LOGO Herbal Medicine in Endocrinology and Metabolic Disease CONTENTS Introduction Presented by Lee Mina Gout October 22 2007 Obesity College of Pharmacy, Seoul National University LOGO Hyperlipidemia Thyroid Disorder Menopause Toxicity Conclusion Introduction Target of Study LOGO Gout – Primary problem Herbal options in treating metabolic and endocrine disease Not, excessive intake of purine –containing food Diabetes Mellitus and Gout – wide range of natural treatment Heart disease → cholesterol-lowering plant → no tradition of usage Obesity → Increasing problem But, enzyme defect in urate metabolism →buildup of uric acid →when it crystallizes in joint, acute inflammation ; Gout Simple solution is the most important challenge in treating metabolic disease and herbal options are being explored No uricase in human Uric acid Side effect of hormone replacement therapy during menopause → traditional plant therapy However, long-term plant usage may also be associated with side effects uricase allantoin CONTENTS Diabetes Mellitus 2 / 37 Study of Gout LOGO Prevalence of Gout ▪ ▪ ▪ ▪ Study of Gout LOGO Gout → 3~5 people /100 The frequency increases with age More than 1% of the over-30 population are troubled with attacks Many traditional remedies are found in different parts of the world Figure 1 Prevalence of gout in US men, 1990−1999 (adapted, with permission, from Wallace et al. 2004)3 Treatment of Gout Study of gout LOGO Culpepper ▪ listed more than 40 different herbal treatments, 4C ago Figure 2 Prevalence of gout in men in New Zealand Treatment ▪ plants → mild diuretics ( remove excess water) ▪ theory → toxic substance(uric acid) remove through the kidney But, orthodox diuretics therapy and removal of fluid ▪ in fact, uric acid↑ → gout ↑ Mild diuretics ▪ Dandelion (Taraxacum officinale) ▪ Celery (Apium graveolens) ▪ Parsley (Petroselinium crispum) ▪ Nettle (Urtica dioica) ▪ Carrot (Daucus carota) Roddy E et al. (2007) The changing epidemiology of gout Nat Clin Pract Rheumatol 3: 443–449 doi:10.1038/ncprheum0556 Roddy E et al. (2007) The changing epidemiology of gout Nat Clin Pract Rheumatol 3: 443–449 doi:10.1038/ncprheum0556 LOGO Gout – Orthodox medicine Study of gout Xanthine oxidase inhibitor Allopurinol Interfere with purine metabolism stop the buildup of uric aicd Indomethacin Medicine No reliable clinical study NSAIDS in Gout NSAIDS except aspirin,salicylate Probenecid Uricosuric Agents Sulfinpyrazone Gout – Orthodox medicine Study of gout LOGO Gout – plant threapy Study of gout LOGO In nature, some fruits → weak xathine-oxidase-inhibitoring property Gout Study of gout LOGO Colchicine ▪ The most rapidly effective conventional treatment for acute attack. ▪ Alkaloid, first isolate from the meadow saffron (Colchicum autumnale) Flavonoid content ▪ Prevent tublin polymerization into microtubules ▪ Chiso (Perilla frutescens) preventative treatment ▪ Skullcap (Scutellaria baicalensis) ▪ Yarrow (Achillea millefolium) ▪ Suppress the release of inflammation-causing chemicals from WBC ▪ Inhibit the formation of leukotriene B4 ▪ But, GI side effect↑ colchicine Cyanidin content ▪ therapeutic option Gout weed (Aegopodium podagraria) ▪ traditional European treatment ▪ but, no effect red yarrow → eating half a pound of cherries per day cherry Gout Study of gout LOGO Plant (natural aspirin-like substance) Willowbark (Salix alba) Meadowsweet (Spirea ulmaria) Poplar (Populus spp.) Turmeric (Curcuma longa) Boswellia (Boswellia serata) Ginger (Zingiber officinale) Black cohosh (Cicimifuga racemosa) Study of DM LOGO Prevalence of Diabetes Mellitus ▪ treat inflamed joints ▪ their effect is much slower than orthodox therapy 1. 2. 3. 4. 5. 6. 7. Prevalence of Diabetes Mellitus Component ▪ Bromelain ▪ Boswellia serata ▪ With the increasing age and obesity, an epidemic of non-insulin-requiring diabetes is developing ▪ in western population 2/3male, 1/3 female – overweight ▪ 100million diabetics worldwide, expected to grow 350million by 2025 ▪ about half of these people →without orthodox medicine Herbal alternative are widely used ▪ Turmeric root Devil`s claw(Harpagophytum procumbens) ▪ analgesic effect ▪ little anti-inflammatory potential No clinical trials have adequately demonstrated the effectiveness of these Age Residence Physical activity Ethnicity Obesity Study of DM LOGO World wide epidemic Diabetes Mellitus Study of DM LOGO Prevalence of India ▪ In the indian subcontinent, genetic factors → high incidence of diabetes ▪ many traditional ayurvedic medicines are used ▪ Plant metabolism is based on carbohydrates Sugar-lowering potential of plants 1. Madagascar periwinkle (Catharanthus roseus) 2. Bitter gourd (Mormordica charantia) No satisfactory clinical study 3. Fenugreek (Trigonella feonumgraecum) India: 2000:32 mill 2020: 81 mill 4. Jambul (Sygyium cumini) 5. Gymnema (Gymnema sylvestre) Extensive animal study No good human study Madagascar periwinkle (Catharanthus roseus) Zimmet, Nature 2001 Diabetes mellitus – Orthodox medicine Study of DM LOGO Study of DM LOGO Diabetes mellitus Table 18.1 herbal plants and diabetes proposed mode of action Biguanide Metformin ▪ most useful medication for treating diabetes in the obese ▪ developed from a commmonly used herbal remedy → goat`s rue (Galega officinale) Reduce/slow sugar absorption ▪ makes insulin more effective Stimulate Insulin production Stimulate Liver function both liver and muscle receptor ▪ cause weight loss ▪ used in the 1500s to treat the plague ▪ found to lower blood sugar in 1927 ▪ carried out extensive research in the 1930s to produce a synthetic compound Title Unknown ▪ Aloe Aloe vera ▪ Guar goat`s rue (Galega officinale) Reduce Insulin resistance Cyamopsis tetragonoloba ▪ Wild oats Avena sativa ▪ Barley Hordeum disticum ▪ Indianipecac Gymnena sylvestre ▪ Fenugreek Trigonella foenum-graecum ▪ Chicory ▪ Periwinkle Cichorium intybus ▪ Ginseng Panax ginseng ▪ goat`s rue Catharnthus roseus Galega officinale ▪ Chinese -foxglove Rehmannia glutinosa Diabetes Mellitus Target of Study LOGO Plant – containing high levels of Chromium Target of Study LOGO Diabetes is another condition in which antioxidants have been suggested beneficial, US Physician Study showed no reduction in incidence of Type II DM With long term B-carotene supplementation ▪ reduce insulin resistance ▪ Human study → lipid lowering ▪ Animal study → hypertension ◎ Barley (Hordeum disticum) ▪ slow sugar absorption ▪ high Cr → lowering blood sugar in rat Other herbs Sulphur-containing herbs ◎ garlic (Allium sativum), onion → insulin ↑ Improve liver function & hepatic glucose utilization in the liver ◎ chicory (Cichorium intybus) ginseng (Panax ginseng) → effective hypoglyceimic agent Diabetes Mellitus Diabetes Mellitus Study of DM LOGO More than 1200 hypoglycemic plant (Half traditional and half experimental evidence) → future treatment Herbal treatment of diabetic complication ◎ Evening primrose (Oenothera biennis) ◎ Baical skullcap (Scutellaria baicalensis) → treat diabetic complication involving the nerve and eye → reduce toxic metabolite buildup in nerves by aldose reductase inhibition ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪ carrot Nettle Dandelion Sunflower (Helianthus annuus) Life root (Senecio neurorensis) Bilberry (Vaccinium myrtillus) St. Mary`s thistle (Silybum marianum) Licorice (Glycyrrhiza glabra) Andrographis (Andrographis paniculata) Introduction of Overweight and Obesity What are Overweight and Obesity? LOGO Overweight and Obesity ▪ Abnormal or excessive fat accumulation that may impair health Body mass index (BMI) ▪ A simple index of weight-for-height that is commonly used in classifying overweight and obesity ▪ The same for both sexes and for all ages of adults ◎ BMI (kg/m2) = Weight / (Height)2 = 52/1.632 = 19.57 kg/m2 ◎Topical cayenne (Capsicum) → reduce pain in diabetic peripheral neuropathy Extensive overview by Ernst in 1997 → lack of adequate studies of hypoglycemic plant remedies makes their use difficult to support Classification BMI (kg/m2) Principal cut-off point Underweight <18.50 Obese Normal range Overweight class I class II 18.50 - 25.00- 30.00 - 35.00 - 24.99 29.99 34.99 39.99 class III ≥40.00 3 / 37 Introduction of Overweight and Obesity Facts about Overweight and Obesity LOGO Country comparison - BMI Obese Adults (%), Most recent Introduction of Overweight and Obesity LOGO Overweight and Obesity are a major risk factor for chronic diseases USA 32.2 U.K. 24.2 Germany Musculoskeletal disorders – arthritis of spine & legs Cardiovascular disease 19.4 Australia 16.4 Canada 15.3 Japan Korea Heath Consequences of Overweight and Obesity 3.1 2.4 Overweight Diabetes Hypertension & Obesity BMI Overweight and Obese Adults in the world (million), by 2015 Obesity 1600 2005 Over weight 2300 2015 Breathing difficulty - Sleep apnea Cancers 400 2005 2015 700 Reported by 4 / 37 What causes obesity and overweight? Introduction of Overweight and Obesity LOGO The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and expended 5 / 37 Targets of Anti-Obesity Treatment Neurobiological mechanism Tendencies of ethnic groups Living habits Overweight & Obesity Poverty link Additional factors LOGO Orthodox medicine → short-term treatments Targets Management of obesity → restrict calorie intake → ”wonder cures” Overeating Introduction of Overweight and Obesity Mode of action CNS adrenergic stimulants Reducing food intake Increasing energy expenditure Altering metabolism Regulation of hormone Selective serotonin reuptake inhibitor Adrenergic β3-agonist List of drugs Remarks and Side effect Bensphetamine (Ergoset,Bromidine) High chance of misuse Dietylpropion (Amfepramone,Tenuate) Primary pulmonary High chance of Hypertension Fenfluramine (Pondimin,Ponderal) Dexfenfluramine (Redux) Damage of valves of the heart Withdrawn an approval by FDA Fluoxetin (Prozac,Proctin) Disapproved by FDA Silbutramine (Meridia) Approved by FDA in ‘97 Ephedrine/caffeine combination BRL 26830, BRL 35135, CL 316243, RO 40-2148, RO 16-8714, ZD 7114 Lipase inhibitor Orlistat (Xenical) Fat substitutes Olestra Pseudoleptin, Neuropeptide Y restrainer Approved by FDA in ‘99 Introduction of Overweight and Obesity Targets of Anti-Obesity Treatment LOGO Domestic consumption drugs for reducing food intake and obesity Name of drugs Ingredient Green tea, orthosiphoris OTC Narmin Cap. Green tea, orthosiphoris OTC Diaen Cap. Green tea, orthosiphoris OTC Diva Cap. Green tea, orthosiphoris OTC Rosecana Cap Green tea, orthosiphoris OTC Reductil Cap. Sibutramine Prescription Maront Cap. Norpseudophedrine Prescription Exollise Cap. Green tea Xenical Cap. Orlistat Prescription Furimin Tab. Phendimetrazine tartate Prescription Freesel Cap. Calcium gluconate Free-L Cap. Arsobic acid , phenylpropanolamine Study of obesity LOGO Garcinia cambogia ▪ Hydroxy citric acid from Indian plant Class Greenphon Cap. Obesity ▪ it is incorporated into many weight-reducing products ▪ in vitro → beneficial effect on the fat metabolism, appetite suppression, weight reduction Garcinia Cambogia Extract (Citrimax) → 50% HCA - 500 mg ▪ in human → no benefit OTC Gymnema ▪ ayurvedic medicine, reducing appetite, losing weight OTC ⇒some animal experiments suggest benefit, no human studies have been conducted Prescription 8 / 37 Obesity Study of obesity LOGO Hyperlipidemia LOGO Study of hyperlipidemia Cholesterol →cause of disease in heart and circulation South African catus, Hoodia annilata ▪ used by the Kalahari bushman to suppress appetite No historical basis for lipid-lowering herbal therapy ▪ clinical trial as a weight loss aid ▪ Need closer scientific evaluation Orthodox treatment Non proven herbal remedy 1.Guarana (Paullinia cupana) – high caffeine Hoodia annilata ▪ a group of drugs called the statins ex)simvastatin, pravastatin → produced by fungi 2.Bladderwrack (Fucus vesiculosus) – high iodine 3.Chili (Capsicum annuum) 4.Mahuang (Ephedra sinica) – ephedrine Side effect ▪ nervous system, cardiovascular system, psychosis, seizure, strokes, heart attacks lovastatin simvastatin Hyperlipidemia Study of LOGO hyperlipidemia Hyperlipidemia Study of LOGO Hyperlipidemia Psyllium (Plantago isphagula) Plant sitosterol, sitostanol ▪ small effect ▪ High-fiber diet → cholesterol absorption↓ ▪ reduce cholesterol absorption ▪ vegetarian ≫ omnivorous Soya bean (Glycine soja) Soy product Psyllium (Plantago isphagula) ▪ effective dietary remedy ▪ meta-analysis of 38 controlled clinical trials confirmed benefit ▪ soy – 1960s, first clinical study trial prior to lipid-lowering agents ▪ available in a variety of spreads ▪ regular use products significant improvement in the lipid profile ▪ recommended by the AHF Garlic acid Pine tree-derived sterol ▪ lowering cholesterol ▪ cardiovascular benefits → antiplatelet action → reducing blood viscosity → improving endothelial function ▪ controversy but, modest benefit on the meta-analysis ▪ Become available as additives to spread ▪ have confirmed low-density lipoprotein cholesterol-lowering property Hyperlipidemia Another approach ▪ walnut, olive oil, fish oil, evening primrose Study of LOGO Hyperlipidemia Thyroid disorder LOGO Study of Thyroid disorder Globe artichoke (Cynara scolymus) ▪ reduce hepatic cholesterol production Thyroid Overactivity (Thyrotoxicosis) Red clover (Trifolium pratense) Uncommon condition affecting mainly women ▪ treatment of menopausal symptom ▪ isoflavone (genistein, daidzein, biochamin A) polyphenol Red clover (Trifolium pratense) Thyroid disorder ▪ no cholesterol-lowering effect in post-menopausal women Thyroid Underactivity (Myxoedema) ▪ but, HDL↑ Common, particulary(2~3%) in older women, and is often undiagnosed Herbal remedy ▪ Rhubarb (Rheum palmatum) ▪ Turmeric (Curcuma longa) ▪ Devil’s claw (Harpagophytum procumbens) ▪ Gulgul (Commiphora mukul) Lipid-lowering potential But, no confirm in humans Click to add text Thyroid disorder - thyrotoxicosis LOGO Study of Thyroid disorder Thyroid Disorder – thyroid underactivity Bugleweed (Lycopus virginicus), Gypsy (Lycopus europaeus) Underactive thyroid gland ▪ European plants, traditional use ▪ treating palpitations, goiter (thyroid swelling), Grave`s disease ▪ Caused by Iodine deficiency LOGO Study of Thyroid disorder ▪ This can be corrected by increasing iodine intake ►Experimental work ▪ Addition of iodine to salt → option in iodine-deficient areas ▪ An effect on output of various pituitary hormone → TSH, gonadotropins, Prolactin ▪ kelp (Fucus vesiculosys) – iodine↑ ►Work in humans Natural therapy ▪ effect iodine metabolism and thyroxine hormone ▪ but, clinical effect – mild ▪ radish (Raphanus sativus) – Russian folk medicine ▪ walnuts (Juglans spp.) – Turkish folk medicine Lithospermum officinale, lemon balm (Melissa officinale) ▪ mustard (Brassica nigra) - Europe ►Laboratory work ▪ motherwort (Leonurus cardiaca) – supported by German Commission E - treat thyroid overactivity - controlling the resulting palpitations though its direct effect of the heart ▪ react with the antibody produced in thyrotoxicosis ▪ no clinical study Prevalence of Menopause Study of Menopause LOGO Many women suffer from menopausal symptoms in middle age ▪ 70% → estiamted to experience flushes ▪ 40% → mood swings Menopause Study of Menopause LOGO Plant estrogen ▪ fruits, vegetable, cereal ▪ soy diet : promoted as an alternative, but need large amounts ▪ benefit → treating high cholesterol, osteoporosis and →reducing the risk of cancers Side effects of Hormone Replacement Therapy (HRT) ↑ Side effect of high levels of phytoestrogens Natural alternatives are commonly used Scandinavian survey ▪ 21% → hormone replacement therapy ▪ 45% → alternative therapy ▪ eipdemiological evidence → adverse effect on male sexual development in pregnancy Menopause Study of Menopause LOGO Menopause Black cohosh (Cimicifuga racemosa) Ginseng, evening primrose oil, angelica ▪ used by Algonqium Indians of North America ▪ no proven benefit Target of Study LOGO to treat premenstrual problems ▪ approved by the GCE for premenstrual syndrome, dysmenorrhea, Menopausal symptoms ▪ safe and effective alternative to estrogen therapy Wild yam (Dioscorea villosa) ▪ alternative approach to hormone therapy ▪ but, no effect ▪ diosin (progesterone precursor – not convert in body) Conclusion LOGO Conclusion of Study ▪ Our diet has changed VS Our metabolism has not ▪ People are reluctant to change eating habits. ▪ Herbal supplement reduce the metabolic disorder. ▪ This change should not be based on laboratory experimentation, pseudoscience, testimonials. ▪ Until such time as medical benefit is proven in clinical trial, we should use orthodox treatment. ▪ In the long time, traditional plants therapies will be proven effective and incorporated into orthodox treatment regimes. A recent Australian study of a traditional Chinese formula containing 12 Herbs showed no symptom improvement over three months.
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