Anti-Diabetic Activity of Fruits of Terminalia chebula on Streptozotocin Induced Diabetic Rats

Abstract

The present study was aimed to evaluate the anti-diabetic potential of Terminalia chebula (T. chebula) fruits on streptozotocin (STZ)-induced experimental diabetes in rats. Oral administration of ethanolic extract of the fruits (200 mg/kg body weight/rat/day) for 30 days significantly reduced the levels of blood glucose and glycosylated hemoglobin in diabetic rats. Determination of plasma insulin levels revealed the insulin stimulating action of the fruit extract. Also, the alterations observed in the activities of carbohydrate and glycogen metabolising enzymes were reverted back to near normal after 30 days of treatment with the extract. Electron microscopic studies showed significant morphological changes in the mitochondria and endoplasmic reticulum of pancreatic β cells of STZ-induced diabetic rats. Also, a decrease in the number of secretory granules of β-cells was observed in the STZ-induced diabetic rats and a these pathological abnormalities were normalized after treatment with T. chebula extract. The efficacy of the fruit extract was comparable with glibenclamide, a well known hypoglycemic drug.

Full text

283
Journal of Health Science, 52(3) 283–291 (2006)
INTRODUCTION
Diabetes mellitus (DM) is considered as one of
the five leading causes of death in the world. About
150 million people are suffering from diabetes
worldwide, which is almost five times more than
the estimates ten years ago and this may double by
the year 2030. India leads the way with its largest
number of diabetic subjects in any given country. It
has been estimated the number of diabetes in India
is expected to increase 57.2 million by the year
2025.1) Diabetes is a complex multisystemic disor-
der characterized by a relative or absolute insuffi-
ciency of insulin secretion insulin dependent diabe-
tes mellitus (IDDM) or concomitant resistance of
the metabolic action of insulin on target tissues2) non
insulin dependent diabetes mellitus (NIDDM).
Insulin therapy affords glycemic control in
IDDM yet its short comings include ineffectiveness
on oral administration, short shelf life, need for pres-
ervation in refrigeration, fatal hypoglycemia in the
event of excess dosage, reluctance to take injection
and above all, the resistance due to prolonged ad-
ministration, limits its usage. Similarly treatment of
NIDDM patients with sulfonylureas and biguanides
is always associated with side effects.3) Hence, search
for a drug with low cost, more potentials, and with-
out adverse side effects is being pursued in several
laboratories around the world.
Throughout the world many traditional plants
have been found successful for antidiabetic activity.
Further, most of the marketed medicines are distil-
lations, combinations, reproductions or variations of
substances that are found in nature. Our forefathers
recommended some of the substances, which are
abundantly found in nature long before their value
was demonstrated and understood by scientific meth-
ods. However, few have received scientific or medi-
cal scrutiny and the World Health Organization
(WHO) has recommended the traditional plant treat-
ments for diabetes warrant further evaluation.4)
Moreover, today it is necessary to provide scientific
proof as to whether it is justified to use a plant or its
active principles for treatment.5)
Terminalia chebula (T. chebula) Retz
(Combretaceae), a native plant in India and South-
east Asia, is extensively cultivated in Taiwan. Its
dried ripe fruit, has traditionally been used to treat
various ailments in Asia.6) It is a popular folk medi-
Anti-Diabetic Activity of Fruits of
Terminalia
chebula
on Streptozotocin Induced Diabetic Rats
Gandhipuram Periasamy Senthil Kumar, Palanisamy Arulselvan, Durairaj Sathish Kumar,
and Sorimuthu Pillai Subramanian*
Department of Biochemistry and Molecular Biology, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India
(Received February 10, 2006; Accepted March 21, 2006)
The present study was aimed to evaluate the anti-diabetic potential of Terminalia chebula (T. chebula) fruits on
streptozotocin (STZ)-induced experimental diabetes in rats. Oral administration of ethanolic extract of the fruits
(200 mg/kg body weight/rat/day) for 30 days significantly reduced the levels of blood glucose and glycosylated
hemoglobin in diabetic rats. Determination of plasma insulin levels revealed the insulin stimulating action of the
fruit extract. Also, the alterations observed in the activities of carbohydrate and glycogen metabolising enzymes
were reverted back to near normal after 30 days of treatment with the extract. Electron microscopic studies showed
significant morphological changes in the mitochondria and endoplasmic reticulum of pancreatic
β
cells of STZ-
induced diabetic rats. Also, a decrease in the number of secretory granules of
β
-cells was observed in the STZ-
induced diabetic rats and a these pathological abnormalities were normalized after treatment with T. chebula extract.
The efficacy of the fruit extract was comparable with glibenclamide, a well known hypoglycemic drug.
Key words —–— diabetes, Terminalia chebula, ethanolic extract, carbohydrate metabolism, electron microscope
*To whom correspondence should be addressed: Department of
Biochemistry and Molecular Biology, University of Madras,
Guindy Campus, Chennai-600 025, Tamil Nadu, India. Tel. &
Fax: +91-44-22300488; E-mail: subbus2020@yahoo.co.in

284 Vol. 52 (2006)
cine and has been studied for its homeostatic laxa-
tive, diuretic and cardiotonic activities.7,8)
T. chebula has been reported to exhibit a variety
of biological activities, including antidiabetic,9) an-
ticancer,10) antimutagenic11,12) and antiviral13) activ-
ity. However, no systematic work on its anti-diabe-
togenic activity has been reported in the literature.
Hence, the present study was aimed to evaluate the
pharmacological effect of ethanolic extract of T.
chebula on carbohydrate and glycogen metabolism
in both normal and streptozotocin (STZ)-induced
diabetic rats. The effects of T. chebula are compared
to glibenclamide that is often used as a standard drug.
MATERIALS AND METHODS
Chemicals —–— Streptozotocin was purchased from
Sigma Chemical Co., St. Louis, MO, U.S.A. Radio-
immunoassay kit for insulin assay was obtained from
Linco Research Inc., U.S.A. All the other chemicals
used were of analytical grade.
Plant Material —–— Fresh mature T. chebula fruits
were collected from a tree in Kolli Hills, Namakkal
District, Tamil Nadu, India. The plant was identi-
fied and authenticated by Dr. K. Kaviyarasan, CAS
in Botany, University of Madras, and a voucher
specimen was deposited at the herbarium of Botany.
Preparation of T. chebula Fruit Extract —–— Dried
fruits were powdered in an electrical grinder and
stored at 5°C until further use. 100 g of the powder
was extracted with petroleum ether (60–80°C) to
remove lipids. It was then filtered and the filtrate
was discarded. The residue was extracted with 95%
ethanol by Soxhlet extraction. The ethanol was
evaporated in a rotary evaporator at 40–50°C under
reduced pressure. The yield of the extract was 8.5 g/
100 g.
Animals —–— Adult male albino rats of Wistar strain
weighing approximately 150 to 180 g were procured
from Tamil Nadu Veterinary and Animal Sciences
University, Chennai, India. They were acclamatized
to animal house conditions, fed with standard rat feed
supplied by Hindustan Lever Ltd., Bangalore, In-
dia. All the animal experiments were conducted ac-
cording to the ethical norms approved by Ministry
of Social Justices and Empowerment, Government
of India and Institutional Animal Ethics Committee
guidelines (Approval No. 01/030/04).
Toxicity Studies —–— To study any possible toxic
effects and/or changes in behavioural pattern, rats
were treated with graded dose of T. chebula extract
(100–500 mg/kg body weight/rat/day) and kept un-
der close observation for 8 hr daily for 30 days. All
symptoms including changes in awareness, mood,
motor activity, posture, motor-co-ordination, muscle
tone and reflexes were recorded for 30 days.
Induction of Experimental Diabetes —–— T h e
animals were fasted overnight and diabetes was
induced by a single intraperitoneal injection
of a freshly prepared solution of Streptozotocin
(55 mg/kg body weight) in 0.1 M cold citrate buffer
(pH 4.5).14) The animals were allowed to drink 5%
glucose solution overnight to overcome the drug-
induced hypoglycemia. Control rats were injected
with citrate buffer alone. After a week time for the
development of diabetes, the rats with moderate dia-
betes having glycosuria and hyperglycemia (blood
glucose range above 250 mg/dl) were considered as
diabetic and used for the drug treatment. The fruit
extract in aqueous solution was administered orally
through a gavage at a concentration of 200 mg/kg
body weight/rat/day for 30 days.
Experimental Design —–— The animals were di-
vided into two sets, one for the evaluation of a glu-
cose tolerance test and a second one for the analysis
of biochemical parameters. Each set was further di-
vided into four groups; each comprising a minimum
of six animals in each group as detailed below:
Group I: Normal control rats.
Group II: Diabetic control rats.
Group III: Diabetic rats given T. chebula fruit
extract (200 mg/kg body weight/day/rat) in aqueous
solution orally for 30 days.
Group IV: Diabetic rats administered with
glibenclamide (600
µ
g/kg body weight/day/rat) in
aqueous solution orally for 30 days.15)
The body weight gain and fasting blood glucose
levels of all the rats were recorded at regular inter-
vals during the experimental period.
Glucose Tolerance Test —–— After 30 days of treat-
ment, a fasting blood sample was collected from all
the groups in heparinized tubes. Blood samples were
also collected at the time intervals of 30, 60, 90 and
120 min after administration of glucose at a concen-
tration of 2 g/kg of body weight.16)
Biochemical Assays —–— After 30 days of treat-
ment, the fasted rats of various groups were sacri-
ficed by cervical decapitation. Fasting blood glucose
was estimated by the O-toluidine method of Sasaki
et al.17) The levels of hemoglobin and glycosylated
hemoglobin were estimated according to methods
of Drabkin et al.18) and Nayak et al.19) respectively.
Plasma insulin was estimated by using a radioim-

285
No. 3
munoassay kit.
A portion of the liver tissue was dissected,
washed with ice cold saline and homogenized in
0.1 M Tris–HCl buffer, pH 7.4. The supernatant was
used for the assay of enzyme activity. The hexoki-
nase activity was assayed by the method of
Brandstrup et al.20) The activities of glucose-6-phos-
phatase and fructose-1,6-bisphosphatase were as-
sayed according to the method of Koide and Oda21)
and Gancedo and Gancedo,22) respectively. The
King23) method was adopted for the assay of lactate
dehydrogenase (LDH) activity. Glycogen synthase
and phosphorylase activities were assayed by the
method of Leloir and Goldenberg24) and Cornblath
et al.,25) respectively. Another portion of wet liver
tissue was used for the estimation of glycogen by
the method of Morales et al.26)
Electron Microscopy Studies —–— For electron
microscopic examination of pancreas, primer fixa-
tion was made in 3% glutaraldehyde in sodium phos-
phate buffer (200 mM, pH 7.4) for 3 hr at 4°C. Ma-
terials were washed with same buffer and postfixed
in 1% osmium tetroxide and in sodium phosphate
buffer (pH 7.4) for 1 hr at 4°C. Tissue samples were
washed with same buffer for 3 hr at 4°C, and were
dehydrated in graded ethanol series and were em-
bedded in Araldite. 60–90 nm sections (60–90 nm)
were cut on an LKBUM4 ultramicrotome using a
diamond knife and sections were mounted on a cop-
per grid and stained with uranyl acetate and Reynolds
lead citrate.27) The grids were examined under a
Phillips electron microscope model 201C (EM201C)
transmission electron microscope.
Statistical Analysis —–— All the grouped data were
statistically evaluated with statistical package for
social sciences (SPSS)/10 software. Hypothesis test-
ing methods included one-way analysis of variance
(ANOVA) followed by least significant difference
(LSD) test; P values of less than 0.05 were consid-
ered to indicate statistical significance. All the re-
sults were expressed as the mean ± standard devia-
tion (S.D.) for six animals in each group.
RESULTS
Acute toxicity studies conducted by us (data not
shown) revealed that the administration of graded
doses of T. chebula fruit extract (up to a dosage of
500 mg/kg body weight/day) for 30 days produced
no effect on the general behaviour or appearance of
the animals and all the rats survived the test period.
There were no signs and symptoms such as restless-
ness, respiratory distress, diarrhea, convulsions,
coma. Assay of pathophysiological enzymes such
as alkaline phosphatase (ALP), aspartate transami-
nase (AST) and alanine transaminase (ALT) in
plasma revealed the nontoxic nature of fruit extract.
Figure 1 shows the change in body weight gain
of control and experimental groups of rats. There
was a significant decrease in the body weight of dia-
betic rats compared with control rats. Upon treat-
ment with T. chebula and glibenclamide, the body
weight gain was improved but the effect was
more pronounced in T. chebula treated rats than
glibenclamide.
Fig. 1. Changes in Body Weight of Control and Experimental Groups of Rats
Values are given as mean + S.D. for groups of six rats each. Values are statistically significant at *p< 0.05, Diabetic control rats were compared with
control rats. Diabetic + T. chebula and diabetic + glibenclamide treated rats were compared with diabetic control rats.

286 Vol. 52 (2006)
The levels of blood glucose in control and ex-
perimental groups of rats after oral administration
of glucose is shown in Fig. 2. The blood glucose
value in the control rats rose to a peak value 60 min
after glucose load and decreased to near normal lev-
els at 120 min. In diabetic control rats, the peak in-
crease in blood glucose concentration was observed
after 60 min and remained high over the next 60 min.
T. chebula and glibenclamide treated diabetic rats
showed significant decrease in blood glucose con-
centration at 60 and 120 min compared with diabetic
group of rats.
Table 1 shows the level of blood glucose, plasma
insulin, total hemoglobin, glycosylated hemoglobin
and urine sugar in normal and experimental groups
of rats. There was a significant elevation in blood
glucose, urine sugar and glycosylated hemoglobin,
while the level of plasma insulin and total hemoglo-
bin decreased during diabetes when compared to
control group. Administration of T. chebula brought
back to near normal values as that of standard drug
glibenclamide treatment.
Table 2 depicts a significant decrease in the ac-
tivity of hepatic hexokinase, a significant increase
in the activities of lactate dehydrogenase, glucose-
6-phosphatase and fructose-1,6-bisphosphatase in
STZ-induced diabetic rats when compared to con-
trol rats. Treatment with T. chebula extracts (group
III) and glibenclamide (group IV) significantly con-
trolled the alterations and restored the altered levels
to near normalcy. T. chebula treatment exerted more
effect than glibenclamide in diabetic rats.
Table 3 presents the changes in hepatic glyco-
gen content and in the activities of glycogen syn-
thase and glycogen phosphorylase in the hepatic tis-
sue of control and experimental group of rats. A sig-
Fig. 2. Glucose Tolerance Test Curve of Control and Experimental Groups of Rats
Blood sample collected at 0, 30, 60, 90 and 120 min intervals after administration of glucose (2 kg/body weight) were assayed for glucose content.
Values are given as mean ± S.D. for groups of six animals each; Values are statistically significant at *p< 0.05; Diabetic control rats were compared with
control rats; diabetic + T. chebula and diabetic + glibenclamide treated rats were compared with diabetic control rats.
Table 1. Changes in the Level of Blood Glucose, Plasma Insulin, Hemoglobin, Glycosylated Hemoglobin and Urine Sugar in Control
and Experimental Groups of Rats
Groups Blood glucose Plasma insulin Hemoglobin Glycosylated Urine sugar
milligram/deciliter microunit/milliliter (g/dl) hemoglobin
(mg/dl) ( U/ml) (% HbA
1
c)
Control 85.43 5.72 16.54 1.07 13.52 0.81 6.24 0.38 Nil
Diabetic control 265.08 20.14* 5.27 0.76* 9.25 0.67* 12.36 0.91* +++
Diabetic + T. chebula 92.30 6.09* 15.26 0.71* 12.93 0.82* 6.72 0.42* Nil
Diabetic + Glibenclamide 102.40 6.45* 13.86 0.62* 12.46 0.77* 6.95 0.42* +
Values are given as mean S.D. for groups of six animals in each group. Values are statistically significant at *p005. Diabetic control
rats were compared with control rats. Diabetic + T. chebula and diabetic + glibenclamide treated rats were compared with diabetic control rats. (+)
indicate 0.25% sugar and (+++) indicates more than 2% sugar.

287
No. 3
nificant decrease in liver glycogen content and gly-
cogen synthase activity and concomitant increase in
the activity of glycogen phosphorylase was observed
in the diabetic group of rats and it was normalized
after treatment.
A decrease in the number of secretory granules
of
β
-cells was observed in diabetic group (Fig. 3)
when compared to the control group (Fig. 4). Also
severely decreased secretory granules, severe de-
struction of nuclear membrane and degenerative
changes in the core of islet cells and nucleus were
observed in STZ-induced diabetic rats. However,
diabetic rats treated with T. chebula extract showed
apparently normal cell architecture (Fig. 5). It simi-
lar observations have also been observed in diabet-
ics rats treated with glibenclamide (Fig. 6).
DISCUSSION
Streptozotocin is well known for its selective
pancreatic islet
β
-cell cytotoxicity and has been ex-
tensively used to induce Type-1 diabetes in experi-
mental rat model. It interferes with cellular meta-
bolic oxidative mechanisms.28) Increasing evidence
in both experimental and clinical studies suggests
that oxidative stress plays a major role in the devel-
opment and progression of both types of diabetes
mellitus. Free radicals are formed disproportionately
in diabetes by glucose oxidation, non enzymatic
glycation of proteins and subsequent oxidative deg-
radation of glycation proteins. Diabetes is usually
accompanied by impaired antioxidant defenses.
Fig. 3. Swelling of Mitochondria (M), Decreased Secretory
Granules (G), Clear Vesicles (→) in Electron Micrograph
from of the Diabetic Rat
Magnification: × 15000.
Table 3. Level of Glycogen, Activities of Glycogen Synthase and Glycogen Phosphorylase in the Liver Tissue of Control and Experi-
mental Groups of Rats
Groups Glycogen Glycogen synthase (micromole Glycogen phosphorylase
(mg of glucose/g of uridine diphosphate (micromole of phosphate
of wet tissue) formed/hr/mg protein) liberate/hr/mg protein)
Control 58.23 3.55 845.62 69.34 612.18 50.19
Diabetic control 26.80 1.95* 567.43 50.50* 870.64 80.09*
Diabetic + T. chebul a 56.28 3.54* 812.12 68.21* 653.23 54.87*
Diabetic + Glibenclamide 50.95 3.20* 786.56 66.85* 713.51 57.79*
Values are given as mean S.D. for groups of six animals in each group. Values are statistically significant at *p005. Diabetic control
rats were compared with control rats. Diabetic + T. chebula and diabetic + glibenclamide treated rats were compared with diabetic control rats.
Table 2. Changes in the Activities of Hepatic Hexokinase, Lactate Dehydrogenase, Glucose-6-phosphatase and Fructose 1,6-
Bisphosphatase of Control and Experimental Groups of Rats
Groups Hexokinase Lactate dehydrogenase Glucose-6-phosphatase Fructose 1,6-
(micromole Glucose- (micromole pyruvate (micromole phosphate bisphosphatase (micromole
6-phosphate formed formed/hr/mg liberated/hr/mg protein) phosphate liberated/
hr/mg protein) protein) hr/mg protein)
Control 273.6 16.68 248.23 15.88 1042 84.40 482 29.88
Diabetic control 139.3 10.58* 356.45 27.09* 1968 184.99* 749 55.42*
Diabetic + T. chebul a 270.1 17.28* 253.92 16.00* 1061 88.06* 502 31.62*
Diabetic + Glibenclamide 257.4 17.50* 268.37 16.90* 1216 103.36* 531 33.98*
Values are given as mean S.D. for groups of six animals in each group. Values are statistically significant at *p005. Diabetic control
rats were compared with control rats. Diabetic + T. chebula and diabetic + glibenclamide treated rats were compared with diabetic control rats.

288 Vol. 52 (2006)
Glibenclamide is often used as a standard antidia-
betic drug in STZ-induced moderate diabetes to com-
pare the efficacy of variety of hypoglycemic com-
pounds.29) The present study was conducted to as-
sess the hypoglycemic activity T. chebula fruits in
STZ-induced diabetic rats. The ability of T. chebula
fruit extract in significantly increasing the body
weight and effectively controlling the increase in
blood glucose levels in diabetic group of rats may
be attributed to its antihyperglycemic effects. Fur-
ther, the antihyperglycemic activity of T. chebula was
associated with an increase in plasma insulin level,
suggesting an insulinogenic activity of the fruit ex-
tract. The observed increase in the level of plasma
insulin indicates that T. chebula fruit extract stimu-
lates insulin secretion from the remnant
β
-cells or
from regenerated
β
-cells. In this context, a number
of other plants have also been reported to exert hy-
poglycemic activity through insulin release stimu-
latory effect.30,31)
The observed increase in the levels of
glycosylated hemoglobin (HbA1c) in diabetic con-
trol group of rats is due to the presence of excessive
amounts of blood glucose. During diabetes the ex-
cess of glucose present in blood react with hemo-
globin to form glycosylated haemoglobin.32,33)
Mechanisms by which increased oxidative stress is
involved in the diabetic complications are partially
known, including activation of transcription factors,
advanced glycated end products (AGEs), and pro-
tein kinase C. Glycosylated hemoglobin has been
found to be increased over a long period of time in
the diabetic mellitus.34) There is an evidence that
glycation may itself induce the generation of oxy-
gen-derived free radicals in diabetic condition.35)
Treatment with T. chebula extract showed a decrease
in the glycosylated hemoglobin with a concomitant
increase in the level of total hemoglobin in the dia-
betic rats standard drug glibenclamide also showed
the same results.
Liver plays an important role in the maintenance
of blood glucose level by regulating its metabolism.
Hexokinase, which brings about the first phospho-
rylation step of glucose metabolism, is reduced sig-
nificantly in the diabetic group of rats.36) This may
be the reason for the diminished consumption of glu-
cose in the system and increased blood sugar level.
In STZ-induced diabetic rats, the hexokinase syn-
thesis is decreased due to low levels of mRNA cod-
ing for the hexokinase and insulin administration
stimulated transcription of hexokinase mRNA syn-
thesis and thus enhanced the rate of synthesis and
Fig. 4. Electron Micrograph of a Normal
β
-Cell in the Control
Rat
Magnification: × 15000.
Fig. 6. Normal Mitochondria (M), Normal Nucleus (N) and
Increased Secretory Granules (G) in the Diabetic Group
Given Glibenclamide
Magnification: × 15000.
Fig. 5. Apparently Normal Mitochondria (M), Normal Nucleus
(N) and Increased Secretory Granules (G) in the Dia-
betic Group Given T. chebula
Magnification: × 15000.

289
No. 3
activity of the enzyme.37) The mechanism played by
T. chebula extract in enhancing the hexokinase ac-
tivity could be due to the activation of mRNA cod-
ing for hexokinase in diabetic rats.
Lactate dehydrogenase in anaerobic glycolysis,
catalyses the conversion of pyruvate to lactate which
subsequently is converted to glucose in gluconeo-
genic flux. In diabetic condition, an increased activ-
ity of lactate dehydrogenase was observed.38,39) The
LDH system reflects the Nicotinamide adenine di-
nucleotide/reduced nicotinamide adenine dinucle-
otide (NAD+/NADH) ratio indicated by the lactate/
pyruvate ratio of hepatocyte cytosol.40) In T. chebula
extract and glibenclamide treated group of rats, the
reduction in the LDH activity is probably due to the
regulation of NAD+/NADH ratio by oxidation of
NADH.
The hepatic gluconeogenic enzymes, glucose-
6-phosphatase and fructose-1,6-bisphosphatase were
increased significantly in diabetic rats. The increased
activities of these two gluconeogenic enzymes in
liver may be due to the activation or increased syn-
thesis of the enzymes contributing to the increased
glucose production during diabetes by the liver.41)
The therapeutic role of T. chebula and glibenclamide
may be due to its primarily modulating and regulat-
ing
δ
activities of the two gluconeogenic enzymes,
either through the regulation by 3′,5′-cyclic adenos-
ine monophosphate (cyclic AMP) and any other
metabolic activation or inhibition of glycolysis and
gluconeogenesis.
The conversion of glucose to glycogen in the
liver cells is dependent on the extracellular glucose
concentration and on the availability of insulin which
stimulates glycogen synthesis over a wide range of
glucose concentration.42) The regulation of glycogen
metabolism in vivo occurs by the multifunctional
enzyme glycogen synthase and glycogen phospho-
rylase that play a major role in the glycogen me-
tabolism.43) The reduced glycogen store in diabetic
rats has been attributed to reduced activity of glyco-
gen synthase44) and increased activity of glycogen
phosphorylase.45) In the present study the experimen-
tal diabetic rats treated with T. chebula extract and
glibenclamide treated groups restored the level of
hepatic glycogen by means of decreasing the activ-
ity of glycogen phosphorylase and increasing the
activity of glycogen synthase. This coincides with
the previous work in our laboratory.46)
In the diabetic group of rats treated with T.
chebula extract, an increase in the number of
β
-cells
in the islets shows that they were regenerated. Also,
the increase in secretory granules in the cells indi-
cates that the cells were stimulated for insulin syn-
thesis. A decrease in the number of secretory gran-
ules, nuclear shrinkage and pycnosis, swelling of
mitochondria and endoplasmic reticulum, round-
shaped mitochondria, hypertrophied cytoplasmic
organelles such as golgi and endoplasmic reticulum
have been reported in the
β
cells of STZ-induced
diabetic rats.47,48) Our results are also inline with the
previous report.
In conclusion, the present study shows that the
ethanolic extract of T. chebula fruit has potential
hypoglycemic action in STZ-induced diabetic rats
and the effect was found to be more effective than
glibenclamide Further, studies are in progress at
molecular level to explicitly explain more about the
mechanism of the antidiabetic activity of T. chebula
and compounds responsible for its antidiabetic ef-
fect.
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