Transcript Anthraquinones and glycosides

Anthraquinones and its glycosides
Pharmacognosy I
Mosul University/ College of Pharmacy
L.A. Dilbreen Barzanji
Anthraquinones and its glycosides
• Substances of the anthraquinone type were recognized
both in the free state and as glycosides.
• Natural products also contained reduced derivatives of
the anthraquinones (oxanthrones, anthranols and
anthrones) and compounds formed by the union of
two anthrones molecules (i.e dianthrones).
• Because glycosides are often easily hydrolysed, the
earlier workers tended to isolate products of hydrolysis
rather than the primary glycosides.
The following aglycones have long been established:
1. Crysophanol or crysophanic acid from rhubarb and
cascara.
2. Aloe-emodin from rhubarb and senna.
3. Rhein from rhubarb and senna.
4. Emodin or frangula-emodin from rhubarb and
cascara.
Improved extraction methods, developed by Stoll and his
colleagues, led to the isolation of main senna
glycosides, sinnosides A and B, in 1941. Since this date
many new glycosides including C-glycosides and
various stereoisomers have been isolated and their
structures determined.
Anthraquinones
• The derivatives of anthraquinone present in purgative drugs may be
dihydroxy phenols such as crysophanol, trihydroxy phenols such as
emodin or tetrahydroxy phenols such as carminic acid.
• Other groups are often present, for example, methyl in
crysophanol, hydroxyl-methyl in aloe-emodin or carboxyl in rhein
and carminic acid.
• Anthraquinones containing a free carboxylic acid group (e.g. rhein)
can be separated from other anthraquinones by extraction from an
organic solution with sodium bicarbonate solution.
• When such substances occur as glycosides, the sugar may be
attached to various positions.
• Anthraquinones derivatives are often orange-red compounds,
which may sometimes be observed in situ (e.g. in the medullary
rays of rhubarb and cascara).
Anthranols and anthrones
• These reduced anthraquinones derivative occur either
free or combined as glycosides. They are isomeric and
may be partially converted to the other in solution.
• The parent substance, anthrone is a pale yellow, nonflourescent substance which is insoluble in alkali; its
isomer anthanol, is brownish-yellow and forms a
strongly fluorescent solution in alkali.
Oxanthrones
• These are intermediate products between
anthraquinones and anthranols.
Dianthrones
• These are compounds derived from two
anthrone molecules, which may be identical
or different; they are readily formed as a
result of mild oxidation of the anthrone or
mixed anthrones (e.g. a solution in acetone
and presence of atmosprheric oxygen).
• Reidin A,B and C which occur in senna and
rhubarb are heterodianthrones, i.e. composed
of unlike anthrones.
Aloin-type or C-glycosides
• The aloin obtained from species of Aloe, although
one of the first glycoseides to be isolated, was a
problem for investigators for a long of time. It is
strongly resistant to normal acid hydrolysis but
may be oxidized with ferric chloride.
• A study of its degradation products indicated a
sugar-like chain and the structure shown, in
which the sugar is joined to the aglycone with a
direct C-C linkage (a C-glycoside).
• two aloins are known (A and B).
Senna leaf
• Senna (Sennae Folium) consist of the dried leaflets of
Cassia senna which are known in commerce as Alexandrian
or Khartoum senna.
• The senna plant is a small shrubs of the family
leguminosae, about 1 m high, with paripinnate compound
leaves.
• It may be grown either in dry lands or wetter conditions.
• Alexandrian senna is collected mainly in September, from
both wild and cultivated plants.
• The branches bearing leaves and pods are dried in the sun
and then conveyed to place where pods and large stalks are
separated by sieves, the leaves are then graded.
• Owing to the carefully way in which the drug is collected
and compressed into bales, few leaflets are usually broken.
• Constituents: aloe-emodin and rhein were first isolated
in 1913. Many compounds based on these two have
been obtained.
• Two active crystalline glycosides, sennoside A and
sennoside B. they both hydrolysed to give two
molecules of glucose and the aglycones sennidin A and
B. Sennidin A is dextrorotary and B is its mesoform.
• Sennosides C and D, which are the glycosides of
heterodianthrones involving rhein and aloe-emodin.
• It also contains other anthraquinone glycosides such as
palmidin A, etc.
• Evaluation: it is difficult to remove all fragments
of rachis, petiole and stalk from the drug, but the
amount of these structures is limited by BP to 3%.
• The BP/EP determines the total senna leaf
glycosides in terms of sennoside B (not less than
2.5%).
Senna fruit
• Senna pods (Sennae Fructus) are the dried ripe fruits of C.
senna .
• The pods are collected with the leaves and dried as
described above. After separation from the leaves they are
hand-picked into various qualities.
• The active constituents are located in the pericarp; they are
similar to those of the leaves, together with sennoside A,
which constitutes about 15% of sennoside mixture.
• Uses: the use of laxative is increasing and senna constitutes
a useful purgative for either habitual constipation or
occasional use. They lack astringent after-effect of rhubarb.
• Despite the availability of a number of synthetics,
sennoside preparations remain among the most important
pharmaceutical laxatives.
Cascara bark
• Cascara sagrada is the dried bark of Rhamnus purshianus.
• The bark is collected from wild trees which are 6-18 high,
growing in the pacific coast of North America.
• The bark is collected from mid-April to the end of August,
when it separate readily from the wood. Longitudinal
incisions about 5-10 cm apart are first made in the trunk
and the bark removed. The pieces are dried in the shade
with the cork uppermost.
• During preparation and storage the bark must be protected
from the rain and damp, or partial extraction of the
constituents may occur or the bark may be mouldy.
• That the bark must be kept for at least 1 year
before use is no longer a BP requirement but the
bark appears to increase in medicinal value and
price until it is about 4 years old.
• Many companies prefer to use bark which has
been stored for considerably more than 1 year
which are better tolerated but as effective as
those prepared from more recently collected
bark, this is presumably due to hydrolysis or
other changes during storage.
Cascara contains about 6-9% anthracene derivatives which are
present both as O- and C-glycosidic linkages. The following
groups are now manifest:
1. Four primary glycosides or cascarosides A,B,C and D, they
contain both O- and C-glycosidic linkages.
2. Two aloins, barbaloin derived from the aloe-emodin
anthrones and chrysaloin derived from crysophanol
anthrone. These C-glycosides are probably breakdown
products from (1).
3. A number of O-glycosides derived from emodin
oxanthrone, aloe-emodin and crysophanol.
4. Various dianthrones, including those of emodin, aloeemodin and crysaphanol and heterodianthrones palmidin
A, B and C.
5. Aloe-emodin, crysophanol and emodin in the free state.
• Uses: cascara is a purgative resembling senna
in its action. It is mainly used in the form of
liquid extract or elixir or as tablets prepared
from a dry extract. It is also used in veterinary
work.
Frangula bark
• Frangula bark, alder buckthorn, is obtained from
Rhamnus frangula (f. Rhamnaceae), a shrub 3-5 m high
and found in Britain and Europe.
• The bark included in the BP/EP is required to contain
not less than 7.0% glucofrangulins calculated as
glucofrangulin A.
• Frangula contains anthraquinone derivatives present
mainly in the form of glycosides. The rhamnoside
franguloside, or frangulin, consist of two isomers,
frangulosides A and B, formed by partical hydrolysis of
the corresponding rhamnoglycosides, glucofrangulins
A and B.
Rhubarb
• Rhubarb consists of the dried underground parts of Rheum
palmatum.
• The drug appears to obtained from both wild and cultivated
plants grown on the high plateau of Asia and Tibet to
south-east China.
• Chinese rhubarb has a long history. It is mentioned in
herbal of about 2700 BC.
• The BP/EP drug is required to contain not less than 2.2% of
hydroxyanthraquinone derivatives calculated as rhein.
• Collection and preparation: the rhizomes are grown at a
high altitude dug up in autumn or spring when about 6-10
years old, decorticated and dried.
Constituents:
Following type of anthraquinones in rhubarb:
1. anthraquinones without a carboxyl group (e.g.
crysophanol, aloe-emodin, emodin and physcion) also
their glycosides (crysophanein and glucoaloe-emodin).
2. Anthraquinones with a carboxyl group (e.g. rhein and its
glycoside, glucorhein).
3. Anthrones or dianthrones of crysophanol, or emodin or
aloe-emodin or physcion.
4. Heterodianthrones derived from two different anthrone
molecules. For example, palmidin A from aloe-emodin
anthrone and emodin anthrone.
Uses: rhubarb is used as a bitter stomachic and in the
treatment of diarrhea, purgation being followed by an
astringent effect. The drug is suitable as an occasional
aperients but not for the treatment of chronic constipation.
Aloes
• Aloe is the solid residue obtained by evaporating the
liquid which drains from the transversely cut leaves of
various species of Aloe (Liliaceae). The juice is usually
concentrated by boiling and solidifies on cooling.
• 180 known species of Aloe, the drug mainly obtained
from: A. ferox and A. Barbadensis.
• the genus Aloe includes herbs, shrubs and trees,
bearing spikes of white, yellow or red flower.
• Aloe leaves are fleshy, are strongly cuticularized and
usually prickly at the margins.
• Constituents: Aloe contain C-glycosides and resins. The
crystallines glycosides known as ‘aloin’.
• Aloin BP contain not less than 70% anhydrous
barbaloin.
• The main crystalline glycoside, barbaloin, is found in all
the commercial varieties.
• Barbaloin is a C-glycoside ; a 10-gluco-pyranosyl
derivative of aloe-emodin anthrone. Unlike Oglycosides, it is not hydrolysed by heating with dilute
acids or alkalis. However It can be decomposed
oxidative hydrolysis, with reagents such as ferric
chloride, when it yields glucose, aloe-emodin anthrone
and little aloe-emodin.
• Small quantities of aloe-emodin are sometimes present
in aloes, Cape aloe (A. Ferox) also contains aloinosides
A and B, which are O-glycosides of barbaloin.
• As with other anthraquinone producing plants, in
Aloe species the content of anthraquinones is
subject to seasonal variation. Anthraquinone
derivatives are confined to the leaf juices and
that aloin reaches a maximum concentration in
the dried leaf juices in the summer and lowest in
the winter.
• Uses: aloes is employed as purgative.
‘Aloe vera’ products
• Aloe vera products are derived from the mucilage
located in parenchymatous cells of aloe vera leaf and
should not be confused with aloes (which originate
from the aloetic juice of the pericyclic region).
• The mucilaginous gel has been used from early times
for the treatment of numerous conditions but in recent
years its use in herbal and cosmetic industries has
become very big business in the USA, Europe and
elsewhere.
• There are doubts about the true usefulness of the
products which feature as suntan lotions, tonics and
food additives.
Research over the last ten years has , however, largely upheld
a number of the therapeutic properties ascribed to the gel.
These include the anti-inflammatory properties (wound
healing, burn healing, frost bite), gastrointestinal activity
(peptic ulcer), antidiabetic activity, antifungal activity,
antibacterial activity and radiobiological protection. Not all
these properties have been unequivocally accepted.
The complex chemistry of the gel makes the attribution of the
various activities to specific compounds difficult.
Indeed beneficial clinical results for a particular condition may
arise from more than one component. Thus wound-healing
benefits may derive from the anti-inflammatory, fibroblaststimulating, antibacterial and hydrophilic properties of the
gel.
Hypericum- St. John’s wort
• Hypericum consists of the dried aerial parts of
Hypericum perforatum, gathered usually at the
time of flowering or shortly before. Commercial
extracts are standardized on their
naphthodianthrone content, expressed as
hypericin.
• Care should be taken during collecting as contact
photosensitivity has been reported. Drying at 700
for 10 hours is recommended.
Hypericum contains a variety of constituents with biological activity:
1. Anthraquinones: principally hypericin and pseudohypericin, also
isohypericin and emodin-anthrone.
2. The BP/EP requires not less than 0.08% of total hypericin.
3. Prenylated phloroglucinol derivatives: hyperforin (2.0-4.5%),
adhyperforin and furohyperforin.
4. These phloroglucinols constitute the principal components of the
lipophilic extract of the plant and considered to be the most
important active constituents regarding antibiotic and
antidepressant properties. Unfortunately they are very prone to
oxidative transformations and a number of such degradation
products have been identified.
5. Flavonoids
6. Volatile oils
7. Other constituents
• Action and uses:
• An explosion in the popularity of St. John’s wort related to
its unregulated availability for the treatment of mild to
moderate depression. In the USA,for the first eight months
of 1999, it ranked second to ginkgo as the best-selling
product of herbal mainstream market with retail sales
valued at over 78 million dollars. In Germany, it
represented 25% of all antidepressant presicriptions. It was
described as ‘nature’s Prozac’, without the disadvantegeuos
side-effects of the latter.
• However, a cautionary warning was struck. St John’s wort
will adversely affect the performance of a number of a
common drugs by causing their rapid elimination from the
body, either by enhanced metabolism or as a result of
increased action of the drug transporter P-glycoprotien.
Among common drugs so affected are anticoagulants sucha
s warfarin, digoxin, tricyclic antidepressant agents,
simvastatin and others.
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