(5A):3363-8 Growth inhibitory activities of novel water extracts of Uncaria tomentosa (C-Med-100) were examined in vitro using two human leukemic cell lines (K562 and HL60) and one human EBV-transformed B lymphoma cell line (Raji). The proliferative capacities of HL60 and Raji cells were strongly suppressed in the presence of the C-Med-100 while K562 was more resistant to the inhibition. Furthermore, the antiproliferative effect was confirmed using the clonogenic assay, which showed a very close correlation between C-Med-100 concentration and the surviving fraction. The suppressive effect of Uncaria tomentosa extracts on tumor cell growth appears to be mediated through induction of apoptosis which was demonstrated by characteristic morphological changes, internucleosomal DNA fragmentation after agarose gel electrophoresis and DNA fragmentation quantification. C-Med-100 induced a delayed type of apoptosis becoming most dose-dependently prominent after 48 hours of exposure. Both DNA single and double strand breaks were increased 24 hours after C-Med-100 treatment, which suggested a wellestablished linkage between the DNA damage and apoptosis. The induction of DNA strand breaks coupled to apoptosis may explain the growth inhibition of the tumor cells by Uncaria tomentosa extracts. These results provide the first direct evidence for the antitumor properties of Uncaria tomentosa extracts to be via a mechanism of selective induction of apoptosis. PMID: 9858909 [PubMed - indexed for MEDLINE] 14. Antiinflammatory actions of cat’s claw: the role of NF-kappaB. Sandoval-Chacon M, Thompson JH, Zhang XJ, Liu X, Mannick EE, Sadowska-Krowicka H, Charbonnet RM, Clark DA, Miller MJ. LSU Medical Center, Department of Paediatrics and Stanley S. Scott Cancer Center, New Orleans, LA 70112, USA. Aliment Pharmacol Ther. 1998 Dec;12(12):1279-89. BACKGROUND: Uncaria tomentosa is a vine commonly known as cat’s claw or ‘una de gato’ (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. PURPOSE: The aim of this study was to determine the proposed anti-inflammatory properties of cat’s claw. Specifically: (i) does a bark extract of cat’s claw protect against oxidant-induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. METHODS: Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 microM). Gene expression of inducible nitric oxide synthase (iNOS) 71 in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF-kappaB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). RESULTS: The administration of UG (100 microg/mL) attenuated (P < 0.05) peroxynitrite-induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat’s claw inhibited lipopolysaccharide-induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF-kappaB. Cat’s claw markedly attenuated indomethacin-enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. CONCLUSIONS: Cat’s claw protects cells against oxidative stress and negated the activation of NFkappaB. These studies provide a mechanistic evidence for the widely held belief that cat’s claw is an effective anti-inflammatory agent. PMID: 9882039 [PubMed - indexed for MEDLINE] 192B 15. Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ. Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. [email protected] Free Radic Biol Med. 2000 Jul 1;29(1):71-8 Cat’s claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat’s claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat’s claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 microg/ml, p <.05). Cat’s claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat’s claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat’s claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha production. The primary mechanism for cat’s claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis. PMID: 10962207 [PubMed - indexed for MEDLINE] 193B 194B 195B 196B 197B 198B 16. Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis. Miller MJ, Angeles FM, Reuter BK, Bobrowski P, Sandoval M. Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. [email protected] BMC Complement Altern Med. 2001;1(1):11. Epub 2001 Dec 10 BACKGROUND: The potential of ascorbic acid and two botanical decoctions, green tea and cat’s claw, to limit cell death in response to oxidants were evaluated in vitro. METHODS: Cultured human gastric epithelial cells (AGS) or murine small intestinal epithelial cells (IEC-18) were exposed to oxidants DPPH (3 microM), H2O2 (50 microM), peroxynitrite (300 microM) - followed by incubation for 24 hours, with antioxidants (10 microg/ml) administered as a 1 hour pretreatment. Cell number (MTT assay) and death via apoptosis or necrosis (ELISA, LDH release) was determined. The direct interactions between antioxidants and DPPH (100 microM) or H2O2 (50 microM) were evaluated by spectroscopy. RESULTS: The decoctions did not interact with H2O2, but quenched DPPH although less effectively than vitamin C. In contrast, vitamin C was significantly less effective in protecting human gastric epithelial cells (AGS) from apoptosis induced by DPPH, peroxynitrite and H2O2 (P < 0.001). Green tea and cat’s claw were equally protective against peroxynitrite and H2O2, but green tea was 19B 120B 120B 120B 1203B 72 more effective than cat’s claw in reducing DPPH-induced apoptosis (P < 0.01). Necrotic cell death was marginally evident at these low concentrations of peroxynitrite and H2O2, and was attenuated both by cat’s claw and green tea (P < 0.01). In IEC-18 cells, all antioxidants were equally effective as antiapoptotic agents. CONCLUSIONS: These results indicate that dietary antioxidants can limit epithelial cell death in response to oxidant stress. In the case of green tea and cat’s claw, the cytoprotective response exceed their inherent ability to interact with the injurious oxidant, suggestive of actions on intracellular pathways regulating cell death. PMID: 11749672 [PubMed - indexed for MEDLINE] 17. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Sheng Y, Li L, Holmgren K, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2001 Jul;8(4):275-82 The Uncaria tomentosa water extracts (C-Med-100) have been shown to enhance DNA repair, mitogenic response and leukocyte recovery after chemotherapy-induced DNA damage in vivo. In this study, the effect of C-Med-100 supplement was evaluated in a human volunteer study. Twelve apparently healthy adults working in the same environment were randomly assigned into 3 groups with age and gender matched. One group was daily supplemented with a 250 mg tablet containing an aqueous extract of Uncaria tomentosa of C-Med-100, and another group with a 350 mg tablet, for 8 consecutive weeks. DNA repair after induction of DNA damage by a standard dose of hydrogen peroxide was measured 3 times before supplement and 3 times after the supplement for the last 3 weeks of the 8 week-supplement period. There were no drug-related toxic responses to C-Med-100 supplement when judged in terms of clinical symptoms, serum clinical chemistry, whole blood analysis and leukocyte differential counts. There was a statistically significant decrease of DNA damage and a concomitant increase of DNA repair in the supplement groups (250 and 350 mg/day) when compared with non-supplemented controls (p < 0.05). There was also an increased tendency of PHA induced lymphocyte proliferation in the treatment groups. Taken together, this trial has confirmed the earlier results obtained in the rat model when estimating DNA repair enhancement by C-Med-100. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11515717 [PubMed - indexed for MEDLINE] 18. Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test. Mohamed AF, Matsumoto K, Tabata K, Takayama H, Kitajima M, Watanabe H. Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan. The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to 73 attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the antiamnesic effect of uncarine E. PMID: 11197086 [PubMed - indexed for MEDLINE] 126B 19. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa. Sheng Y, Bryngelsson C, Pero RW. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] J Ethnopharmacol. 2000 Feb;69(2):115-26. Female W/Fu rats were gavaged daily with a water-soluble extract (C-MED-100) of Uncaria tomentosa supplied commercially by CampaMed at the doses of 0, 5, 10, 20, 40 and 80 mg/kg for 8 consecutive weeks. Phytohemagglutinin (PHA) stimulated lymphocyte proliferation was significantly increased in splenocytes of rats treated at the doses of 40 and 80 mg/kg. White blood cells (WBC) from the C-MED100 treatment groups of 40 and 80 mg/kg for 8 weeks or 160 mg/kg for 4 weeks were significantly elevated compared with controls (P < 0.05). In a human volunteer study, C-MED-100 was given daily at 5 mg/kg for 6 consecutive weeks to four healthy adult males. No toxicity was observed and again, WBC were significantly elevated (P < 0.05) after supplement. Repair of DNA single strand breaks (SSB) and double strand breaks (DSB) 3 h after 12 Gy whole body irradiation of rats were also significantly improved in C-MED-100 treated animals (P < 0.05). The LD50 and MTD of a single oral dose of CMED-100 in the rat were observed to be greater than 8 g/kg. Although the rats were treated daily with U. tomentosa extracts at the doses of 10-80 mg/kg for 8 weeks or 160 mg/kg for 4 weeks, no acute or chronic toxicity signs were observed symptomatically. In addition, no body weight, food consumption, organ weight and kidney, liver, spleen, and heart pathological changes were found to be associated with C-MED-100 treatment. PMID: 10687868 [PubMed - indexed for MEDLINE] 127B 128B 129B 120B 12B 12B 20. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa. Sheng Y, Pero RW, Wagner H. Department of Cell and Molecular Biology, University of Lund, Sweden. [email protected] Phytomedicine. 2000 Apr;7(2):137-43. The Uncaria tomentosa water extracts (C-Med-100) depleted of indole alkaloids (< 0.05%, w/w) have been shown to induce apoptosis and inhibit proliferation in tumor cells in vitro and to enhance DNA repair, mitogenic response and white blood cells in vivo. In this study, the effect of C-Med-100 in the treatment of chemically induced leukopenia was evaluated in a rat model. W/Fu rats were treated first with doxorubicin (DXR) 2 mg/kg x 3 (i.p. injection at 24 hour-intervals) to induce leukopenia. Twentyfour hours after the last DXR treatment, the rats were daily gavaged with C-Med-100 for 16 consecutive days. As a positive control, Neupogen, a granulocyte colony stimulator was also administered by subcutaneous injection at a dose of 5 and 10 microg/ml for 10 consecutive days. The results showed that both C-Med-100 and Neupogen treatment groups recovered significantly sooner (p < 0.05 by Duncan test) than DXR group. However, the recovery by C-Med-100 treatment was a more natural process than Neupogen because all fractions of white blood cells were proportionally increased while Neupogen mainly elevated the neutrophil cells. These results were also confirmed by microscopic examination of the blood smears. The mechanism of the C-Med-100 effect on WBC is not known but other data showing enhanced effects on DNA repair and immune cell proliferative response support a general immune enhancement. PMID: 10839217 [PubMed - indexed for MEDLINE] 123B 124B 125B 126B 127B 128B 74 21. Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100. Lamm S, Sheng Y, Pero RW. Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. Phytomedicine. 2001 Jul;8(4):267-74 A human intervention study was carri ed out using male volunteers attending a General Practice Clinic in New York City involving comparison of individuals supplemented with 350 mg x 2 C-Med-100 daily dose for two months with untreated controls for their abilities to respond to a 23 valent pneumococcal vaccine. C-Med-100 is a novel nutraceutical extract from the South American plant Uncaria tomentosa or Cat’s Claw which is known to possess immune enhancing and antiinflammatory properties in animals. There were no toxic side effects observed as judged by medical examination, clinical chemistry and blood cell analysis. However, statistically significant immune enhancement for the individuals on CMed-100 supplement was observed by (i) an elevation in the lymphocyte/neutrophil ratios of peripheral blood and (ii) a reduced decay in the 12 serotype antibody titer responses to pneumococcal vaccination at 5 months. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11515716 [PubMed - indexed for MEDLINE] 22. In vitro Effects of Two Extracts and Two Pure Alkaloid Preparations of Uncaria tomentosa on Peripheral Blood Mononuclear Cells. Winkler C, Wirleitner B, Schroecksnadel K, Schennach H, Mur E, Fuchs D. Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria. Planta Med. 2004 Mar;70(3):205-10. In the traditional Peruvian medicine, hot aqueous extracts of Uncaria tomentosa have been used for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. Some of the beneficial effects observed in patients suggest an immunomodulatory capacity of Uncaria tomentosa extracts. In this study, the effects of two extracts and two mixtures of tetracyclic and pentacyclic oxindole alkaloids of Uncaria tomentosa were investigated in freshly isolated human peripheral blood mononuclear cells (PBMC) stimulated with the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) in vitro. Neopterin production and tryptophan degradation were monitored in culture supernatants to determine the effects of the test substances on immunobiochemical pathways induced by interferon-gamma. Compared to unstimulated cells PHA and Con A increased the production of neopterin and degradation of tryptophan (p < 0.01). HCl and ethanol extracts and mixtures of alkaloids of Uncaria tomentosa inhibited both effects in a dose-dependent manner, the lowest effective concentrations of the extracts were 500 - 1000 microg/mL and of the alkaloid mixtures 100 - 175 microg/mL (p < 0.05 and < 0.01). With the highest concentrations of extracts and mixtures complete suppression of mitogen-induced neopterin production and tryptophan degradation was observed. These data demonstrate that Uncaria tomentosa extracts and mixtures of alkaloids modulate the immunobiochemical pathways induced by interferon-gamma. The findings imply a potential application of the extracts as immunoregulators and would be in line with observations in patients using these extracts. Abbreviations. Con A:concanavalin A EDTA:ethylenediaminetetraacetic acid, Titriplex III IDO:indoleamine (2,3)-dioxygenase IFN-gamma:interferon-gamma kyn:kynurenine MTT:3-(4,5dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide PBMC:peripheral blood mononuclear cells PHA:phytohaemagglutinin POA:pentacyclic oxindole alkaloids ROS:reactive oxygen species TOA:tetracyclic oxindole alkaloids trp:tryptophan PMID: 15114496 [PubMed - in process] 75 OTHER RESEARCH: 124B There are two species of Cat's Claw, Uncaria tomentosa and Uncaria guianensis, each having different properties and uses. The two are frequently confused but U. tomentosa is the more heavily researched for medicinal use[2] and immune modulation, while U. guianensis may be more useful for osteoarthritis.[3] U. tomentosa is further divided into two chemotypes with different properties and active compounds, a fact ignored by most manufacturers[4] that can have significant implications on both its use as an alternative medicine and in clinical trials to prove or disprove its efficacy.[5] 1243B Medicinal uses The parts used medicinally include the inner bark and root, taken in the form of capsules, tea and extract. U. tomentosa is used in nootropic drugs, as well as in treatment of cancer and HIV infection. It contains several alkaloids that are responsible for its overall medical effects, as well as tannins and various phytochemicals.[6] The chemotype of the plant determines the dominant type of alkaloid it produces, and thus its properties in vivo. One chemotype has roots which produce mostly the pentacyclic alkaloids that are responsible for the immunestrengthening effects desired by most consumers. The second chemotype produces tetracyclic oxindole alkaloids known as rhynchophylline and isorhynchophylline which counteract the immune-strengthening actions of the pentacyclic alkaloids, reduces the speed and force of the heart's contraction, and in high doses produce ataxia, lack of coordination and sedative effects.[5] Since U. tomentosa comes in at least these two different chemotypes, without chemical testing it is impossible to know which chemical compounds will predominate in a plant collected randomly from a natural setting. Some ingredients appear to act as anti-inflammatory, antioxidant and anticancer agents.[6] As an herbal treatment, Cat's Claw is used to treat intestinal ailments such as Crohn's disease, gastric ulcers and tumors, parasites, colitis, gastritis, diverticulitis and leaky bowel syndrome, while manufacturers claim that U. tomentosa can also be used in the treatment of AIDS in combination with AZT, the treatment and prevention of arthritis and rheumatism, diabetes, PMS, chronic fatigue syndrome, prostate conditions,[7] immune modulation,[8] Lyme disease[9] and systemic lupus erythematosus.[10] A 2005 review of the scholarly literature on Cat's Claw indicates there is supporting evidence toward its use in treating cancer, inflammation, viral infection and vascular conditions, and for its use as an immunostimulant, antioxidant, antibacterial and CNSrelated agent.[6] It has also been shown to be a powerful MAO-B inhibitor. [11] 124B 1245B 1246B 1247B 1248B Indigenous use The indigenous peoples of South and Central America have used U. tomentosa for medicinal purposes for two thousand years or more, It is often added to Ayahuasca. Researchers have investigated the use of the plant by the Asháninka tribe of Peru, who use the plant as a general health tonic, contraceptive, anti-inflammatory agent for the gastrointestinal tract, and as a treatment for diarrhea, rheumatic disorders, acne, diabetes, cancer and diseases of the urinary tract.[12] In Brazilian traditional medicine it is used against dengue to reduce inflammation and DOES NOT prevent dengue.[13] 1249B 1250B Allergies Individuals allergic to plants in the Rubiaceae family and different species of Uncaria may be more likely to have allergic reactions to Cat's Claw.[14] Reactions can include itching, rash and allergic inflammation of the kidneys. In one documented case, kidney failure occurred in a patient with Lupus erythematosus[15] but it is not known if this was due to an allergic reaction or another cause. There are other plants which are known as cat's claw (or uña de gato) in Mexico and Latin America; however, they are entirely different plants, belonging to neither the Uncaria genus, nor to the Rubiaceae family. Some of the Mexican uña de gato varieties are known to have toxic properties. 125B 125B 1253B 76 Footnotes 1. "Species Information". sun.ars-grin.gov. http://sun.arsgrin.gov:8080/npgspub/xsql/duke/plantdisp.xsql?taxon=1972. Retrieved on 2008-03-01. 2. Gattuso, M., Di Sapio, O., Gattuso, S. & Li Pereyra, E. (2004). Morphoanatomical studies of Uncaria tomentosa and Uncaria guianensis bark and leaves. Phytomedicine, 11, 213–223. 3. Piscoya J, Rodriguez Z, Bustamante SA, et al. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001;50:442–448. 4. Keplinger, K., Laus, G., Wurm, M., Dierich, M.P. & Teppner, Herwig. (1999). Uncaria tomentosa (Willd.) DC.—Ethnomedicinal use and new pharmacological, toxicological and botanical results. Journal of Ethnopharmacology, 64, 23–34. Available on-line as a PDF 5. ab 6. abc Nutrition Forum article by Varro E. Tyler on Cat's Claw Heitzman, M.E., Neto, C.C., Winiarz, E., Vaisberg, A.J. & Hammon, G.B. (2005). Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry, 66(1), 5-29. PMID 15649507 7. NutraSanus article on Cat's Claw 8. Information on Cat's Claw 9. Treatment of Lyme disease with Cat's Claw 10. Cat's claw used to treat Lupus erythematosus 11. [1] ^ The Longwood Herbal Task Force article on Cat's Claw 12. [2] ^ Intelihealth article discussing uses and dangers of Cat's Claw 13. Hilepo JN, Bellucci AG, Mossey RT. (1977). Acute renal failure caused by 'cat's claw' herbal remedy in a patient with systemic lupus erythematosus. Nephron, 77(3) pg. 361. 14. References 15. Germplasm Resources Information Network: Uncaria tomentosa 16. External links 17. Webpage on Cat's Claw with a library of scientific abstracts organized by year 18. Uncaria tomentosa List of Chemicals (Dr. Duke's Databases) UNIVERSITY OF MARYLAND MEDICAL CENTER RESEARCH: Named after its hook-like horns, cat's claw (Uncaria tomentosa) is a woody vine native to the Amazon rainforest and other tropical areas of South and Central America. The bark and root of this herb have been used by South Americans since the Inca civilization to treat a variety of health problems, including arthritis, stomach ulcers, inflammation, dysentery, and fevers. It was also used as a form of birth control. 77 Test tube studies indicate that cat's claw may stimulate the immune system, help relax the smooth muscles (such as the intestines), dilate blood vessels (helping lower blood pressure), and act as a diuretic (helping rid the body of excess water). It also has antioxidant properties, helping rid the body of particles known as free radicals that damage cells. Preliminary studies show it may have antitumor and anticancer effects as well. 1275B Osteoarthritis Although few scientific studies have investigated the safety and usefulness of this herb, it has been used traditionally to treat osteoarthritis (OA). One study indicates that it may help relieve pain from knee OA without side effects. 1276B 127B Rheumatoid arthritis Cat's claw has been suggested as a treatment for rheumatoid arthritis (RA) because of its anti-inflammatory properties. One small study showed a positive effect when cat's claw was taken by people who were also taking sulfasalazine or hydroxychloroquine to treat RA. Although cat's claw may help reduce inflammation, there is no evidence to show that it stops the progression of the disease. For that reason, RA should be treated with conventional medications, which can put the disease into remission. 1278B 1279B Further research Cat's claw is being studied for a number of other possible uses, including HIV, Chron's disease, multiple sclerosis, systemic lupus erythematosus (SLE or lupus), and Alzheimer's disease. More research is needed before scientists can say whether it is effective. 1280B 128B Plant Description: Cat's claw is a thorny vine that can climb as high as 100 feet. It grows primarily in the Amazon rainforest as well as tropical areas in South and Central America. Much of the cat's claw sold in the United States was grown in Peru. Cat's claw got its name from the curved, claw-like thorns that grow on its stem. The root and bark of cat's claw are the parts used for medicinal purposes. 128B 1283B 1284B What's It Made Of?: Cat's claw contains many types of plant chemicals that help reduce inflammation (such as tannins and sterols) and combat certain viruses (such as quinovic acid glycosides). Cat's claw preparations are made from the root and bark of the cat's claw vine. The effectiveness of the root and bark varies depending upon what time of year that portion of the plant is harvested. 1285B 1286B 1287B Available Forms: The bark of the cat's claw vine can be crushed and used to make tea. Standardized root and bark extracts (containing 3% alkaloids and 15% phenols) are also available in either liquid or capsule forms. 128B 1289B How to Take It: Pediatric There are no known scientific reports on the pediatric use of cat's claw. Do not give a child cat's claw without the supervision of your doctor. 1290B 129B 129B Adult Dry, encapsulated standardized extract: 100 mg per day for osteoarthritis; 250 - 350 mg per day for immune support Precautions: The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, you should take herbs with care, under the supervision of a health care practitioner. 1293B 1294B 1295B 1296B 78 Cat's claw appears to have few side effects. However, there have not been enough scientific studies of cat's claw to fully determine its safety. Some people have reported dizziness, nausea, and diarrhea when taking cat's claw. The diarrhea or loose stools tend to be mild and go away with continued use of the herb. Cat's claw may cause miscarriage and should not be taken by pregnant or nursing women. People with autoimmune diseases, skin grafts, tuberculosis, or those receiving organ transplants should not use cat's claw because of its possible effects on the immune system. Possible Interactions: If you are currently taking any of the following medications, you should not use cat's claw without first talking to your health care provider. Immunosuppressive medications -- In theory, because cat's claw may stimulate the immune system, it should not be used with medications intended to suppress the immune system, such as cyclosporin or other medications prescribed following an organ transplant or to treat an autoimmune disease. NSAIDs -- Cat's claw may protect against gastrointestinal damage associated with nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin) and naproxen (Aleve). Other medications -- Cat's claw may interact with the following medications: Anticoagulants (blood-thinning medication) Diuretics (water pills) Estrogens or progestins, including birth control pills Antihypertensive (blood pressure) medication Alternative Names: Una de gato; Uncaria tomentosa Reviewed last on: 11/11/2008 1. Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network. 2. Supporting Research 3. Aquino R, De Feo V, De Simone F, et al. New compounds and anti-inflammatory activity of Uncaria tomentosa. J Nat Prod. 1991;54: 453-459. 4. Gonzales GF, Valerio LG. Medicinal plants from Peru: a review of plants as potential agents against cancer. Anticancer Agents Med Chem. 2006;6(5):429-44. 5. Hardin SR. Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007 Feb;13(1):25-8. 6. Karch SB. The Consumer's Guide to Herbal Medicine. Hauppauge, New York: Advanced Research Press; 1999:55-56. 7. Keplinger K, Laus G, Wurm M, et al. Uncaria tomentosa (Willd.) Dethnomedicinal use and new pharmacological, toxicological and botanical results. J Ethnopharmacol. 1999;64:23-34. 8. Lemaire I, Assinewe V, Cano P, et al. Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa. J Ethnopharmacol. 1999;64:109-115. 79 9. Mur E, Hartig F, Eibl G, et al. Randomized double blind trial of an extract from the pentacyclic alkaloidchemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002 Apr;29(4):678-81. 139B 10. Pilarski R, Zielinski H, Ciesiolka D, et al. Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC. J Ethnopharmacol. 2006 Mar 8;104(1-2):18-23. 1320B 11. Piscoya J, Rodriguez Z, Bustamante SA, et al. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001;50(9):442-448. 132B 12. Rizzi R, Re F, Bianchi A, et al. Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. J Ethnopharmacol. 1993;38(1):63-77. 132B 13. Rotblatt M, Ziment I. Evidence-Based Herbal Medicine. Philadelphia, PA: Hanley & Belfus, Inc; 2002:114-118. 132B 14. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med. 2000;29(1):71-78. 1324B 15. Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Semin Arthritis Rheum. 2005 Jun;34(6):773-84. Review. 1325B 16. Sheng Y, et al. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa. Anticancer Res. 1998;18:3,363-3,368. 1326B 17. Sheng Y, Pero RW, Wagner H. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa. Phytomedicine. 2000;7(2):137-143. 1327B 18. Spelman K, Burns J, Nichols D, et al. Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators. Altern Med Rev. 2006 Jun;11(2):128-50. Review. 1328B 19. Steinberg PN. Cat's claw: medicinal properties of this Amazon vine. Nutrition Science News. 1995. 1329B ADDITONAL RESEARCH: Medical Botany, Lewis et al., published 1977 by John Wiley & Sons (NY), pp 277-279 and 509.* . Mark JS Miller et al., Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis, BMC Comp and Alternative Med Dec. 2001, I:II, U.S. . M. Sandoval et al., Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are indept . . . , Phytomedicine 9:325-337, 2002, U.S. . J Piscoya et al., Efficacy and safety of freeze-dried cat's claw in osteorarthritis of the knee: mechanisms . . . , Inflamm.res.50(2001) 442-448, U.S. . M Sandoval et al., Cat's Claw Inhibits TNalpha Prod. and Scavenges Free Radicals: Role in Cytoprotection, Free Radical Biology & Med, vol. 29 No. 1 pp 71-78,2000, U.S. . R Aquino et al, New quinovic acid glycosides from Uncaria Tomentosa, J Natural Prod, vol. 51, No. 2, pp 257261, Mar.-Apr. 1998, U.S. . G Konwalinka, Capillary electrophoretic analysis of oxidole alkaloids from Uncaria tomentosa, J of Chromatography, 609 (1992) pp 375-380, U.S. . H Stuppner et al, HPLC Analysis of the Main Oxidole Alkaloids from Uncaria tomentosa, Chromatography, V 34, No 11/12, Dec. 1992, U.S. . G. Laus et al., Separation of Stereoisomeric oxidole alkaloids from Uncaria tomentosa by high performance liquid chromatography, J Chromatography, A, 662 (1994) U.S. . 130B 13B 132B 13B 134B 135B 136B 137B 138B 139B 80 Y Sheng et al, Induction of Apoptosis and Inhibition of Proliferation of Human Tumor Cells Treated with Extracts of Uncaria Tomentosa, Anticancer Research 18:3363-3368 (1998). . M Sandoval-Chacon, Antiinflammatory actions of cat's claw: the role of NF-.kappa.B, Aliment Pharmacol Ther 1998;12;1279-1289 U.S. . K Keplinger et al, Uncaria tomentosa (Willd.) DC.-Ethnomedicinal use and new pharmacological, toxicological and botanical results, J Ethnopharmacology 64 (1999) 23-34 U.S. . Y Sheng et al, Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa, J Ethnopharmacology 69 (2000) 115-126 US. . S Lamm, Persistant response to pneumococcal vaccine in individuals supplemented with a novel water soluable extract of Uncaria tomentosa, C-MED-100.RTM. Phytomedicine, vol. 8(4) pp. 267-274 U.S., no date provided. THE UNIVERSITY OF TEXAS CENTER FOR ALTERNATIVE MEDICINE RESEARCH: (UT-CAM) CATS CLAW Other Common Names: Una de gato, Uncaria tomentosa Range: South and Central America, Andes mountains, particularly in Peru. Habitat: Rain forest. The Spanish name for it is "Una de gato". The name comes from the claw like features of the plant vines that resemble cat's claws. The inner bark of the vine is thought to contain the medicinal properties and therefore, is used to treat the following conditions: arthritis, gastritis, asthma, gastric ulcer, diabetes, cancer and tumors, viral infections, menstrual disorders, convalescence, rheumatism, general debility, gonorrhea, stimulate the immune system, and to promote wound healing. According to Ramon Ferreyra, Ph.D., a Harvard-educated botanist and professor at San Marcos University in Lima, Peru and the President of the Peruvian Botanical Society, states that twelve herbs in Peru are identified as Una de gato or cat’s claw. The herb of primary interest to alternative medicine researchers is Uncaria tomentosa, a woody vine that grows 1100 feet or more. The active constituents of Uncaria tomentosa may be a group of alkaloids with immune stimulating activity. Recent reports have demonstrated Uncaria’s role in improving immunity in cancer patients as well as its antimutagenic properties. All the individual alkaloids of Uncaria tomentosa with the exception of rynchophylline and mitraphylline have immunostimulant properties and the ability to enhance phagocytosis in vitro. Cat's claw is available as a tincture, capsules, tablets, elixirs, and as a cream. It may also be used as a tea. It can also be found mixed with other herbal therapies such as aloe. Known Hazards: This product should not be taken if you have an autoimmune disease, multiple sclerosis, or tuberculosis. In Europe, health care providers avoid combining this herb with hormonal drugs, insulin, or vaccines. Do not take this product if you are pregnant or breast-feeding. Cat's claw may block platelets from forming clots, so you should be cautious if you are already taking a medication, including aspirin, which thins the blood. A word of caution for the prospective buyers of cat’s claw: another plant also known as cat’s claw, (botanical name-Acacia gregii), grows along the Northern Mexico and Southern Texas border. People are purchasing this plant mistakenly believing it to be the Peruvian medicinal plant. This plant may be poisonous and is thought to contain a cyanide-based chemical compound. The Peruvian cat’s claw has a cinnamon colored bark; whereas, the South Texas plant comes from a shrub and so contains little twigs and leaves. The University of Texas Center for Alternative Medicine Research (UT-CAM) PUBMED/MEDLINE SUPPLEMENTAL RESEARCH Cat’s Claw acts as an immune stimulant and an adjunctive therapy for cancer (to reduce side effects of chemotherapy and protect cells); as a bowel cleanser and anti-inflammatory for Crohn's, colitis, diverticulitis, irritable bowel syndrome (IBS), and other bowel problems; as an anti-inflammatory for arthritis (all kinds) and 81 muscle pains/strains/injuries; as a general daily tonic (to tone, balance, and strengthen all body functions); for stomach ulcers and ulcerative colitis and as an ulcer preventative/ stomach and bowel protector) Contraindications: Cat's claw has been documented with immunostimulant effects and is contraindicated before or following any organ or bone marrow transplant or skin graft. Cat's claw has been documented with antifertility properties and is contraindicated in persons seeking to get pregnant. Cat's claw has been documented with chemicals which can reduce platelet aggregation and thin the blood. It is contraindicated in persons with bleeding disorders such as hemophilia. 1359B 1360B 136B 1362B Drug Interactions: Based upon animals studies, cat's claw may protect against gastrointestinal damage associated with NSAIDs such as ibuprofen. May potentiate coumadin and blood-thinning drugs. 136B Other Practitioner Observations: Cat's claw requires sufficient stomach acid to help break down the tannins and alkaloids during digestion and to aid in absorption. Avoid taking capsules at the same time as antacids. Large dosages of cat's claw (3-4 gram dosages) have been reported to cause some abdominal pain or gastrointestinal problems including diarrhea (due to the tannin content of the vine bark). The diarrhea or loose stools tend to be mild and go away with continued use. Discontinue use or reduce dosage if diarrhea persists longer than 3-4 days. 1364B 1365B 136B All available third-party research on cat's claw can be found at PubMed/Medline. A partial listing of the published research on cat's claw is shown below: 1367B Immunostimulant & Immunomodulatory Actions: 1. Spelman, K., et al. "Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators." Altern. Med. Rev. 2006 Jun; 11(2): 128-50. 1368B 1369B 2. Eberlin, S., et al. “Uncaria tomentosa extract increases the number of myeloid progenitor cells in the bone marrow of mice infected with Listeria monocytogenes.” Int. Immunopharmacol. 2005; 5(78):1235-46. 1370B 3. Deharo, E., et al. ”In vitro immunomodulatory activity of plants used by the Tacana ethnic group in Bolivia.” Phytomedicine. 2004 Sep; 11(6): 516-22. 137B 4. Lamm, S., et al, “Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100." Phytomedicine. 2001; 8(4): 267–74. 1372B 5. Sheng Y, et al., “Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa.” Phytomedicine. 2000; 7(2): 137–43. 137B 6. Lemaire, I., et al. “Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (una de gato).” J. Ethnopharmacol. 1999; 64(2): 109–15. 1374B 7. Marina, M. D. “Evaluacion de la actividal immunoestimulante de Uncaria tomentosa (Willd.) DC. Una de gato en ratones albinos." Biodiversidad Salud. 1998; 1(1): 16–19. 1375B 8. Keplinger, H., et al. “Oxindole alkaloids having properties stimulating the immunologic system and preparation containing same.” United States patent 5,302,611; April 12, 1994 1376B 82 9. Wagner, H., et al. “Die Alkaloide von Uncaria tomentosa und ihre Phagozytose-steigernde Wirkung." Planta Med. 1985; 51: 419–23. 10. Hemingway, S. R. and J. D. Phillipson. “Alkaloids from South American species of Uncaria (Rubiaceae)." J. Pharm. Pharmacol. 1974 suppl.; 26: 113p. Anti-inflammatory Actions: 1. Hardin, S. R. "Cat's claw: An Amazonian vine decreases inflammation in osteoarthritis." Complement. Ther. Clin. Pract. 2007 Feb; 13(1): 25-8. 2. Allen-Hall, L., et al. "Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates the expression if IL-1beta and TNF-alpha." J. Ethnopharmacol. 2007 Jan; 109(2): 312-7. 3. Miller, M. J., et al. "The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta." BMC Complement. Altern. Med. 2006 Apr; 6: 13. 4. Miller, M. J., et al. "Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711]." J. Inflamm. 2005 Oct; 2:11. 5. Valerio, L. G., et al. "Toxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii): a critical synopsis." Toxicol. Rev. 2005; 24(1): 11-35. 6. Setty, A. R., et al. "Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects." Semin. Arthritis Rheum. 2005; 34(6): 773-84. 7. Sheng, Y., et al. “An active ingredient of Cat's Claw water extracts: identification and efficacy of quinic acid.” J. Ethnopharmacol. 2005 Jan 15; 96(3): 8. Aguilar, J. L., et al. “Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae).” J. Ethnopharmacol. 2002; 81(2): 271–76. 9. Sandoval, M., et al., “Anti-inflammatory and antioxidant activities of cat’s claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content." Phytomedicine. 2002; 9(4): 325–37. 10. Mur, E., et al. “Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis.” J. Rheumatol. 2002 Apr; 29(4): 678–81. 11. Sandoval-Chacon, M., et al. “Anti-inflammatory actions of cat’s claw: the role of NF-kappaB.” Aliment. Pharmacol. Ther. 1998; 12(12): 1279–89. 12. Recio, M. C., et al. “Structural requirements for the anti-inflammatory activity of natural triterpenoids.” Planta Med. 1995; 61(2): 182–85. 13. Aquino, R., et al. “Plant metabolites. New compounds and anti-inflammatory activity of Uncaria tomentosa." J. Nat. Prod. 1991; 54: 453–59. 14. Cerri, R., et al. “New quinovic acid glycosides from Uncaria tomentosa." J. Nat. Prod. 1988; 51: 257– 61. 83 Anticancerous & Antitumor Actions: 1. Gonzales, G.F., et al. "Medicinal plants from Peru: a review of plants as potential agents against cancer." Anticancer Agents Med. Chem. 2006 Sep; 6(5): 429-44. 1394B 1395B 2. De Martino, L., et al. "Proapoptotic effect of Uncaria tomentosa extracts." J. Ethnopharmacol. 2006 Aug; 107(1): 91-4. 1396B 3. Bacher, N., et al. "Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1arrested and bcl-2-expressing acute lymphoblastic leukaemia cells." Br. J. Haematol. 2006 Mar; 132(5): 615-22. 1397B 4. Riva, L., et al. “The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line." Anticancer Res. 2001; 21(4A): 2457–61. 1398B 5. Muhammad, I., et al. “Investigation of Una de Gato I. 7-Deoxyloganic acid and 15N NMR spectroscopic studies on pentacyclic oxindole alkaloids from Uncaria tomentosa." Phytochemistry. 2001; 57(5): 781– 5. 139B 6. Sheng, Y., et al. “Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa." Anticancer Res. 1998; 18(5A): 3363–68. 140B 7. Salazar, E. L., et al. “Depletion of specific binding sites for estrogen receptor by Uncaria tomentosa." Proc. West. Pharmacol. Soc. 1998; 41(1): 123–124. 140B 8. Stuppner, H., et al. “A differential sensitivity of oxindole alkaloids to normal and leukemic cell lines.” Planta Med. (1993 suppl.); 59: A583. 1402B 9. Rizzi, R., et al. “Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts." J. Ethnopharmacol. 1993; 38: 63–77. 1403B 10. Peluso, G., et al. “Effetto antiproliferativo su cellule tumorali di estrattie metaboliti da Uncaria tomentosa. Studi in vitro sulla loro azione DNA polimerasi.” 11 Congreso Italo-Peruano de Etnomedicina Andina, Lima, Peru, October 27–30, 1993, 21–2. 140B 11. Rizzi, R., et al. “Bacterial cytotoxicity, mutagenicity and antimutagenicity of Uncaria tomentosa and its extracts. Antimutagenic activity of Uncaria tomentosa in humans." Premiere Colloque Européan d'Ethnopharmacologie, Metz, France, March 22–24, 1990. 1405B Cellular Protective & Antioxidant Actions: 1. Mammone, T., et al. "A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin." Phytother. Res. 2006; 20(3): 178-83. 1406B 1407B 2. Kuras, M., et al. "Changes in chromosome structure, mitotic activity and nuclear DNA content from cells of Allium Test induced by bark water extract of Uncaria tomentosa (Willd.) DC." J. Ethnopharmacol. 2006 Sep; 107(2):211-21. 1408B 3. Pilarski, R., et al. "Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC." J. Ethnopharmacol. 2006 Mar; 104(1-2): 18-23. 1409B 4. Cisneros, F. J., et al. “An Uncaria tomentosa (cat's claw) extract protects mice against ozone-induced lung inflammation.” J. Ethnopharmacol. 2005 Jan; 96(3): 355-64. 140B 84 5. Goncalves, C., et al. “Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity.” Phytochemistry. 2005; 66(1): 89-98. 6. Romero-Jimenez, M., et al. “Genotoxicity and anti-genotoxicity of some traditional medicinal herbs.” Mutat. Res. 2005 Aug; 585(1-2): 147-55. 7. Pilarski, R., et al. “Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC.” J. Ethnopharmacol. 2005 Sep 29; 8. Sheng, Y., et al. “DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study." Phytomedicine. 2001; 8(4): 275–82. 9. Sheng, Y., et al. “Enhanced DNA repair, immune function and reduced toxicity of C-Med-100, a novel aqueous extract from Uncaria tomentosa." J. Ethnopharmacol. 2000; 69(2): 115–26. 10. Sandoval, M., et al. “Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection.” Free Radic. Biol. Med. 2000; 29(1): 71–8. 11. Desmarchelier, C., et al. “Evaluation of the in vitro antioxidant activity in extracts of Uncaria tomentosa (Willd.) DC." Phytother. Res. 1997; 11(3): 254–256. 12. Chan-Xun, C., et al. “Inhibitory effect of rhynchophylline on platelet aggregation and thrombosis.” Acta Pharmacologica Sinica 1992; 13(2): 126–30. Actions on the Brain and Memory: 1. Jurgensen, S., et al. “Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa.” Pharmacol. Biochem. Behav. 2005 Jul; 81(3): 466-77. 2. Kang, T. H., et al. “Pteropodine and isopteropodine positively modulate the function of rat muscarinic M(1) and 5-HT(2) receptors expressed in Xenopus oocyte.” Eur. J. Pharmacol. 2002 May; 444(1-2): 3945. 3. Mohamed, A. F., et al. “ Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.” J. Pharm. Pharmacol. 2001; 52(12): 1553–61. 4. Roth, B. L., et al. “Insights into the structure and function of 5-HT(2) family serotonin receptors reveal novel strategies for therapeutic target development.” Expert Opin. Ther. Targets 2001 Dec; 5(6): 685695. 5. Castillo, G. "Methods of isolation of amyloid inhibitory ingredients within Uncaria tomentosa." US Patent No 7,029,710, April, 18, 2006. 6. Castillo, G. " Methods of isolating amyloid-inhibiting compounds and use of compounds isolated from Uncaria tomentosa and related plants." US Patent No. 6,929,808, August 16, 2005. 7. Castillo, G., et al. “Pharmaceutical compositions containing Uncaria tomentosa extract for treating Alzheimer's disease and other amyloidoses." Patent-Pct. Int. Paol. 1998; 00 33,659: 67pp. Antimicrobial Actions: 1. Kloucek, P., et al. “Antibacterial screening of some Peruvian medicinal plants used in Calleria District.” J. Ethnopharmacol. 2005 Jun; 99(2): 309-12. 85 2. Garcia, R., et al. “Antimicrobial activity of isopteropodine.” Z. Naturforsch. 2005; 60(5-6): 385-8. 3. Aquino, R., et al. “Plant metabolites. Structure and in vitro antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda." J. Nat. Prod. 1989; 4(52): 679–85. 4. Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJ, Sandoval M. Universidad Nacional Mayor de San Marcos, Facultad de Medicina, Lima, Peru. AIM: The purpose of this investigation was to evaluate the ability of cat's claw, an Amazonian medicinal plant, to treat osteoarthritis of the knee, collect safety and tolerance information and compare the antioxidant, and anti-inflammatory actions of Uncaria guianensis and Uncaria tomentosa in vitro. MATERIALS AND METHODS: Forty-five patients with osteoarthritis of the knee were recruited, 30 were treated with freeze-dried U guianensis, and 15 with placebo. Hematological parameters were assessed on entry and exit of the four-week trial. Pain, medical and subject assessment scores and adverse effects were collected at weeks 1, 2 and 4. The antioxidant and anti-inflammatory activity of the cat's claw species was determined by the alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) free radical scavenging method. Inhibition of TNFalpha and prostaglandin E2 (PGE2) production was determined in RAW 264.7 cells by ELISA. RESULTS: Cat's claw had no deleterious effects on blood or liver function or other significant side-effects compared to placebo. Pain associated with activity, medical and patient assessment scores were all significantly reduced, with benefits occurring within the first week of therapy. Knee pain at rest or at night, and knee circumference were not significantly reduced by cat's claw during this brief trial. In vitro tests indicated that U guianensis and U. tomentosa were equivalent at quenching DPPH radicals (EC50, 13.6-21.7 microg/ml) as well as inhibiting TNFalpha production. However, the latter action was registered at much lower concentrations (EC50, 10.2-10.9 ng/ml). Cat's claw (10 microg/ml) had no effect on basal PGE2 production, but reduced LPS-induced PGE2 release (P < 0.05), but at higher concentrations than that required for TNFalpha inhibition. CONCLUSION: Cat's claw is an effective treatment for osteoarthritis. The species, U guianensis and U tomentosa are equiactive. They are effective antioxidants, but their anti-inflammatory properties may result from their ability to inhibit TNFalpha and to a lesser extent PGE2 production. PMID: 11603848 [PubMed - indexed for MEDLINE] 1429B 1430B 143B 1432B 143B 143B Related articles 1. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002 May; 9(4):325-37. [Phytomedicine. 2002] 2. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med. 2000 Jul 1; 29(1):71-8. [Free Radic Biol Med. 2000] 3. ReviewCat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007 Feb; 13(1):25-8. Epub 2006 Dec 13. [Complement Ther Clin Pract. 2007] 4. ReviewToxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii) : a critical synopsis. Toxicol Rev. 2005; 24(1):11-35. [Toxicol Rev. 2005] 5. Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity. Phytochemistry. 2005 Jan; 66(1):89-98. [Phytochemistry. 2005] 6. Cited by 5 PubMed Central articles Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. 1435B 1436B 1437B 1438B 1439B 140B 14B 142B 143B 14B 145B 146B 147B 148B 149B 1450B 145B 1452B 86 Mehta K, Gala J, Bhasale S, Naik S, Modak M, Thakur H, Deo N, Miller MJ. BMC Complement Altern Med. 2007 Oct 31; 7:34. Epub 2007 Oct 31. [BMC Complement Altern Med. 2007] 7. ReviewOsteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Ameye LG, Chee WS. Arthritis Res Ther. 2006; 8(4):R127. [Arthritis Res Ther. 2006] The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta. Miller MJ, Ahmed S, Bobrowski P, Haqqi TM. BMC Complement Altern Med. 2006 Apr 7; 6:13. Epub 2006 Apr 7. [BMC Complement Altern Med. 2006] 8. Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ. Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Cat's claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat's claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat's claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 microg/ml, p <.05). Cat's claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat's claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat's claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha production. The primary mechanism for cat's claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis. PMID: 10962207 [PubMed - indexed for MEDLINE] 9. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002 May; 9(4):325-37. [Phytomedicine. 2002] 10. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001 Sep; 50(9):442-8. [Inflamm Res. 2001] 11. ReviewToxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii) : a critical synopsis. Toxicol Rev. 2005; 24(1):11-35. [Toxicol Rev. 2005] 12. ReviewCat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007 Feb; 13(1):25-8. Epub 2006 Dec 13. [Complement Ther Clin Pract. 2007] 13. Antiinflammatory actions of cat's claw: the role of NF-kappaB. Aliment Pharmacol Ther. 1998 Dec; 12(12):1279-89. [Aliment Pharmacol Ther. 1998] Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis. Hardin SR. University of North Carolina at Charlotte, School of Nursing 87 Cat's claw (Uncaria tomentosa and Uncaria guianesis) is a medicinal plant from the Amazon commonly used to treat disorders such as arthritis, gastritis and osteoarthritis. The mechanism of cat's claw appears to be as an inhibitor of TNFalpha and antioxidant. Understanding the processes in osteoarthritis may facilitate and clarify the potential role of cat's claw as a complementary therapy to assist in the reduction of pro-inflammatory mediators and effectors. The clinical relevance of this therapy as a viable modality of intervention will be discussed. 1482B Valerio LG Jr, Gonzales GF. Division of Biotechnology and GRAS Notice Review, Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, PMID: 16042502 [PubMed - indexed for MEDLINE] Recent exceptional growth in human exposure to natural products known to originate from traditional medicine has lead to a resurgence of scientific interest in their biological effects. As a strategy for improvement of the assessment of their pharmacological and toxicological profile, scientific evidence-based approaches are being employed to appropriately evaluate composition, quality, potential medicinal activity and safety of these natural products. Using this approach, we comprehensively reviewed existing scientific evidence for known composition, medicinal uses (past and present), and documented biological effects with emphasis on clinical pharmacology and toxicology of two commonly used medicinal plants from South America with substantial human exposure from historical and current global use: Uncaria tomentosa (common name: cat's claw, and Spanish: uña de gato), and Lepidium meyenii (common name: maca). Despite the geographic sourcing from remote regions of the tropical Amazon and high altitude Andean mountains, cat's claw and maca are widely available commercially in industrialised countries. Analytical characterisations of their active constituents have identified a variety of classes of compounds of toxicological, pharmacological and even nutritional interest including oxindole and indole alkaloids, flavonoids, glucosinolates, sterols, polyunsaturated fatty acids, carbolines and other compounds.The oxindole alkaloids from the root bark of cat's claw are thought to invoke its most widely sought-after medicinal effects as a herbal remedy against inflammation. We find the scientific evidence supporting this claim is not conclusive and although there exists a base of information addressing this medicinal use, it is limited in scope with some evidence accumulated from in vitro studies towards understanding possible mechanisms of action by specific oxindole alkaloids through inhibition of nuclear factor (NF)-kappaB activation. Although controlled clinical studies have demonstrated reduction in pain associated with cat's claw intake in patients with various chronic inflammatory disorders, there is insufficient clinical data overall to draw a firm conclusion for its anti-inflammatory effects. An important observation was that experimental results were often dependent upon the nature of the preparation used. It appears that the presence of unknown substances has an important role in the overall effects of cat's claw extracts is an important factor for consideration. The available animal toxicological studies did not indicate severe toxicity from oral intake of cat's claw preparations but rather were suggestive of a low potential for acute and subacute oral toxicity, and a lack of evidence to demonstrate genotoxic potential and mutagenic activity. Cat’s Claw has been widely studied as an anti-inflammatory, which has been attributed to its content of oxindolic alkaloids. These studies have been conducted in four hospitals in Peru: Lima, Callao, Ica and Huancayo, with 60 patients with classic Rheumatoid Arthritis. In a double blind test, 31 patients received 6 daily capsules of Cat’s Claw (Uncaria tomentosa) and another group of 29 patients received the same quantity of capsules containing a placebo. The study lasted 6 months, and they carried out an evaluation at the one month, three month and six month periods. The results revealed with stunning clarity that the patients who that Cat’s experienced a very significant improvement in morning stiffness, daily pain levels and a reduction in the number of inflamed joints. 1483B 148B 1485B 1486B 1487B For Pollen: 1. Aliyazicioglu Y, Deger O, Ovali E, et al. Effects of Turkish pollen and propolis extracts on respiratory burst for K-562 cell lines. Int Immunopharmacol 2005;5(11):1652-1657. 148B 1489B 2. Boppre M, Colegate SM, Edgar JA. Pyrrolizidine alkaloids of Echium vulgare honey found in pure pollen. J Agric Food Chem 2005;53(3):594-600. 1490B 88 3. Campos MG, Webby RF, Markham KR, et al. Age-induced diminution of free radical scavenging capacity in bee pollens and the contribution of constituent flavonoids. J Agric Food Chem 2003;51(3):742-745. 4. Garcia-Villanova RJ, Cordon C, Gonzalez Paramas AM, et al. Simultaneous immunoaffinity column cleanup and HPLC analysis of aflatoxins and ochratoxin A in Spanish bee pollen. J Agric Food Chem 2004;52(24):7235-7239. 5. Gonzalez G, Hinojo MJ, Mateo R, et al. Occurrence of mycotoxin producing fungi in bee pollen. Int J Food Microbiol 2005;105(1):1-9. 6. Greenberger PA, Flais MJ. Bee pollen-induced anaphylactic reaction in an unknowingly sensitized subject. Ann Allergy Asthma Immunol 2001;86(2):239-242. 7. Iarosh AA, Macheret EL, Iarosh AA, et al. [Changes in the immunological reactivity of patients with disseminated sclerosis treated by prednisolone and the preparation Proper-Myl]. Vrach Delo 1990;(2):83-86. 8. Iversen T, Fiirgaard KM, Schriver P, et al. The effect of NaO Li Su on memory functions and blood chemistry in elderly people. J Ethnopharmacol 1997;56(2):109-116. 9. Krivopalov-Moscvin I. Apitherapy in the rehabilitation of patients with multiple sclerosis -- XVI World Congress of Neurology. Buenos Aires, Argentina, September 14-19, 1997. Abstracts. J Neurol Sci 1997;150 Suppl:S264-367. 10. Lei H, Shi Q, Ge F, et al. [Supercritical CO2 extraction of fatty oils from bee pollen and its GC-MS analysis]. Zhong Yao Cai 2004;27(3):177-180. 11. Medina A, Gonzalez G, Saez JM, et al. Bee pollen, a substrate that stimulates ochratoxin A production by Aspergillus ochraceus Wilh. Syst Appl Microbiol 2004;27(2):261-267. 12. Ozcan M, Unver A, Ceylan DA, et al. Inhibitory effect of pollen and propolis extracts. Nahrung 2004;48(3):188-194. 13. Palanisamy A, Haller C, Olson KR. Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen. J Toxicol Clin Toxicol 2003;41(6):865-867. 14. Paola-Naranjo RD, Sanchez-Sanchez J, Gonzalez-Paramas AM, et al. Liquid chromatographic-mass spectrometric analysis of anthocyanin composition of dark blue bee pollen from Echium plantagineum. J Chromatogr A 2004;1054(1-2):205-210. 15. Wang J, Jin GM, Zheng YM, et al. [Effect of bee pollen on development of immune organ of animal]. Zhongguo Zhong Yao Za Zhi 2005;30(19):153216. Steben RE, Boudreaux P. The effects of pollen and protein extracts on selected blood factors and performance of athletes. J Sports Med 1978;18:221-6. 17. Small randomized study evaluating the effect of bee pollen supplement on 18 male high school students. Three treatment arms were established to compare bee pollen to protein extract to placebo. Following 12 weeks of training and supplementation, no effect of the bee pollen, protein extract, or placebo was seen on performance, hemoglobin, or serum electrolytes. This small study was probably incapable of detecting a statistically significant difference between treatment groups. No adverse events were reported with supplementation. 89 References 1. Mirkin G. Can bee pollen benefit health? JAMA 1989;262:1854. 1506B 1507B 2. DerMarderosian A, editor. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999. 1508B 3. Maughan RJ, Evans SP. Effects of pollen extract upon adolescent swimmers. Br J Sports Med. 1982 Sep;16(3):142-5. 1509B 4. Steben RE, Boudreaux P. The effects of pollen and protein extracts on selected blood factors and performance of athletes. J Sports Med Phys Fitness. 1978;18:221-6. 150B 5. Palanisamy A, Haller C, Olson KR. Photosensitivity reaction in a woman using an herbal supplement containing ginseng, goldenseal, and bee pollen. J Toxicol Clin Toxicol. 2003;41(6):865-7. 15B Read more: http://www.healthline.com/natstandardcontent/bee-pollen/3#ixzz1CCiHgS1V Healthline.com - Connect to Better Health Read more: http://www.healthline.com/natstandardcontent/bee-pollen#ixzz1CChJ4ENe healthline.com - Connect to Better Health 152B 153B 154B 15B For Achiote: 1. Dunham, N. W. et al. "A preliminary pharmacologic investigation of the roots of Bixa orellana." J. Amer. Pharm. Ass. Sci. Ed. 1960; 49: 218. Morrison, E. Y., et al. "Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies." Trop. Georg. Med. 1991; 43(2): 184-88. Morrison, E. Y., et al. "Toxicity of the hyperglycaemic-inducing extract of the annatto (Bixa orellana) in the dog." West Indian Med. J. 1985; 34(1): 38-42. Morrison, E. Y., et al. "The effect of Bixa orellana (annatto) on blood sugar levels in the anaesthetized dog." West Indian Med. J. (March 1985). 156B 157B 2. Terashima, S., et al. "Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas." Chem. Pharm. Bull. 1991; 39(12): 3346-47. 158B 3. Otero, R., et al. "Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of lethal and enzymatic effects of Bothrops atrox venom." J. Ethnopharmacol. 2000; 71(3): 505-11. 159B 4. Cáceres A., et al. "Antigonorrhoeal activity of plants used in Guatemala for the treatment of sexually transmitted diseases." J. Ethnopharmacol. (October 1995). 1520B 5. George, M., et al. "Investigations on plant antibiotics. Part IV. Further search for antibiotic substances in Indian medicinal plants." Indian J. Med. Res. 1949; 37: 169-81. 152B 6. Bressani, R., et al. "Chemical composition, amino acid content and nutritive value of the protein of the annatto seed (Bixa orellana L.)." Arch. Latinoam. Nutr. 33(2): 356-76. \ 152B 7. Scita, G. "Retinoic acid and beta-carotene inhibit fibronectin synthesis and release by fibroblasts; antagonism to phorbol ester." Carcinogenesis 15 (1994): 1043-48. 1523B 8. Zhang, L. X. "Carotenoids up-regulate connexin43 gene expression independent of their provitanin A or antioxidant properties." Cancer Res. 52 (1992): 5707-12. 1524B 90 9. Di Mascio, P. "Carotenoids, tocopherols and thiols as biological singlet molecular oxygen quenchers." Biochem. Soc. Trans. 18 (1990): 1054-6. 10. Hirose, S. "Energized state of mitochondria as revealed by the spectral change of bound bixin." Arch. Biochem. Biophys. 152 (1972): 36-43. 11. Inada, Y. "Spectral changes of bixin upon interaction with respiring rat liver mitochondria." Arch. Biochem. Biophys. 146 (1971): 366-67. 12. Campelo, C. R. "Contribuicao ao estudo das plantas medicinais no estado de alagoas III, VII." Simposio de Plantas Medicinais do Brasil, 1-3 de Setembro, 1982, Belo Horizonte-MG, 85m. 13. Nish, W. A., et al. "Anaphylaxis to annatto dye: a case report." Ann. Allergy 1991; 66(2): 129-31. MORE RESEARCH: 1. Cystitis, obesity, renal insufficiency, eliminate uric acid. Is very effective for Prostatitis and also for Vulgaris Acne Astringent, Nutritive, Emollient, Antibacterial, Antioxidant, Expectorant Antidysenteric for more information. 2. Terashima S, et al. Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas. Chem Pharm Bull (Tokyo), 1991 Dec 3. Morrison EY, et al. Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies. Trop Geogr Med, 1991 Jan-Apr 4. Nish WA, et al. Anaphylaxis to annatto dye: a case report. Ann Allergy, 1991 Feb 5. Morrison EY, et al. Toxicity of the hyperglycaemic-inducing extract of the annatto (Bixa orellana) in the dog. West Indian Med J, 1987 Jun 6. Morrison EY, et al. The effect of Bixa orellana (annatto) on blood sugar levels in the anaesthetized dog. West Indian Med J, 1985 Mar 7. Wurts ML, et al. [Analysis of the seed Bixa orellana, L. (annatto) and the waste generated in the extraction of its pigments] Arch Latinoam Nutr, 1983 Sep 8. Bressani R, et al. [Chemical composition, amino acid content and nutritive value of the protein of the annatto seed (Bixa orellana, L.)] Arch Latinoam Nutr, 1983 Jun 9. Ciscar F. Achiotin, an extract of achiote seeds (Bixa orellana L.), as a histologic stain for lipids. Stain Technol, 1965 Sep 10. Herbs Botanic's Dictionary Peru useful herbs by Antonio Brack Egg & PNUD & The Regional Andean Studies 07.07.01 ISBN 9972-691--21-0 11. 1 "Physiological studies and Determination of Chromosome Number in Maca, Lepidium meyenii" by Carlos Quiros, A. Epperson, J. Hu, and M. Holle. Econ Bot 50 (2) 216-223, 1996. “According to folk belief, maca enhances female fertility in humans and domestic animals which tends to be reduced at higher altitudes. For Zinc Sulphate: 91 1. Sandstead HH. Understanding zinc: recent observations and interpretations. J Lab Clin Med 1994;124:322-7. [PubMed abstract] 1543B 2. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001. 154B 3. Solomons NW. Mild human zinc deficiency produces an imbalance between cell-mediated and humoral immunity. Nutr Rev 1998;56:27-8. [PubMed abstract] 154B 4. Prasad AS. Zinc: an overview. Nutrition 1995;11:93-9. [PubMed abstract] 1546B 5. Heyneman CA. Zinc deficiency and taste disorders. Ann Pharmacother 1996;30:186-7. [PubMed abstract] 1547B 6. Simmer K, Thompson RP. Zinc in the fetus and newborn. Acta Paediatr Scand Suppl 1985;319:158-63. [PubMed abstract] 1548B 7. Fabris N, Mocchegiani E. Zinc, human diseases and aging. Aging (Milano) 1995;7:77-93. [PubMed abstract] 1549B 8. Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation. J Trace Elem Med Biol 2006;20:3-18. [PubMed abstract] 150B 9. Prasad AS, Beck FW, Grabowski SM, Kaplan J, Mathog RH. Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects. Proc Assoc Am Physicians 1997;109:68-77. [PubMed abstract] 15B 10. Rink L, Gabriel P. Zinc and the immune system. Proc Nutr Soc 2000;59:541-52. [PubMed abstract] 152B 11. U.S. Department of Agriculture, Agricultural Research Service. USDA Nutrient Database for Standard Reference, Release 14. [http://www.nal.usda.gov/fnic/foodcomp/search/] 153B 12. Sandstrom B. Bioavailability of zinc. Eur J Clin Nutr 1997;51 (1 Suppl):S17-9. [PubMed abstract] 154B 13. Wise A. Phytate and zinc bioavailability. Int J Food Sci Nutr 1995;46:53-63. [PubMed abstract] 15B 14. Jafek BW, Linschoten MR, Murrow BW. Anosmia after intranasal zinc gluconate use. Am J Rhinol 2004;18:137-41. [PubMed abstract] 156B 15. Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20. [PubMed abstract] 157B 16. U.S. Food and Drug Administration. Warnings on Three Zicam Intranasal Zinc Products. [http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm166931.htm] 158B 17. Alaimo K, McDowell MA, Briefel RR, Bischlf AM, Caughman CR, Loria CM, et al. Dietary Intake of Vitamins, Minerals, and Fiber of Persons Ages 2 Months and Over in the United States: Third National Health and Nutrition Examination Survey, Phase 1, 1988-91. Hyattsville, MD: Centers for Disease Control and Prevention, National Center for Health Statistics, 1994:1-28. 159B 18. Interagency Board for Nutrition Monitoring and Related Research. Third Report on Nutrition Monitoring in the United States. Washington, DC: U.S. Government Printing Office, 1995. 1560B 92 19. Ervin RB, Kennedy-Stephenson J. Mineral intakes of elderly adult supplement and non-supplement users in the third national health and nutrition examination survey. J Nutr 2002;132:3422-7. [PubMed abstract] 20. Ribar DS, Hamrick KS. Dynamics of Poverty and Food Sufficiency. Food Assistance and Nutrition Report Number 36, 2003. Washington, DC: U.S. Department of Agriculture, Economic Research Service. [http://www.ers.usda.gov/publications/fanrr36/fanrr36.pdf] 21. Dixon LB, Winkleby MA, Radimer KL. Dietary intakes and serum nutrients differ between adults from food-insufficient and food-sufficient families: Third National Health and Nutrition Examination Survey, 1988-1994. J Nutr 2001;131:1232-46. [PubMed abstract] 22. Prasad AS. Zinc deficiency: its characterization and treatment. Met Ions Biol Syst 2004;41:103-37. [PubMed abstract] 23. Wang LC, Busbey S. Images in clinical medicine. Acquired acrodermatitis enteropathica. N Engl J Med 2005;352:1121. [PubMed abstract] 24. Hambidge KM, Mild zinc deficiency in human subjects. In: Mills CF, ed. Zinc in Human Biology. New York, NY: Springer-Verlag, 1989:281-96. 25. King JC, Cousins RJ. Zinc. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins, RJ, eds. Modern Nutrition in Health and Disease, 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2005:271-85. 26. Krasovec M, Frenk E. Acrodermatitis enteropathica secondary to Crohn's disease. Dermatology 1996;193:361-3. [PubMed abstract] 27. Ploysangam A, Falciglia GA, Brehm BJ. Effect of marginal zinc deficiency on human growth and development. J Trop Pediatr 1997;43:192-8. [PubMed abstract] 28. Nishi Y. Zinc and growth. J Am Coll Nutr 1996;15:340-4. [PubMed abstract] 29. Hunt JR. Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am J Clin Nutr 2003;78 (3 Suppl):633S-9S. [PubMed abstract] 30. Van Wouwe JP. Clinical and laboratory assessment of zinc deficiency in Dutch children. A review. Biol Trace Elem Res 1995;49:211-25. [PubMed abstract] 31. Hambidge KM, Krebs NF. Zinc deficiency: a special challenge. J Nutr 2007;137:1101-5. [PubMed abstract] 32. Prasad AS. Zinc deficiency in women, infants and children. J Am Coll Nutr 1996;15:113-20. [PubMed abstract] 33. Naber TH, van den Hamer CJ, Baadenhuysen H, Jansen JB. The value of methods to determine zinc deficiency in patients with Crohn's disease. Scand J Gastroenterol 1998;33:514-23. [PubMed abstract] 34. Valberg LS, Flanagan PR, Kertesz A, Bondy DC. Zinc absorption in inflammatory bowel disease. Dig Dis Sci. 1986 Jul;31(7):724-31. [PubMed abstract] 35. Prasad AS. Zinc deficiency. BMJ 2003;326:409-10. [PubMed abstract] 93 36. American Dietetic Association, Dietitians of Canada. Position of the American Dietetic Association and Dietitians of Canada: vegetarian diets. J Am Diet Assoc 2003;103:748-65. [PubMed abstract] 1578B 37. Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr 1998;68 (2 Suppl):499S-508S. [PubMed abstract] 1579B 38. Krebs NF. Zinc supplementation during lactation. Am J Clin Nutr 1998;68 (2 Suppl):509S -12S. [PubMed abstract] 1580B 39. Brown KH, Allen LH, Peerson J. Zinc supplementation and children's growth: a meta-analysis of intervention trials. Bibl Nutr Dieta 1998;54:73-6. 158B 40. Leonard MB, Zemel BS, Kawchak DA, Ohene-Frempong K, Stallings VA. Plasma zinc status, growth, and maturation in children with sickle cell disease. J Pediatr 1998;132:467-71. [PubMed abstract] 1582B 41. Zemel BS, Kawchak DA, Fung EB, Ohene-Frempong K, Stallings VA. Effect of zinc supplementation on growth and body composition in children with sickle cell disease. Am J Clin Nutr 2002;75:300-7. [PubMed abstract] 1583B 42. Prasad AS. Zinc deficiency in patients with sickle cell disease. Am J Clin Nutr 2002;75:181-2. [PubMed abstract] 1584B 43. Kang YJ, Zhou Z. Zinc prevention and treatment of alcoholic liver disease. Mol Aspects Med 2005;26:391-404. [PubMed abstract] 158B 44. Menzano E, Carlen PL. Zinc deficiency and corticosteroids in the pathogenesis of alcoholic brain dysfunction—a review. Alcohol Clin Exp Res 1994;18:895-901. [PubMed abstract] 1586B 45. Navarro S, Valderrama R, To-Figueras J, Gimenez A, Lopez JM, Campo E, et al. Role of zinc in the process of pancreatic fibrosis in chronic alcoholic pancreatitis. Pancreas 1994;9:270-4. [PubMed abstract] 1587B 46. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 1998;68:447S-63S. [PubMed abstract] 158B 47. Wintergerst ES, Maggini S, Hornig DH. Contribution of selected vitamins and trace elements to immune function. Ann Nutr Metab 2007;51:301-23. [PubMed abstract] 1589B 48. Beck FW, Prasad AS, Kaplan J, Fitzgerald JT, Brewer GJ. Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. Am J Physiol 1997;272:E1002-7. [PubMed abstract] 1590B 49. Prasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 2000;182 (Suppl):S62-8. [PubMed abstract] 159B 50. Bahl R, Bhandari N, Hambidge KM, Bhan MK. Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting. Am J Clin Nutr 1998;68 (2 Suppl):414S-7S. [PubMed abstract] 1592B 51. Brooks WA, Santosham M, Naheed A, Goswami D, Wahed MA, Diener-West M, et al. Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, 1593B 94 low-income population in Bangladesh: randomised controlled trial. Lancet 2005;366:999-1004. [PubMed abstract] 52. Meydani SN, Barnett JB, Dallal GE, Fine BC, Jacques PF, Leka LS, et al. Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr 2007;86:1167-73. [PubMed abstract] 53. Black RE. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr 2003;133:1485S-9S. [PubMed abstract] 54. Lansdown AB, Mirastschijski U, Stubbs N, Scanlon E, Agren MS. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen 2007;15:2-16. [PubMed abstract] 55. Anderson I. Zinc as an aid to healing. Nurs Times 1995;91:68, 70. [PubMed abstract] 56. Wilkinson EA, Hawke CI. Does oral zinc aid the healing of chronic leg ulcers? A systematic literature review. Arch Dermatol 1998;134:1556-60. [PubMed abstract] 57. Wilkinson EA, Hawke CI. Oral zinc for arterial and venous leg ulcers. Cochrane Database Syst Rev 2000;(2):CD001273. [PubMed abstract] 58. World Health Organization and United Nations Children Fund. Clinical management of acute diarrhoea. WHO/UNICEF Joint Statement, August, 2004. [ http://www.unicef.org/nutrition/files/ENAcute_Diarrhoea_reprint.pdf] 59. Black RE. Therapeutic and preventive effects of zinc on serious childhood infectious diseases in developing countries. Am J Clin Nutr 1998;68:476S-9S. [PubMed abstract] 60. Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000;72:1516-22. [PubMed abstract] 61. Lukacik M, Thomas RL, Aranda JV. A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics 2008;121:326-36. [PubMed abstract] 62. Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis 2007;45 (1 Suppl):S73-7. [PubMed abstract] 63. Hulisz D. Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc (2003) 2004;44:594-603. [PubMed abstract] 64. Caruso TJ, Prober CG, Gwaltney JM Jr. Treatment of naturally acquired common colds with zinc: a structured review. Clin Infect Dis 2007;45:569-74. [PubMed abstract] 65. Prasad AS, Beck FW, Bao B, Snell D, Fitzgerald JT. Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate. J Infect Dis 2008 ;197:795-802. [PubMed abstract] 66. Turner RB, Cetnarowski WE. Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 2000;31:1202-8. [PubMed abstract] 95 67. Eby GA, Halcomb WW. Ineffectiveness of zinc gluconate nasal spray and zinc orotate lozenges in common-cold treatment: a double-blind, placebo-controlled clinical trial. Altern Ther Health Med 2006;12:34-8. [PubMed abstract] 1609B 68. Marshall I. Zinc for the common cold. Cochrane Database Syst Rev 2000;(2):CD001364. [PubMed abstract] 160B 69. Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 2006;(2):CD000254. [PubMed abstract] 16B 70. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119:1417-36. [PubMed abstract] 162B 71. van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 2005;294:3101-7. [PubMed abstract] 163B 72. Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH. Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis. BMJ 2007;335:755. [PubMed abstract] 164B 73. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E. Oral zinc in macular degeneration. Arch Ophthalmol 1988;106:192-8. [PubMed abstract] 165B 74. Stur M, Tittl M, Reitner A, Meisinger V. Oral zinc and the second eye in age-related macular degeneration. Invest Ophthalmol Vis Sci 1996;37:1225-35. [PubMed abstract] 16B 75. Whittaker P. Iron and zinc interactions in humans. Am J Clin Nutr 1998;68:442S-6S. [PubMed abstract] 167B 76. Broun ER, Greist A, Tricot G, Hoffman R. Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression. JAMA 1990;264:1441-3. [PubMed abstract] 168B 77. Willis MS, Monaghan SA, Miller ML, McKenna RW, Perkins WD, Levinson BS, et al. Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol 2005;123:125-31. [PubMed abstract] 169B 78. Lewis MR, Kokan L. Zinc gluconate: acute ingestion. J Toxicol Clin Toxicol 1998;36:99-101. [PubMed abstract] 1620B 79. Hooper PL, Visconti L, Garry PJ, Johnson GE. Zinc lowers high-density lipoprotein-cholesterol levels. J Am Med Assoc 1980;244:1960-1. [PubMed abstract] 162B 80. Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol 2007;177:639-43. [PubMed abstract] 162B 81. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. [PubMed abstract] 1623B 82. Penttilä O, Hurme H, Neuvonen PJ. Effect of zinc sulphate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4. [PubMed abstract] 1624B 96 83. Natural Medicines Comprehensive Database. Zinc. [http://www.NaturalDatabase.com] 84. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, Dick RD, Wang Y. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. [PubMed abstract] 85. Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. [PubMed abstract] Acne Treatment Zinc sulfate is believed to help heal blemishes caused by acne, according to Healthy-Skincare.com, as well as reduce inflammation. Further research is still needed, however, to establish a correlation between the amount of zinc in the body and its effects on treating acne breakouts. Dissolve Artery Blockages Increase Blood Flow Dramatically Safely Restore Cardio Health www.arteryhealth.co.uk Diarrhea Treatment Ongoing studies have shown that zinc sulfate may relieve the duration and severity of diarrhea, according to research from the FDA. It appears particularly effective when used by malnourished children, who typically suffer from zinc deficiency. Immune System Health & Wound Healing Zinc sulfate supplementation may help promote a healthy immune system, according to Vitamins-Nutrition.org. Zinc is vital in the production of T-cells, which help fight infections. A strong immune system supported through healthy zinc levels ensure that infections and open wounds heal quickly. Sickle Cell Anemia Treatment Symptoms of sickle cell anemia may be managed better through zinc sulfate supplementation, due to the zinc deficiency many sickle cell patients suffer, according to The American Journal of Clinical Research. Studies indicate that patients with low levels of zinc suffered from several symptoms, including a cell-mediated immune disorder, a characteristic of sickle cell disease. Zinc Deficiency Treatment Read more: http://www.livestrong.com/article/253219-the-benefits-of-zinc-sulfate/#ixzz1FydeZzMv Delineation of the protective action of zinc sulfate on ulcerative colitis in rats. Luk HH, Ko JK, Fung HS, Cho CH. Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 1/F, Li Shu Fan Building, 5 Sassoon Road, Hong Kong, PR China. The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats. Zinc sulfate at different concentrations was given either orally (p.o.) or rectally (p.r.) to rats at 42, 48, 66 and 72 h following the induction of colonic inflammation by DNBS. Rats were killed 96 h after instillation of DNBS rectally to assess the severity of colonic damage, myeloperoxidase and xanthine oxidase activities. The involvement of mast cell degranulation and histamine release in the pathogenesis of DNBS-induced colitis was determined by using a mast cell stabilizer (ketotifen) and histamine receptor blockers (terfenadine and ranitidine). DNBS given rectally produced inflammation and ulceration in rats with a pathology resembling ulcerative colitis. Myeloperoxidase activity but not xanthine oxidase activity was sharply increased by this agent. Intrarectal administration of zinc solution and parenteral injection of histamine blockers significantly reduced tissue damage and myeloperoxidase but not xanthine oxidase activity. Ketotifen, a mast cell stabilizer, also significantly decreased mucosal injury and 97 myeloperoxidase activity in the colon. In conclusion, mast cell degranulation followed by histamine release plays an important role in the pathogenesis of DNBS-induced ulcerative colitis. Zinc given rectally has a therapeutic effect against this colitis model, perhaps through the reduction of inflammation and inhibition of the above pathogenic mechanisms. PMID: 12044810 [PubMed - indexed for MEDLINE] Clinical double-blind trial of topical zinc sulfate for herpes labialis recidivans]. Kneist W, Hempel B, Borelli S. Klinik für Dermatologie und Allergie Davos, Alexanderhausklinik, Davos Platz, Schweiz. 1643B 164B 1645B 164B 1647B In a placebo controlled, double-blind clinical trial in patients with herpes labialis recidivans, zinc sulfate (CAS 7733-02-0) as gel (Virudermin Gel) proved to be significantly more effective than the gel alone. With zinc sulfate as gel, the symptoms were less marked and healing was faster. This simple preparation can be applied in cases of herpes labialis recidivans without any risk of side effects. Due to the antiseptic properties of zinc sulfate superinfections can be prevented. 98
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