Khellin

The active principle in extracts of Ammi visnaga, an umbelliferous plant growing in the
Near East; used in angina pectoris and asthma.

 Chemical formula: C14 H12 O5

 Molecular mass: 260.24
 Form: hard/ compact
 Colour: Colourless or brightly yellow
 Odour: characteristic
 Solubility: In water hardly soluble; less soluble in EtOH and acetone; hardly
soluble in ether; slightly soluble CHCI3

Gymnema sylvestris
Classification:_
Kingdom : Plantae
Division : Angiospermae
Class : Dicotyledoneae
Order : Contortae
Family : Asclepiadaceae
Genus : Gymnema
Species : sylvestre R.Br
Botanical synonym:
Asclepias geminata Roxb.
Periploca sylvestris Retz
Part used: Leaves
(e) Botanical description : Large climbers, rooting at nodes, leaves elliptic, acuminate,
base acute to acuminate, glabrous above sparsely or densely tomentose beneath; Flowers
small, in axillary and lateral umbel like cymes, pedicels long; Calyx-lobes long, ovate,
obtuse, pubescent; Corolla pale yellow campanulate, valvate, corona single, with 5 fleshy
scales. Scales adnate to throat of corolla tube between lobes; Anther connective produced
into a membranous tip, pollinia 2, erect, carpels 2,unilocular; locules many ovuled;
Follicle long, fusiform.
(f) Geographical distribution : Through out India, in dry forests upto 600m, common
throughout the district from January to November. Distributed in Asia, Tropical Africa,
Malaysia and Srilanka.
(g) Traditional uses : Sushruta describes Gymnema sylvester, as a destroyer of
madhumeha (glycosuria) and other urinary disorders. On account of its property of
abolishing the taste of sugar it has been given the name of gur-mar meaning sugar
destroying and it is believed therefore that it might neutralize the excess of sugar present
in the body in Diabetes mellitus.
The plant is also reported to be bitter, astringent, acrid, thermogenic, anti-inflammatory,
anodyne,digestive, liver tonic emetic, diuretic, stomachic, stimulant, anthelmenthics,
laxative, cardiotonic, expectorant, antipyretic and uterine tonic. It is useful in dyspepsia,
constipation,jaundice, haemorrhoids, renal and vesical calculi, cardiopathy, asthma,
bronchitis, amenorrhoea, conjuctivitis and leucoderma.
Active Constituents
Plant constituents include two resins (one soluble in alcohol), six-percent gymnemic
acids, saponins, stigmasterol, quercitol, and the amino acid derivatives betaine, choline,
and trimethylamine.
Antidiabetic activity :
Gymnema sylvestre a plant used in the Ayurvedic medicine of India for the treatment of
Diabetes
mellitus has been known from antiquity also to have an antisaccharin taste effect. The
active principles are glycosides (several Gymnemic acid) which shows selective
anaesthetic effect.
In a study conducted on rats the feeding of powdered leaves of Gymnema sylvestris in the
diet for 10 days prior and 15 days after the treatment of beryllium nitrate significantly
protected the animals from the full fall of blood glucose seen in rats receiving beryllium
nitrate alone. The feeding of the leaves for 25 days to normal rats did not alter blood
glucose significantly. The exact mode of protective action against beryllium toxicity was
not established.
Experimental studies were conducted on rats fed on high carbohydrate diet for 15 days
and later
rendered hyperglycaemic by injecting anterior pituitary extract 100mg/kg subcutaneously
daily for ten days. These animals were treated with ethanol extract of Gymnema sylvestre
at a dosage of 100mg/kg orally. Results indicated insignificant reduction in blood sugar
in normal rats, whereas significant reduction in anterior pituitary treated hyperglycaemic
rats. Effect of the drug was comparable to that of tolbutamide (50mg/kg) in the
hyperglycaemic rats. The drug influenced the disturbed carbohydrate metabolism in
hyperglycaemic animals by limiting the carbohydrate turnover and thus inhibiting the
vicious cycle of hyperglycaemia.
Further studies were conducted on albino rats to establish the antidiabetic activity of
Gymnema
sylvestre, which was compared with other conventional indigenous oral antidiabetic
drugs like Coccinia indica, Pterocarpus marsupium, Momordia charantia. The animals
were subcutaneously injected with 100mg/kg dose of the anterior pituitary extract, these
animals were then fed with alcoholic extract of Gymnema sylvestre and Coccinia indica
(100mg/kg each), aqueous infusion of Pterocarpus marsupium (20ml/kg), extract of
Momordia charantia (5ml/kg) and tolbutamide (50mg/kg) orally. Inhibition of the
hyperglycaemic response of the anterior pituitary extract at 6, 12 and 24 hours was most
marked in tolbutamide & Gymnema sylvestre. The inhibitory effect was highly significant
in Gymnema sylvestre when compared with Pterocarpus marsupium and Momordia
charantia.
The usefulness of Gymnema sylvestre therapy in alloxan induced diabetic rabbits in
correcting the abnormal accumulation of lipids, glycogen and protein depletion in the
liver, kidney and muscle were investigated by feeding crude leaf powder at a dosage of
250mg/kg body weight once a day.
Gymnema sylvestre therapy not only produced blood glucose homeostasis but also
increased the
activities of the enzymes affording the utilization of glucose by insulin dependent
pathways, it controlled phosphorylase levels, gluconeogenic enzymes and sorbitol
dehydrogenase. The uptake and incorporation of glucose into the glycogen and protein
are increased in the liver, kidney and muscle in Gymnema sylvestre administered diabetic
animal when compared to the untreated diabetic animals.
The inhibitory effects of an extract of Gymnema sylvestre and purified gymnemic acid on
Gastic
Inhibitory Peptide (GIP) release was studied in rats. The GIP release into the portal vein
in response to duodenal infusion of D-glucose in presence of leaf extract of Gymnema
sylvestre at a dosage of 0.5ml/kg. The results suggested that a glucose receptor which
interacted with the leaf extracts of Gymnema sylvestre and purified Gymnemic acid. The
inhibition of GIP release by Gymnemic acid observed was attributed to the interaction
with the glucose receptor for GIP release which was similar in specificity to the active
glucose transport system.
Two water soluble extracts GS3 and GS4 obtained from the leaves of Gymnema
sylvestre, were
tested in streptozotocin treated rats for their effects on blood glucose homeostasis and
pancreatic endocrine tissue. In the diabetic rats, fasting blood glucose levels returned to
normal after 60 days of GS3 and after 20 days of GS4 oral administration. In diabetic rat
pancreas, both therapy led to a rise in serum insulin to levels close to normal testing
levels. In diabetic rats pancreas both GS3 and GS4 doubled the islet number and beta cell
number. This herbal therapy appeared to bring about blood glucose homeostasis through
increased serum insulin levels provided by repair/regeneration of the endocrine pancreas.
Clinical trials:
In a clinical trial conducted on 27 patients with insulin-dependent Diabetes mellitus
(IDDM) on insulin therapy, GS4 a water soluble extract of the leaves of Gymnema
sylvestre was administered at a dosage of 400 mg/day. Insulin requirements came down
together with fasting blood glucose and glycosylated haemoglobin(HBA1c) and
glycosylated plasma protein levels, while serum lipids returned to near normal level with
GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels remained
higher than controls. IDDM pateints on insulin therapy showed no significant reduction
in serum lipids, HBA1c or glycosylated plasma proteins. GS4 therapy appeared to
enhance endogenous insulin , possibly by regeneration/revitalization of the residual beta
cells in insulin-dependent Diabetes mellitus.
Further clinical studies were conducted to test the effectiveness of GS4 therapy an extract
from the leaves of Gymnema sylvestre in controlling hyperglycaemia in 22 patients with
Type2 Diabetes (NIDDM -Non-insulin dependent Diabetes mellitus) on conventional
oral anti-hyperglycaemic agents. GS4 (400mg/day) was administered for 18 - 20 months
as a supplement to the conventional oral drugs. During GS4 supplementation, the patients
showed a significant reduction in blood glucose, glycosylated haemoglobin and
glycosylated plasma proteins and conventional drug dosage could be reduced. Five of the
22 diabetic patients were able to discontinue their conventional drug and maintain their
blood glucose homeostatis with GS4 alone. These data suggested the beta cells
regeneration/repair in Type 2 diabetic patients on GS4 supplementation, which is further,
supported by the appearance of raised insulin levels in the serum of patients after GS4
supplementation.
In another clinical trial hypoglycaemic activity of indigenous drug (Gymnema sylvestre)
was
evaluated in ten normal and six diabetic patients. They were subjected to glucose
tolerance test and venous blood samples were collected at 30 minutes intervals upto 2
hours. Aqueous decoction of the leaves was given at a dosage of 2g thrice daily for a
period of 10 days in healthy volunteers and in diabetic patients with mild to moderate
hyperglycaemic the above doses were given for 15 days.
Administration of the extract brought about a significant reduction in the fasting blood
sugar levels in normal and diabetic patients, which suggested a definite hypoglycaemic
activity.
The hypoglycaemic effect of Gymnema sylvestre was studied in 16 normal subjects and
in 43 mild diabetic patients. All the subjects were administered with leaf powder 10g/day
for 7 days. The results indicate that Gymnema sylvestre leaf powder has a hypoglycaemic
effect comparable to tolbutamide. Serum triacylglycerol, free fatty acids and cholesterol
levels in normal subjects were unaffected where as in diabetic patients it was
significantly decreased. Ascorbic acid and iron levels were elevated significantly in both
groups, where as excretion of creatine decreased in diabetic patients, this remained
unaffected in normal healthy volunteers.
Hypolipidaemic activity :
Leaf extract at a dosage of 25-100 mg/kg administered orally to experimentally induced
hyperlipidaemic rats for two weeks reduced the elevated serum trigylceride (TG), total
cholesterol (TC), very low density lipoprotein(VLDL) and low density lipoprotein(LDL)-
cholesterol in a dose dependent manner. The ability of the extract at 100mg/kg to lower
TG and TC in serum and its antiantheroscelrotic potential were almost similar to that of a
standard lipid lowering agent clifibrate.
(i) Toxicity: The LD50 of ethanol and water extract of Gymnema administered
intraperitoneally in mice was found to be 375mg/kg.
(j) Phytochemistry : The major bioactive constituents of Gymnema sylvestris are a group
of oleanane type triterpenoid saponins known as “gymnemic acids”1-2. The latter contain
several acylated (tigloyl, methylbutyroyl etc.,) derivatives of deacylgymnemic acid
(DAGA) which is 3-o- b- glucuronide of gymnemagenin (3b, 16b, 21b, 22a, 23, 28-
hexahydroxy-olean-12-ene). The individual gymnemic acids (saponins) include
gymnemic acids I-VII, gymnemosides A-F,
gymnemasaponins1-3 etc.,

ANALYTICAL SPECIFICATION OF CRUDE DRUG

Organoleptic characterization:
Colour : Green to yellowish green when completely dried
Odour : Odourless
Taste : Extremely bitter in taste
ESTIMATION OF GYMNEMIC ACIDS IN GYMNEMA SYLVESTRIS
EXTRACT
I. By Gravimetry method:
 Weigh 3.00 gm of the extract into a beaker.
 Dissolve in 50 ml distilled water, filter and to the filterate add 10% hydrochloric
acid till pH 1.5.
 Allow to stand for 30 minutes at room temperature.
 Filter on Whatman No. 1 filter paper.
 Wash with 20 ml distilled water and discard the filterate.
 Collect the precipitate and dissolve in 20ml 80.0% v/v ethanol or methanol.
 Combine the filterate and washing, evaporate in pre-weighed beaker and dry in
oven under vaccum at 70o C to a constant weight.
 Weigh and calculate the percentage of total gymnemic acid.
II. High Performance Liquid Chromatography (HPLC) method:
The major bioactive constituents of Gymnema sylvestris are a group of oleanane type
triterpenoid saponins known as “gymnemic acids”. Non-availability of the different
reference standards makes the job more difficult, therefore the estimation of the different
gymnemic acids is performed by hydrolyzing the extract first with alkali and then with
acid. The gymnemagenin thus obtained is estimated by HPLC and the total gymnemic is
calculated by applying the molecular weight corrections.
Gymnema Therapeutic Uses
1. Suppresses the taste of sweet foods, and consequently the desire to eat
2. Reduces the metabolic effect of sugar by preventing the intestines from absorbing
sugar molecules during digestion
3. Treatment of diabetes
4. Snakebite, treated by powder or paste of the root applied to the wound.
5. Fever, treated with oral administration of half announce to an ounce (one part in
10) of leaves.
6. Swollen glands, treated with an external application of triturated leaves mixed
with castor oil.
7. Gymnema helps to normal blood sugar
8. Gymnema controls sugar level
9. Gymnema controls and regulate weight
10. Gymnema controls sugar craving
11. Gymnema reduces the taste of sugar when it is on the mouth
12. Gymnema curb sweet tooth
13. Gymnema for blood glucose
14. Gymnema for Cholesterol
15. Gymnema is the natural way to help control blood sugar
16. Gymnema neutralized the craving for sweets by abolishing the taste of sugar
17. Gymnema promotes regeneration of beta cells responsible for releasing insulin in
the pancreas
18. Gymnema prevents adrenaline from stimulating the liver to produce glucose
19. Gymnema lowers serum cholesterol and triglycerides
Trigonella foenum-graeceum
Trigonella foenum-graeceum commonly known as fenugreek has been used since ancient
times both as a food and medicine. In India the young shoots form a favorite vegetable.
Clinically the effects of extracts of Fenugreek seeds is proven in 25 diabetes patient (type
2 diabetes). It was demonstrated that adjunct use of fenugreek seeds improved glycemic
control and decreased insulin resistance in mild type-2 diabetic patients. Another clinical
studies, effect of fenugreek seeds on blood glucose and the serum lipid profile was
evaluated in insulin-dependent (Type I) diabetic patients. The fenugreek diet significantly
reduced fasting blood sugar and improved the glucose tolerance test. There was a 54 per
cent reduction in 24-h urinary glucose excretion. Serum total cholesterol, LDL and
VLDL cholesterol and triglycerides were also significantly reduced.
Preclinical studies demonstrates that the therapeutic role of fenugreek seed powder in
type-1 diabetes can be attributed to the change of glucose and lipid metabolizing enzyme
activities to normal values, thus stabilizing glucose homeostasis in the liver and kidney.