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Anthraquinone Glycosides
Introduction to Anthraquinones

Historically: Rhubarb, Senna, Aloes and
Cascara were all used as purgative drugs.

Monocotyledons: Only Liliaceae.


Most commonly C-glycoside: barbaloin.
Dicotyledons: Rubiaceae, Leguminosae,
Polygonaceae, Rhamnaceae, Ericaceae,
Euphorbiaceae, Lythraceae, Saxifragaceae,
Scrophulariaceae and Verbenacacea. Also in
certain fungi and lichen.

Reduced derivatives of anthraquinones


Compounds formed by the union of 2
anthrone molecules


Oxanthrones, anthranols and anthrones
Dianthrones
Aglycones:
Chrysophanol/Chrysophanic acid  Rhubarb
and Senna.
 Rhein  Rhubarb and Senna
 Aloe-emodin  Rhubarb and Senna
 Emodin  Rhubarb and Cascara

Anthraquinones –
Chemical Properties

Anthraquinone derivatives: orange-red
compounds
Soluble in hot water/dilute alcohol.

Identified via Borntrager’s test






Powdered drug – macerated with ether
Filter
Add ammonia/caustic
Shake  pink, red or violet colour – positive for
anthraquinone derivatives
If the Anthraquinones are reduced (within the herb) or
stable (glycosides) test will be negative
Anthraquinone Structure
Anthranonls and Anthrones



Reduced anthraquinone derivatives
Occur either freely (aglycones) or as glycosides.
Isomers

Anthrone: Parent structure (pale yellow, nonsoluble in alkali, non-fluorescent)

Anthronol: brown-yellow, soluble in alkali,
strongly fluorescent

Anthronol derivatives (e.g. in Aloe – have similar
properties – fluorescence used for identification)
Oxanthrones

Found in Cascara bark
Intermediate products (between anthraquinones
and anthranols)

When oxidised  form anthraquinones

Accomplished via Modified Borntrager’s Test
(oxanthrones oxidised using hydrogen
peroxide)

Dianthrones




Derived from 2
anthrone molecules
2 molecules may/not
be identical
Form easily due to
mild oxidation of
anthrones
Form important
aglycones



Cassia
Rheum
Rhamnus
Senna - Leguminosae

Definition: Consists
of the dried leaflets of
Cassia senna
(Alexandrian senna),
or Cassia angustifolia
(Tinnevelly senna).
Cassia spp - Senna




Indigenous to Africa
(tropical regions)
Used since 9th – 10th
century
Introduced into
medicine by Arab
physicians (used both
the leaves and pods)
Exported by
Alexandria – name of
the Sudanese drug.
Senna - Collection





Collected in
September
Whole branches
bearing leaves are
dried in the sun.
Pods and large stalks
are separated with
sieves.
Leaves are graded
(whole leaves, whole
leaves and half-leave
mix, siftings).
Whole leaves – sold
to public

Rest – used for
galenicals.
Senna - Constituents

2 active glycosides:

Sennoside A
Sennoside B
Both hydrolyse: 2 molecules glucose +
aglycones: Sennidin A and Sennidin B.
Sennoside C & Sennoside D
 Rhein
 Aloe-emodin
 Palmidin A (Rhubarb)

Senna - Constituents

Kaempferol (yellow
flavanol)
+ glucoside
(kaempferin)

Mucilage
Calcium oxalates
Resin


Comparison of
Alexandrian and Tinnevelly Senna

Macroscopical






Macroscopical
Seldom larger than 4
cm in length
Grey-green
Asymmetric at base

Broken and curled at
edges
Few press markings




Seldom exceeds 5cm
in length
Yellow-green
Less asymmetric at
base
Seldom broken and
normally flat
Often shows
impressions (mid vein)
Comparison between
Alexandrian and Tinnevelly Senna

Microscopical


Hairs – numerous
(approximately 3
epidermal cells apart)
Most stomata have 2
subsidiary cells

Microscopical


Hairs less numerous
(approximately 6
epidermal cells apart)
Stomata have 2-3
subsidiary cells with
the respective ratio 7:3
Comparison between
Alexandrian and Tinnevelly Senna

Chemical Tests

Ether extract of
hydrolysed acid
solution of herb with
methanolic
magnesioum acetate
solution gives

Chemical Tests

Same Test

Pink colour in daylight


Pale green-orange
colour in filtered UV
light

Orange colour in
daylight
Yellow-green colour in
filtered UV light
Comparison between Alexandrian
and Tinnevelly Senna

TLC

Hydroxymusizin
glycoside present

TLC

Tinnevellin glycoside
present
Senna – Allied Drugs & Substitutes


Bombay, Mecca and
Arabian Sennas (found in
Cassia angustifolia from
Arabia).
Dog senna – Cassia
obovata

Cassia auriculata –
Indian Senna

Cassia podocarpa

Substitutes or
Adulterants

Argel leaves –
Solenostemma argel

Coriario myrtifolia
Senna Fruit

Definition: Senna
pods are the dried,
ripe fruits of Cassia
senna and Cassia
angustifolia, which
are commercially
known as Alexandrian
and Tinnevelly senna
pods respectively.
Both have separate
monographs
Senna Fruit - Collection

Pods are collected
with the leaves and
dried in a similar
fashion. After
separation of the
leaves, the pods are
hand-picked into
various qualities, the
finer being sold
(commercially), while
the finer pieces are
used to make
galenicals.
Senna Fruit - Constituents

Active constituents –
found in the pericarp

Similar to those
actives of the leaves


Sennoside A
Sennidin
Senna - Uses
Laxatives (habitual constipation or
occasional use).
 Lacks astringent after-effect (Rhubarb)

Senna - Additional




Medicinal Actions
Vermifuge, diuretic, febrifuge
Other uses: laxative candy
(bitter taste).



Also used to treat flatulence,
gout, fever.

Gout, colitis, GI inflammation.

Should not be used with
cardiac glycosides.

Seeds/pods give gentler action
than leaves: more appropriate
for the young, elderly and
those prone to stomach
cramps.

NB: Over-use causes
dependency.
Overdose: nausea, bloody
diarrhoea, vomiting and
nephritis.
Long-term use: dehydration &
electrolyte depletion,
worsening constipation and
weakening intestinal muscles.
Topically: poultice prepared
with vinegar to treat pimples.
NOTE: Senna may cause
urine to become reddish – no
clinical significance.
Contra-indications


Cascara Bark- Rhamnaceae

Definition: Official
cascara sagrada is
the dried bark of
Rhamnus purshianus.
Bark is collected from
wild trees
(depletion is leading
to the increase of
cultivation)
Rhamnus purhsianus - Cascara

Etymology


Rhamnos – Greek, branch,
shiny shrub. Purshiana
after Pursh, botanist 1st
described herb in 1814.
Other Common Names

Bearwood, bitterbark,
buckthorn, coffeeberry,
mountain cranberry,
persiana, sacred bark.
Cascara Bark - History



Recently introduced
to Modern Medicine.
Known to early
Mexican and Spanish
priests.
Not introduced to
medicine until 1877.
Cascara – Collection & Preparation

Collected form mid-April to end of
August, when it separates readily
from the rest of the trunk.

Longitudinal incisions are made
10cm apart and the bark removed.

Tree is then usually felled and the
branch bark separated.

Bark is then dried in the shade
with the cork facing upwards. This
is referred to as ‘natural’ cascara.
Commercial supplies are
comminuted to give small, even
fragments called ‘evenized’,
‘processed’, or ‘compact’ cascara.
Cascara Bark - Storage

During preparation and storage the bark should
be protected from rain and damp (partial
extraction of constituents may occur or bark may
become mouldy).

Should be stored for at least 1 year before use
(although no longer a BP requirement).

Bark appears to increase in medicinal value up
unto its 4 years old (stored bark)
Cascara Bark – Why Stored for a
Year?



When stored for at least a
year – better tolerated by
patient (less griping pains
due to increased
peristalsis)
Yet as effective as fresh
bark.
Reason?

Due to Hydrolysis and
other changes that occur
during storage.

Bitter taste of Cascara can
also be reduced by treating
the bark with alkali (alkali
Cascara Bark – Constituents 1

4 main glycosides – Called Cascarosides
Cascaroside A
 Cascaroside B
 Cascaroside C
 Cascaroside D

Cascara Bark – Constituents 2

2 aloins:
C – Glycosides
 Breakdown products of Cascarosides A-D

 Barbaloin
(derived from aloe-emodin)
 Chrysaloin (derived from chrysopanol anthrone)
Cascara Bark – Constituents 3
O-glycosides
 Derived from

Emodin
 Emodin oxanthrone
 Aloe emodin
 chrysophanol

Cascara Bark – Constituents 4

Dianthrones
Those from
 Emodin
 Aloe-emodin
 Chrysophanol


Hetrodianthrones
 Palmidin
A, B and C (Rhubarb)
Cascara Bark – Constituents 5
Emodin
 Aloe-emodin
 Chrysophanol

(in the free state)
Cascara Bark - Substitutes

Rhamnus alnifolia (too rare)

Rhamnus crocea (bark is very different from
official drug)

Rhamnus californica (so closely related to
Rhamnus purshianus some botanists do not
consider them to be separate species).

Rhamnus fallax
Cascara Bark - Uses
Purgative
 Similar to Senna
 Normally as a tablet
 Also used on animals

Cascara Bark – Additional

Physiological Action

Excessive use: nausea,
vomiting, heamatorrhoea.
Long term use: Weakens
intestinal muscles.

Contra-indications:
children younger than 14,
during pregnancy,
lactation, IBS, Crohn’s,
intestinal obstruction, and
idiopathic abdominal
pain.
Astringent (bark – tannins),
bitter tonic, chologogue,
emetic, hepatic, stomachic.
Medicinal Uses
Move stagnation, clear heat.
The most widely used laxative
world-wide.
Topically: Used as a wash for
herpes lesions


Rhubarb - Polygonaceae

Definition:
Rhubarb/Chinese
Rhubarb is the
rhizome of Rheum
palmatum. Other
species and hybrids
of Rheum, except R.
rhaponticum, may
also be included.
Chinese Rhubarb - History




Chinese Rhubarb has
a long history.
Mentioned in a herbal
of 2700BC.
Formed an important
article of commerce
on the Chinese trade
routes to Europe.
Still used medicinally
today.
Chinese Rhubarb – Collection &
Preparation






Rhizomes are grown at
high altitudes (+3000m).
Collected in Autumn or
spring (6-10yrs old)
Cork is removed, cut.
Artificially dried.
Packed in tin-lined
wooden cases.
Inferior quality herbs are
packed in hessian bags
Chinese Rhubarb - Constituents
1.
Anthraquinones without
a carboxyl group –
chrysophanol, emodin,
aloe-emodin &
physcion.
Also the glycosides of
these substances.
2. Anthraquinones with a
carboxyl group (rhein
and its glycoside:
glucorhein).
Chinese Rhubarb - Constituents
3.
Anthrones and
dianthrones of
chrysophanol,
emodin, aloeemodin or physcoin.
4. Dianthrone
glucosides of rhein
(Sennosides A and
B).
5. Hetrodianthrones
derived from 2
different anthrone
molecules: Palmidin
A and Palmidin B.
Chinese Rhubarb - Constituents

Free anthraquinones:
chrysophanol,
emodin, aloe-emodin
and rhein.

Some of the above
constituents may also
occur as glycosides.
Chinese Rhubarb - Uses
•
•
•
•
Bitter stomachic
Diarrhoea (low doses)
– contains tannins
Purgative (high
doses) – followed by
an astringent effect.
Suitable only for
occasional for
occasional use, not
for chronic
constipation.
Rhubarb - Additional

Etymology



Rheo – Greek, ‘to flow’, in
reference to the purgative
properties.
Topical Uses:

Medicinal Actions

Anti-helminthic, antibacterial, anti-inflammatory,
antiseptic, astringent (low
doses), sialagoge,
vulnerary
Poultice to treat boils,
burns, wounds. Used to
stop bleeding (tannins –
stypic and astringent).
Used as a mouthwash for
oral ulcers.

Other uses: Acid content:
fresh root can be used to
polish brass.

Caution

Leaves should be avoided
– high calcium oxalate toxic
Aloe - Liliaceae
Definition: Aloes are the
solid residue obtained by
evaporating the liquid
which drains from the
transversely cut leaves of
various Aloe species.
The juice is usually
concentrated by boiling
and solidifies on cooling.


Official varieties are the
Cape Aloes from SA and
Kenya (Aloe ferox), and
the Curacao Aloes from
West Indies (Aloe
barbadensis).
Preparation of Cape Aloes
Cape Aloes are prepared from the wild plants of Aloe ferox.
Leaves are cut transversely near the base.
200 leaves arranged around a shallow hole in the ground
(lined with canvas or goatskin).
Cut ends overlap & drain into the canvas.
After 6hrs all the juice is collected.
Transferred to a drum.
Boiled for 4hrs on an open fire.
Preparation of Cape Aloes
Cape Aloes - Characteristics

Dark brown or Greenbrown

Glassy masses

Thin fragments have
a deep olive colour

Semi-transparent.
Cape Aloes - Characteristics

Powder: green-yellow

Rub 2 pieces of drug
together – powder is
found on the surfaces.

Characteristic sour odour
(rhubarb/apple-tart
odour).

Taste: nauseous and
bitter.

Microscopy: powder in
lactophenol – amorphous.
Characteristics of Curacao Aloes









Colour: yellow-brown –
chocolate brown.
Poor qualities
(overheated) black colour.
Opaque
Breaks with a waxy
facture
Semi-transparent
More opaque on keeping.
Nauseous and bitter
taste.
Characteristic iodoform
odour.
Microscopy: lactophenol
– acicular crystals
Aloes - Constituents



C-glycosides
Resins
Glycosides

Aloin



Barbaloin
Isobarbaloin
Aloe-emodin
Cape Aloes: Also Contain
Aloinoside A & Aloinoside B
(O-glycosides of
barbaloin)
Aloe - Constituents
Aloe Constituents & Chemical
Tests:
Unlike C-glycosides, O-glycosides of
Aloe are not hydrolysed by heating
with dilute acids or alkali.
 Can be decomposed with ferric
chloride & dilute HLC - NB:
Modified Borntrager’s Test –
oxidative hydrolysis.
Anthraquinones give a red colour
when shaken with dilute ammonia.

NB: All Aloes give a strong green
fluorescence with borax
(characteristic of anthranols) General test for aloes.
Aloe - Uses

Purgative

Seldom prescribed alone
– activity is increased
when administered with
small quantities of soap
or alkaline salts;
Carminatives moderate
griping tendency.

Ingredient in Friar’s
Balsam.
Aloe – Additional Notes

Medicinal Uses:

Anti-bacterial, anti-fungal,
chologoge, emmenogogue,
anti-inflammatory (juice),
anti-inflammatory ,
demulcent, vulnerary,
immune-stimulating (gel).

Etymology


Other uses

Radiation burns (internal and
external use)


Contra-indications
Pregnancy & lactation
(internal uses)
Name derives from Arabic
alu, meaning shiny or bitter
in reference to the gel.
Khoi-San hunters rub gel
on their bodies to reduce
sweating and mask their
scent.
Used to break nail-biting
habit.
Aloe vera Products




These are derived from
the mucilage gel –
parenchyma cells
Should not be confused
with aloes (juice of
pericycle – juice used for
laxative effect).
Cosmetic industry
(usefulness often
exaggerated) - Used as
suntan lotions, tonics and
food additives.
Mucilage =
polysaccharide of
glucomannans and pectin
Cochineal


Definition: Cochineal
is the dried female
insect, Dactylopius
coccus, containing
eggs and larvae.
Insects are
indigenous to Central
America, commercial
supplies are derived
from Peru.

Eggs are protected during
the rainy season are
‘sown’ on cacti – on
which it is intended to
breed.

Both male and females
arise. After a time,
fecundation occurs.
Females attach
themselves to the cacti
and the males die out.

Females swell to x2 their
original size due to
developing larvae &
develop red colouring
matter.
Cochineal
Cochineal

Larvae mature after 14days and escape from
the now dead body of the parent.

Only a small portion develop into males.

For next 2 weeks, males fly and young females
crawl on the plant.

Life cycle = 6 weeks.

3-5 generations may be produced in 1 season.
Cochineal - Collection






Insects are brushed from plants with small
brooms and killed (some left to provide for
subsequent crops).
First crop killed contains the most colouring
matter.
Insects are killed by plunging them in boiling
water, stove heat or exposure to fumes by
burning sulphur or charcoal.
If heat is used – insects change to purple – black
– called ‘black grain’.
Fume killed – turn purple-grey called ‘silver
grain’.
Small immature insects and larvae which can be
separated by sieves are sold as ‘granilla’ or
siftings.
Cochineal Collection
Cochineal - Characteristics
Oval in shape
Half cm in length
Examined
microscopically after
removing the
colouring matter
(ammonia solution).
Each insect contains 60
– 450 eggs and
larvae.
Cochineal - Constituents






C-glycoside – anthraquinone derivative  bright
purple, water-soluble colouring matter
Carminic acid
Fat
Wax
Adulteration: occurs by increasing the weight of
the insects by ‘dressing’ it with inorganic matter
in a colour which blends in with that of the
insect.
Detected when insects are placed in water
Last Word on Anthraquinones

Anthraquinones take about
10hours to produce an effect
(take overnight)

Should not be used for more
than 10 days.

Should not be used by
children, pregnant and
lactating women.

Cause griping pain.

Are habit-forming.

Anthraquinones = phenolic
glycosides, used as an
irritating laxative