Int J Endocrinol Metab 2006; 4: 96-105

ORIGINAL ARTICLE
Effects of Syzygium Cumini Bark on Blood Glucose,
Plasma Insulin and C-peptide in Streptozotocin-
induced Diabetic rats

Saravanan G, Leelavinothan P.

D
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai Univer-

SI
sity, Annamalainagar-608002, Tamil Nadu, India

I
n recent years, several plant extracts have nificantly in diabetic rats as compared to normal
been examined for their antidiabetic rats. Oral administration of SBEt exhibited
propertics in an effort to identify alterna- antidiabetic activity by significantly (p<0.05)
tive treatment strategies that pose less of a lowering blood glucose (84.30±4.25) and urine
of
risk for diabetics. The present study was under- sugar levels in diabetic rats. Additionally, dia-
taken to investigate the antidiabetic effects of betic rats treated with SBEt had significantly
Syzygium cumini bark in experimental diabetes (p<0.05) elevated levels of plasma insulin
mellitus. (10.29±0.59) and C-peptide (236.50±11.87). During
Materials and Methods: Diabetes was induced in OGTT, long-term administration of SBEt was
ive

male albino Wistar rats by a single intraperito- able to significantly (p<0.05) decrease blood glu-
neal injection of streptozotocin (45 mg/kg body cose concentrations (93.94 ± 3.17; 120min) at vari-
weight), after which, the animals were randomly ous time intervals when compared to the OGTT
allocated into five experimental groups as fol- pattern of diabetic rats (316.03 ± 18.03). As com-
lows: Group 1: normal rats, Group 2: normal rats pared to glibenclamide, SBEt has better antidia-
received Syzygium cumini bark extract (SBEt; betic effects.
ch

300mg/kg body weight), Group 3: diabetic con- Conclusions: The findings of this study indicate
trol rats, Group 4: diabetic rats receiving SBEt that the antidiabetic activity of SBEt, and both
(300mg/kg), Group 5: diabetic rats received the pancreatic and the extrapancreatic mecha-
glibenclamide (600µg/kg body weight). The ef- nisms might be involved such apparent dual ac-
fects of 45 days treatment of SBEt on blood glu- tions of SBEt would be more advantageous to
Ar

cose, plasma insulin, C-peptide, urine sugar and the existing oral antidiabetic monotherapy.
body weight were studied in comparison to
those of glibenclamide. Key Words: Syzygium cumini, Antidiabetic ef-
Results: Blood glucose levels (268.10±19.25 mg/dL) fect, Streptozotocin diabetes, Blood glucose, Oral
and urine sugar increased significantly whereas
glucose tolerance test, Plasma insulin, C-peptide
the levels of plasma insulin (5.01±0.29 µU/L) and
C-peptide (167.68± 8.50 pmol/L) decreased sig- Received: 15/06/2006- Accepted: 21/08/2006
Correspondence:L.Pari, Department of Biochemistry
and Biotechnology, Faculty of Science, Annamalai
University, Annamalainagar-608002, Tamil Nadu,
India
E-mail: pariau@rediffmail.com

www.SID.ir
 Antidiabetic action of Syzygium Cumini Bark 97

Introduction following the side effects associated with the

Variability is an inherent characteristic of existing therapeutic agents.8,9 The investiga-
the biological world. Globally we are facing tion of antidiabetic agents of plant origin
an epidemic of non-communicable diseases, normally used in traditional medicine is thus
which will soon surpass communicable dis- of great importance.
eases both in the developing and the devel- In Asia and South America, the develop-
oped world.1 Diabetes mellitus, once consid- ment and use of cheap and easily accessible
ered a disease of minor significance to world phytomedicines from plants of the genus
health, is now a major threat to human health Syzygium in the treatment of diabetes is en-
in the 21st century.2 A recent study by the visaged to circumvent these problems.10
World Health Organization (WHO) estimated Syzygium cumini (Linn.) Skeels (Synonym:
that the worldwide prevalence of diabetes in Eugenia jambolana Lam.), a member of fam-
2002 was 170 million, with the number pre- ily Myrtaceae commonly known as Jamun or
dicted to grow to 366 million or more by Jambul in Hindi and Black Plum or Black
2030. The adoption of a sedentary lifestyle, Berry in English, is a large size evergreen

D
the consumption of non-traditional foods and, tree indigenous to India and is cultivated in
a genetic predisposition to the disease are gardens for its delicious fruit. Besides India,
thought to be the major underlying causes of it is also found in South-East Asia and East-

SI
the epidemic.3,4 ern Africa.11,12 Out of a large number of
Diabetes mellitus is a potentially devastat- herbal drugs stated to possess antidiabetic ac-
ing disease with high morbidity and mortality tivity in the Ayurvedic system of medicine of
rates. The central identifying feature of dia- India, S. cumini is being widely used by the
betes is chronic and substantial elevation of traditional practitioners to treat diabetes over
of
the circulating glucose concentration. The many centuries.13
long-term hyperglycaemia is an important Various parts of this plant have been rec-
factor in the development and progression of ognized for several medicinal properties in
microvascular and microvascular complica- folklore medicine. The bark of the plant is as-
tions.5 The underlying goal of all diabetes tringent, refrigerant, carminative, diuretic,
ive

treatment and management is to maintain an digestive, antihelminthic, febrifuge, consti-

adequate blood glucose concentration. Pro- pating, stomachic and antibacterial. The fruits
gress in understanding the metabolic staging and seeds are used to treat diabetes,
of diabetes over the past few years has led to pharyngitis, spleenopathy, urethrorrhea and
significant advances in regimen for treatment ringworm infection. The leaves are antibacte-
ch

of this devastating disease.6 Four major rial and used to strengthen the teeth and
classes of oral hypoglycaemic agents have gums. The leaves have also been extensively
been used extensively: insulin secretagogues, used to treat diabetes, constipation, leuco-
biguanides, thiazolidinediones, and α- rrhoea, stomachalgia, fever, gastropathy,
Ar

glucosidase inhibitors. Each drug class works strangury, dermopathy and to inhibit blood
on different mechanism of actions, including discharge in the faeces.14, 15
stimulation of insulin secretion, reduction of The plant S. cumini is frequently used for
hepatic gluconeogenesis, increase in insulin the treatment of diabetes; it has been shown
receptor sensitivity and delay of digestion that the bark, fruit, seeds or leaves of this
and absorption of carbohydrate, respec- plant collected from diverse regions of the
tively.7 Although various types of oral hypo- world and administered in different pharma-
glycemic agent are currently available along ceutical preparations (e.g., tinctures and
with insulin for treating diabetes mellitus, aqueous extracts) decrease blood glucose
there is a growing interest in herbal remedies levels in diabetic animals. In addition, infu-
sions (simple aqueous extracts prepared with

International Journal of Endocrinology and Metabolism

www.SID.ir
98 Ganeasn Saravana and Leelavinothan Pari

hot water but without boiling) and decoctions barium of the Botany Directorate, Faculty of
(boiled infusions) of S. cumini have been Science, Annamalai University. A voucher
used in traditional medicine for the treatment specimen was deposited in the Botany De-
of diabetes mellitus.16 Herbal drugs contain- partment of Annamalai University. The bark
ing S. cumini bark (a major ingredient) under was air dried at room temperature (25°C) and
the names ‘Cogent db’ and ‘D-400’ are also the dried bark was ground into fine powder
very popular traditional medicines for the with an auto-mix blender. The powdered part
treatment of diabetes.17, 18 This species has was kept in a deep freezer until the time of
been extensively investigated and a number use.
of chemical constituents from the fruits, Preparation of plant extract:
seeds, leaves, roots, flowers and bark of the 500 g of dry fine powder was suspended in
plant have often previously reported; these 1.5 L water and then stirred magnetically
include acetyl oleanolic acid, tannin, gallic overnight (12 h) at room temperature. The
acid, ellagic acid, quercetin, isoquercitin, extract was preserved and the processes were
kaempferol, myricetin flavonol glycoside, repeated three times consecutively with the

D
triterpenoids, saponins and anthocyanin.19-23 residual powder, collecting the extract each
In addition pharmacological evaluation of time. The collected extract was pooled and
this plant concerning its antidiabetic,24-27 passed through a fine cotton cloth. The fil-
hypolipidaemic,28-31 antioxidant,32-34 anti-

SI
trate upon evaporation at 40°C in a low-
HIV,35 anti-diarrheal,12 anti-inflammatory,36, pressure rotavapor (Rotavapor apparatus, Bu-
37
anti-bacterial,38 antipyretic,39 radioprotec- chi Labortechnik AG, Switzerland) yielded
tive23 and neuropsycho-pharmacological ac- 15% of semi-solid extract. It was stored at in
tivity have been shown.40 However, despite a refrigerator at 0°C - 4°C until used. When
of
the various bioactive phytochemical constitu- needed, the residual extract was suspended in
ents and diverse medicinal properties attrib- distilled water and used in the study.
uted to this plant, no detailed biochemical Experimental animals:
studies have been carried out to shed light on Adult male albino rats of Wistar strain
the role of S. cumini bark in diabetes. Hence, weighing approximately 80–200 g were ob-
ive

the present study was carried out in an at- tained from Central Animal House, Depart-
tempt to investigate the possible antidiabetic ment of Experimental Medicine, Faculty of
action of S. cumini bark in streptozotocin- Medicine, Rajah Muthiah Medical College,
induced diabetic rats. Annamalai University. The animals were
housed in polycarbonate cages in a room with
ch

Materials and Methods a 12 h day-night cycle, at a temperature of 22

Drugs and chemicals: ± 2˚C, and humidity of 45-64%. During the
Rat/Mouse insulin (ELISA) and C-peptide whole experimental period, animals were fed
(RIA) kits were obtained from Linco Re- with a balanced commercial diet (carbohy-
Ar

search Inc, USA. All other drugs and bio- drates 30%; proteins 22%; lipids 12%; vita-
chemicals used in this experiment were pur- mins 3%) (Hindustan Lever Ltd., Mumbai,
chased from Sigma Chemical Company Inc., India) and water ad libitum. All animal ex-
St Louis, Mo, USA. The chemicals were of periments were approved by the Ethical
analytical grade. Committee, Annamalai University and were
Plant material: in accordance with the guidelines of the Na-
S. cumini bark was freshly collected (dur- tional Institute of Nutrition, Indian Council of
ing August 2001) from plants grown in the Medical Research, Hyderabad, India. The
Botanical Garden of Annamalai University, rats received humane care according to the
Tamil Nadu, India. The plant was taxonomi- criteria outlined in the ‘Guide for the Care
cally identified and authenticated at the Her-

International Journal of Endocrinology and Metabolism

www.SID.ir
 Antidiabetic action of Syzygium Cumini Bark 99

and Use of Laboratory Animals’ prepared by observed after each drug or vehicle admini-
the National Academy of Sciences and pub- stration. No noticeable adverse effect (i.e.,
lished by the National Institutes of Health respiratory distress, abnormal locomotion and
(NIH). catalepsy) was observed in any animals after
Induction of experimental diabetes: the drug administration. Throughout the ex-
Rats were rendered diabetic by a single in- perimental period, the body weight, food and
traperitoneal injection of freshly prepared fluid intake were monitored. At the end of 45
streptozotocin (45 mg/kg body weight) in 0.1 days, all the animals were killed by decapita-
M citrate buffer (pH 4.5) in a volume of 1 tion (Pentobarbitone sodium) anesthesia (60
ml/kg body weight.41,42 Normal rats received mg/kg body weight). Blood was collected in
1 ml citrate buffer as vehicle. The animals heparin-coated tubes and centrifuged at 1,000
were allowed to drink 5% glucose solution g for 15 min at 4°C.
overnight to overcome the drug-induced hy- Determination of blood glucose and urine
poglycaemia. After 48 h of streptozotocin- sugar:
administration, blood glucose levels were esti- Blood glucose was determined by the O-

D
mated in rats following overnight fasting. toluidine method.44 0.1 ml of blood was pre-
Rats with a blood glucose ranging between cipitated with 1.9 ml of 10% TCA and the
200–300 mg/dL were considered diabetic and precipitate was removed after centrifugation.

SI
used for the experiment. 1 ml of supernatant was mixed with 4 ml of
Experimental design: O-toluidine reagent and kept in a boiling wa-
In the experiment, a total of 30 rats were ter bath for 15 min and cooled. The absorb-
used. The rats were divided into 5 groups of ance was read at 620 nm. Glucose was ex-
6 rats each as follows: Group 1: Normal con- pressed as mg/dL of blood. Urine glucose
of
trol rats administered gum acacia (2%) daily was assessed in fresh urine using glucose in-
by gavage for 45 days. Group 2: Normal rats dicator sticks (Boerhinger Mannheim, Ger-
administered SBEt (300 mg/kg body weight) many).
in aqueous solution daily by gavage for 45 Oral glucose tolerance test:
days. Group 3: Diabetic control rats adminis- OGTT was performed at the end of the ex-
ive

tered gum acacia (2%) daily by gavage for 45 perimental period. Prior to OGTT rats were
days. Group 4: Diabetic rats administered fasted overnight (at least 12 h). 30 min fol-
SBEt (300 mg/kg body weight) in aqueous lowing the various treatment schedules, each
solution daily by gavage for 45 days. Group rat was given an oral glucose load, 2 g/kg
5: Diabetic rats administered reference drug body weight according to Du Vigneaud and
ch

glibenclamide (600 µg/kg body weight) in Karr45 and Al-Awadi et al.46 Blood was with-
aqueous solution daily by gavage for 45 drawn from the retro orbital sinus at -30 min
days.17 (just before the administration of the extract),
Since diabetes is a chronic disorder requir- time 0 (prior to the glucose load), 30, 60 and
Ar

ing long-term therapy, there is a need to as- 120 min after the glucose load. Blood glu-
sess the effect of putative hypoglycae- cose concentrations were estimated using a
mic/antihyperglycaemic agents for a longer glucose oxidase-peroxidase reactive strips
duration. In addition, this application would and a glucometer (Accu-chek, Roche Diag-
be beneficial to reveal the late onset activity nostics, USA).
profile of the agent.43 Therefore an experi- Quantitative determination of plasma in-
ment was planned to assess the effect of sulin and C-peptide:
SBEt for a period of 45 days in streptozoto- Plasma insulin (Awareness Technologies,
cin-induced diabetic rats. Treatment was USA) and C-peptide (Packard, USA) levels
started after 48 h of streptozotocin injection. were determined by the ELISA and RIA
No detectable irritation or restlessness was methods, respectively.

International Journal of Endocrinology and Metabolism

www.SID.ir
100 Ganeasn Saravana and Leelavinothan Pari

Statistical analysis: 15 onwards, decrease in blood glucose was

All data were expressed as mean±S.D of maximum at the end of the 30th day. The
number of experiments. The statistical sig- study was extended further and more signifi-
nificance was evaluated by one-way analysis cant decrease in blood glucose was observed
of variance (ANOVA), using SPSS version on the 45th day. The effect exerted by the ex-
9.5 (SPSS, Cary, NC, USA). Individual com- tract was greater than that of glibenclamide.
parisons were obtained by Duncan’s Multiple Table 2 gives the blood glucose levels of
Range Test (DMRT).47 A p value of < 0.05 normal, diabetic control, SBEt and gliben-
was considered significant. clamide treated animals after oral administra-
tion of glucose. In diabetic animals, blood
Results glucose levels reached peak at 60 min after
Table 1 shows the effect of SBEt on blood glucose administration. Although the glucose
glucose in normal and experimental animals levels started to decline, they remained high
at the end of 15, 30 and 45 days. The level of after 120 min. SBEt and glibenclamide
blood glucose was significantly increased in treated animals showed a significant decrease

D
diabetic rats when compared to normal rats. at 60 min and 120 min after oral glucose ad-
Oral administration of SBEt (300mg/kg body ministration when compared with diabetic
weight) and glibenclamide (600 µg/kg body control animals. At the end of 120 min the

SI
weight) to diabetic rats significantly de- blood glucose reached to near normal levels
creased the blood glucose. In the SBEt in diabetic rats treated with SBEt. Normal
treated groups, although a significant anti-
hyperglycaemic effect was evident from day
of
Table 1. Effect of SBEt on changes in the levels of blood glucose in normal and experimental rats
Blood glucose (mg/dL)
Group
15 days 30 days 45 days
1. Normal 73.79 ± 4.97a 74.98 ± 5.24a 76.05 ± 4.92a
2. Normal + SBEt (300 mg/kg) 72.47 ± 5.01a 68.60 ± 4.01b 65.50 ± 3.65b
ive

3. Diabetic control 245.25 ± 20.35b 259.45 ± 17.99c 268.10 ± 19.25c

4. Diabetic + SBEt (300 mg/kg) 181.29 ± 16.21c 93.65 ± 6.12d 84.30 ± 4.25d
5. Diabetic + Glibenclamide (600µg/kg) 190.56 ± 17.85d 112.56 ± 6.68e 95.00 ± 5.28e
Values are given as mean ± S.D from six rats in each group
ch

Values not sharing a common superscript letter differ significantly at p<0.05 (DMRT)

Table 2. Effect of SBEt on oral glucose tolerance test in normal and experimental rats
Group Blood glucose levels (mg/dL)
Ar

0 min + 30 min + 60 min + 90 min + 120 min

1. Normal 77.61±2.59a 169.20±4.01a 143.09±4.07a 104.20±3.40a 85.92±2.08a
2. Normal + SBEt (300 73.90±2.68b 162.21±3.17b 129.15±4.01b 94.81±3.11b 77.91±2.16b
mg/kg)
3.Diabetic control 265.81±14.65c 319.52±16.21c 369.08±18.19c 343.05±18.32c 316.03±18.03c
4. Diabetic + SBEt 85.90±2.47d 179.34±6.01d 152.28±5.23d 115.03±4.20d 93.94±3.17d
(300 mg/kg)
5. Diabetic + Gliben- 95.93±3.26e 193.47±6.18e 176.04±6.02e 131.08±5.21e 110.01±4.10e
clamide (600 µg/kg)
Values are given as mean ± SD from six rats in each group
Values not sharing a common superscript letter differ significantly at p<0.05 (DMRT)

International Journal of Endocrinology and Metabolism

www.SID.ir
 Antidiabetic action of Syzygium Cumini Bark 101

Table 3. Effect of SBEt on changes in body weight, plasma C-peptide, insulin, and urine sugar of nor-
mal and experimental rats
Changes in body weight
Plasma insulin Plasma C- Urine
Group (g)
(µU/mL) peptide (pmol/L) sugar
Initial Final
1. Normal 179.50±6.98 195.65±6.25a 14.58±0.72a 270.23±13.50a Nil
2. Normal + SBEt (300 182.65±7.12 192.70±5.99a 16.29±0.87b 289.95±14.35b Nil
mg/kg)
3. Diabetic control 184.62±7.17 152.32±5.49b 5.01±0.29c 167.68±8.50c +++
4. Diabetic + SBEt (300 180.40±6.01 195.42±5.65a 10.29±0.59d 236.50±11.87d Nil
mg/kg)
5. Diabetic + Glibencla- 181.61±4.98 193.10±6.14a 9.23±0.46d 230.23±12.10d Trace
mide (600 µg/kg)
Values are given as mean ± S.D from six rats in each group.
Values not sharing a common superscript letter differ significantly at p<0.05 (DMRT)

D
+++ - indicates more than 2% sugar.

SI
rats treated with SBEt also showed signifi- from synthetic or plant sources for the treat-
cant decrease in blood glucose at the 120 min ment of diabetes.48,49 In the present study, the
interval. The effect of SBEt was more pro- aqueous extract of S. cumini bark was inves-
nounced when compared with glibenclamide. tigated for its antidiabetic activity in diabetic
of
Table 3 illustrates the effect of SBEt on rats.
plasma insulin, C-peptide, urine sugar and Animal models of diabetes are increasingly
body weight in normal and experimental being used for pathophysiology and pharma-
animals. The levels of plasma insulin and C- cological studies of diabetes mellitus. Advan-
ive

peptide were significantly decreased whereas tages of animal studies in the examination of
the level of urine sugar was significantly in- alternative medicines and their efficacy in-
creased in diabetic rats when compared with clude the ability to define experimental con-
normal rats. Administration of SBEt and ditions more tightly and to undertake more
glibenclamide to diabetic rats significantly detailed studies of the biologic effects of the
ch

reversed all these changes to near normal agents being used.50 Streptozotocin-induced
levels. Body weights were also significantly hyperglycaemia in rodents is considered to be
reduced in diabetic rats when compared to a good experimental model since it is less
normal rats while the extract significantly toxic than other chemical agents inducing
prevented a decrease in the SBEt treated diabetes. The mechanisms by which strepto-
Ar

animals. zotocin brings about its diabetic state include

selective destruction of pancreatic insulin se-
Discussion creting β-cells, which make cells less active
The world is facing an explosive increase and lead to poor glucose utilization by tis-
in the incidence of diabetes mellitus and cost- sues.51,52
effective complementary therapies are needed. In our study, the intraperitoneal administra-
Although insulin has become one of the most tion of streptozotocin to normal rats effec-
important therapeutic agents known to medi- tively induced diabetes as reflected by glyco-
cine, there is a continuing effort to find insu- suria, hyperglycaemia, hypoinsulinaemia and
lin substitutes, secretagogues, or sensitizers body weight loss. SBEt treatment showed

International Journal of Endocrinology and Metabolism

www.SID.ir
102 Ganeasn Saravana and Leelavinothan Pari

significant hypoglycaemic and antihypergly- lin from the pancreas. As previously de-
caemic effects. The experimental results in- scribed, the streptozotocin treatment reduces
dicated that SBEt exhibited a potent blood insulin secretion by the pancreas through se-
glucose lowering property both in normal and lective destruction of β-cells in the pancreatic
diabetic rats. The capacity of SBEt to de- islets. Perhaps the SBEt treatment could play
crease the elevated blood glucose level to a critical role in repairing the damage of the
normal glycaemic level is an essential trigger pancreatic β-cells and promoting insulin syn-
for the liver to revert to its normal homeosta- thesis, 25 thereby lowering the level of
sis during experimental diabetes. Significant plasma glucose. At this juncture, Achrekar et
reduction of blood glucose in rats treated al.58 reported that water extract of pulp of S.
with SBEt confirms previous reports demon- cumini stimulates release of insulin both in in
strating the hypoglycaemic and antihypergly- vivo and in vitro studies. Bansal et al.59 re-
caemic effects of S. cumini bark in normal ported that the increase in plasma insulin
and diabetic rabbits.53 Our findings also agree brought about by seeds of S. cumini may be
with the recent studies of Villasenor and attributed to proinsulin to insulin conver-

D
Lamadrid54 indicating that the blood glucose sions, possibly by pancreatic cathapsin B,
lowering effect of S. cumini bark extract in and/or its secretion. Diabetics have greater
oral glucose fed hyperglycaemic mice occurs insulinase activity (a proteolytic enzyme that

SI
within 30 min from the onset of S. cumini involves in the conversion of proinsulin to
bark extract treatment. insulin) than non-diabetics.58 The inhibition
Induction of diabetes with streptozotocin is of insulinase activity from the liver and kid-
associated with the characteristic loss of body ney (which are the main sites for insulin ex-
weight, which is due to increased muscle traction) by extract of S. cumini, which has
wasting and due to loss of tissue proteins.55
of
been reported,58 points to an extrapancreatic
Diabetic rats treated with the plant extract mechanism of action also.
showed significant gain in body weight as Phytochemical examinations of this plant
compared to the diabetic control, which may have indicated the presence of flavonoids and
be due to its protective effect in controlling other polyphenolics such as acetyl oleanolic
ive

muscle wasting (i.e. reversal of gluconeo- acid, tannin, gallic acid, ellagic acid, quercetin,
genesis and glycogenolysis) and may also be isoquercetin, kaempferol, myricetin, flavonol
due to the improvement in insulin secretion glycoside, triterpenoids, saponins and antho-
and glycaemic control. cyanin in different concentrations.19-23 Most
Optimal pancreatic β-cell function is essen- of these compounds isolated from different
ch

tial for the regulation of glucose homeostasis plants have previously been suggested to be
in both humans and animals and its impair- the active antidiabetic ingredients of various
ment leads to the development of diabetes.56 plant remedies. These natural compounds
Insulin and C-peptide are the products of the could act separately or synergistically to
Ar

enzymatic cleavage of proinsulin and se- cause the hypoglycaemic effect.60 For in-
creted into the circulation in equimolar con- stance, flavonoids are reported to regenerate
centrations. The measurement of both C- the damaged pancreatic β-cells in diabetic
peptide and insulin levels have been reported animals.61 Vessal et al.62 suggested that
to be a valuable indices of insulin secretion quercetin supplementation promoting regen-
than insulin alone.57 In the present study, eration of the pancreatic islets and increasing
treatment with SBEt showed significant in- insulin release in streptozotocin-induced dia-
crease in plasma insulin and C-peptide levels betic rats. Sezik et al.43 reported inhibitory ef-
in diabetic rats. These results indirectly indi- fect of some flavonoids on c’AMP-
cate that part of the antihyperglycaemic ac- phosphodiesterase activity that eventually
tivity of this plant is through release of insu-

International Journal of Endocrinology and Metabolism

www.SID.ir
 Antidiabetic action of Syzygium Cumini Bark 103

through stimulation of insulin secretion re- processes are diverse.68 It is likely that this
duces blood glucose concentration. Antho- possibility of diversity in the hypoglycaemic
cyanins, the natural colorants have also been mechanism of the action of drugs may also
shown to stimulate insulin secretion from ro- apply to the aqueous extract of S. cumini
dent pancreatic β-cells in vitro.63 Myricetin, a bark. Thus the antidiabetic effect of SBEt
naturally occurring flavonol, was found to may be exerted through the inhibition of glu-
lower blood glucose through improved glu- cose absorption, increase sensitivity of recep-
cose utilization in diabetic animals.64-65 New tors to insulin, insulinase inhibiting effect,
approaches for the treatment of diabetes are stimulation of β-cells of pancreas to secrete
expected to focus on improving insulin sensi- insulin or stimulation of peripheral tissues
tivity or augmenting glucose-dependent insu- uptake of glucose.
lin secretion or decreasing of insulin resis-
tance. Recently, some natural compounds in- Conclusion
cluding flavonoids have been reported to ac- Overall, it can be concluded that SBEt
tivate peroxisome proliferator-activated re- might possess both pancreatic and extrapan-

D
ceptors (PPARs).66 Polyphenolics such as creatic mechanisms in its antidiabetic action
tannin and saponins from several plant ex- and such apparent dual pancreatic and extra-
tracts have also been shown to reduce blood pancreatic actions of S. cumini bark would be

SI
glucose level through inhibition of α- more advantageous to the existing oral
glucosidase enzymes (α-amylase and su- antidiabetic monotherapy. Further phyto-
crase) from the intestine.6,67 chemical and pharmacological studies are
It is well-known that in diabetes, the sites underway to understand the exact mechanism
and mechanism of pharmacological interven- (s) of action of this plant extract.
of
tion (drugs) in the attendant biochemical

References
ive

1. Joshi SK. Indian diabetes risk score. J Assoc Phy- fect of p-methoxycinnamic acid in normal and
sicians India. 2005; 53: 755-57. streptozotocin-induced diabetic rats. Life Sci 2005;
2. Zimmet P, Alberti KG, Shaw J. Global and societal 78: 406-12.
implications of the diabetes epidemic. Nature 2001; 8. Kamtchouing P, Kahpui SM, Dzeufiet PDD, Te-
414: 782-7. dong L, Asongalem EA, Dimoa T. Anti-diabetic
3. Wild S, Roglic G, Green A, Sicree R, King H. activity of methanol/methylene chloride stem bark
ch

Global prevalence of diabetes: estimates for the extracts of Terminalia superba and Canarium
year 2000 and projections for 2030. Diabetes Care. schweinfurthii on streptozotocin-induced diabetic
2004; 27: 1047-53. rats. J Ethnopharmacol 2006; 104: 306-9.
4. Leduc C, Coonishish J, Haddad P, Cuerrier A. 9. Kim SH, Hyun SH, Choung SY. Anti-diabetic ef-
Plants used by the Cree Nation of Eeyou Istchee fect of cinnamon extract on blood glucose in db/db
Ar

(Quebec, Canada) for the treatment of diabetes: a mice. J Ethnopharmacol 2006; 104: 119-23.
novel approach in quantitative ethnobotany. J Eth- 10. Teixeira CC, Pinto LP, Kessler FHP, Knijnik L,
nopharmacol 2006; 105: 55-63. Pinto CP, Gastaldo GJ, et al. The effect of Sy-
5. Sen S, Kar M, Roy A, Chakraborti AS. Effect of gyzium cumini (L.) skeels on postprandial blood
nonenzymatic glycation on functional and struc- glucose levels in non-diabetic rats and rats with
tural properties of hemoglobin. Biophys Chem streptozotocin-induced diabetes mellitus. J Ethno-
2005; 113: 289-98. pharmacol 1997; 56: 209-13.
6. Tiwari AK, Madhusudana Rao J. Diabetes mellitus 11. Chopra RN. Indigenous Drugs of India. 2nd ed.
and multiple therapeutic approaches of phyto- Calcutta: Dhur; 1958.
chemicals: present status and future prospects. Curr 12. Indira G, Mohan Ram M. Jamun. Fruits. National
Sci 2002; 83: 30-38. Institute of Nutrition. Hyderabad: ICMR; 1992.
7. Adisakwattana S, Roengsamran S, Hsu WH, Yib- 13. Nadkarni AK. Indian Materia Medica. Bombay:
chok-anun S. Mechanisms of antihyperglycemic ef- Popular Prakashan; 1954.

International Journal of Endocrinology and Metabolism

www.SID.ir
104 Ganeasn Saravana and Leelavinothan Pari

14. Warrier PK, Nambiar VPK, Ramankutty C. Indian 29. Sharma SB, Nasir A, Prabhu KM, Murthy PS, Dev
Medicinal Plants. Hyderabad: Orient Longman G. Hypoglycaemic and hypolipidemic effect of
Ltd.; 1996. ethanolic extract of seeds of Eugenia jambolana in
15. Bhandary MJ, Chandrashekar KR, Kaveriappa alloxan-induced diabetic rabbits. J Ethnopharmacol
KM. Medical ethnobotany of the siddis of Uttara 2003; 85: 201-6.
Kannada district, Karnataka, India. J Ethnopharma- 30. Prince PSM, Kamalakkannan N, Menon VP.
col 1995; 47: 149-58. Antidiabetic and antihyperlipidaemic effect of al-
16. Pepato MT, Folgado VBB, Kettelhut IC, Brunetti coholic Syzigium cumini seeds in alloxan induced
IL. Lack of antidiabetic effect of a Eugenia jambo- diabetic albino rats. J Ethnopharmacol 2004; 91:
lana leaf decoction on rat streptozotocin diabetes. 209-13.
Braz J Med Biol Res. 2001; 34: 389-95. 31. Ravi K, Rajasekaranm S, Subramanian S. Anti-
17. Pari L, Saravanan G. Antidiabetic effect of Cogent hyperlipidemic effect of Eugenia jambolana seed
db, a herbal drug in alloxan-induced diabetes melli- kernel on streptozotocin-induced diabetes in rats.
tus. Com Biochem Physiol Part C Pharmacol Toxi- Food Chem Toxicol 2005; 43: 1433-39.
col. 2002; 131: 19-25. 32. Prince PSM, Menon VP, Pari L. Hypoglycemic ac-
18. Mitra SK, Gopumadhavan S, Muralidhar TS, An- tivity of Syzigium cumini seeds: effect on lipid
turlikar SD, Sujatha MB.Effect of D-400, a her- peroxidation in alloxan diabetic rats. J Ethnophar-
bomineral preparation on lipid profile, glycated macol 1998; 61: 1-7.
hemoglobin and glucose tolerance in STZ induced 33. Ravi K, Ramachandran B, Subramanian S. Effect

D
diabetes in rats. Indian J Exp Biol 1995; 33: 798- of Eugenia jambolana seed kernel on antioxidant
800. defense system in streptozotocin-induced diabetes
19. Gupta GS, Sharma DP. Triterpenoid and other con- in rats. Life Sci 2004b; 75: 2717–31.

SI
stituents of Eugenia jambolana leaves. Phytochem- 34. Banerjee A, Dasgupta N, De B. In vitro study of
istry 1974; 13: 2013-4. antioxidant activity of Syzygium cumini fruit. Food
20. Bhatia IS, Bhajaj KL. Chemical constituents of the Chem 2005; 90: 727-33.
seeds and bark of Syzygium cumini. Planta Med 35. Kusumoto IT, Nakabayashi T, Kida H, Miyashiro
1975; 28: 346–52. H, Hattori H, Namba T, et al. Screening of various
21. Rastogi RM, Mehrotra BN. Compendium of Indian plant extracts used in ayurvedic medicine for in-
Medicinal Plants. Lucknow: Central Drug Research hibitory effects on human immunodeficiency virus
of
Institute; 1990. type I (HIV-I) protease. Phytother Res 1995; 12:
22. Mahmoud II, Marzouk MSA, Moharram FA, El- 488-93.
Gindi MR, Hassan AMK. Acylated flavonol gly- 36. Chaudhuri AKN, Pal S, Gomes A, Bhattacharya S.
cosides from Eugenia jambolana leaves. Phyto- Anti-inflammatory and related actions of Syzigium
chemistry 2001; 58: 1239-44. cumini seed extract. Phytother Res 1990; 4: 5-10.
ive

23. Jagetia GC, Baliga MS. Syzygium cumini (Jamun) 37. Muruganandan S, Srinivasan K, Chandra S, Tandan
reduces the radiation-induced DNA damage in the SK, Lal J, Raviprakash V. Anti-inflammatory
cultured human peripheral blood lymphocytes: a activity of Syzygium cumini bark. Fitoterapia
preliminary study. Toxicol Lett 2002; 132: 19-25. 2001; 72: 369-75.
24. Prince PSM, Menon VP, Pari L. Hypoglycemic ac- 38. Bhuiyan MA, Mia MY, Rashid MA. Antibacterial
tivity of Syzigium cumini seeds: effect on lipid principles of the seeds of Eugenia jambolana.
ch

peroxidation in alloxan diabetic rats. J Ethnophar- Bangladesh J Bot 1996; 25: 239-41.
macol 1998; 61: 1–7. 39. Ghosh K, Chakraborty D, Chatterjee GK, Chaud-
25. Schossler DRC, Mazzanti CM, Luz SCA, Filappi huri AKN, Pal M. Studies on anti-inflammatory
A, Prestes D, Silveira AF, et al. Syzygium cumini and antipyretic activities of Syzigium cumini Linn,
and the regeneration of insulin positive cells from seeds. IRCS Med Sci Biochem 1985; 13: 340-1.
Ar

the pancreatic duct. Braz J Vet Res Anim Sci 2004; 40. Chakraborty D, Mahapatra PK, Chaudhuri AKN. A
41: 236-9. neuropsycho-pharmacological study of Syzigium
26. Ravi K, Sivagnanam K, Subramanian S. Anti- cumini. Planta Med 1985; 2:139–43.
diabetic activity of Eugenia jambolana seed kernels 41. Siddique O, Sun Y, Lin JC, Chien YW. Facilitated
on streptozotocin induced diabetic rats. J Med Food transdermal transport of insulin. J Pharm Sci. 1987;
2004; 7: 187-91. 76: 341–45.
27. Sharma SB, Nasir A, Prabhu KM, Murthy PS. An- 42. Adisakwattana S, Roengsamran S, Hsu WH, Yib-
tihyperglycemic effect of the fruit-pulp of Eugenia chok-anun S. Mechanisms of antihyperglycemic ef-
jambolana in experimental diabetes mellitus. J Eth- fect of p-methoxycinnamic acid in normal and
nopharmacol 2006; 104: 367-73. streptozotocin-induced diabetic rats. Life Sci 2005;
28. Prince PSM, Menon VP. Hypolipidaemic effect of 78: 406-12.
Syzigium cumini (Jamun) seeds in alloxan diabetic 43. Sezik E, Aslan M, Yesilada E, Ito S. Hypoglycae-
rats. Med Sci Res 1997; 25: 819-21. mic activity of Gentiana olivieri and isolation of the

International Journal of Endocrinology and Metabolism

www.SID.ir
 Antidiabetic action of Syzygium Cumini Bark 105

active constituent through bioassay-directed frac- determinant of pancreatic β-cell function. Nutr Me-
tionation techniques. Life Sci 2005; 76: 1223-38. tab (Lond) 2005; 2: 1.
44. Sasaki T, Matsy S, Sonae A. Effect of acetic acid 57. Kunt T, Forst T, Pfutzner A, Beyer J, Wahren J.
concentration on the colour reaction in the O- The physiological impact of proinsulin C-peptide.
toluidine boric acid method for blood glucose esti- Pathophysiology 1999; 5: 257–62.
mation. Rinsho Kagaku 1972; 1: 346-53. 58. Achrekar S, Kaklij GS, Pote MS, Kelkar SM. Hy-
45. Du Vigneaud V, Karr WG. Carbohydrates utilisa- poglycemic activity of Eugenia jambolana and Fi-
tion rate of disappearance of D-glucose from the cus bengalensis: mechanism of action. In Vivo
blood. J Biol Chem 1925; 66: 281-300. 1991; 5: 143-7.
46. Al-awadi FW, Khattar MA, Gumaa A. On the 59. Bansal R, Ahmad N, Kidwai JR. Effects of oral
mechanism of the hypoglycemic effect of a plant administration of Eugenia jambolana seeds and
extract. Diabetologia 1985; 28: 432-4. chloropropamide on blood glucose level and pan-
47. Duncan BD. Multiple range tests for correlated and creatic cathepsin B in rat. Indian J Biochem Bio-
heteroscedastic means. Biometrics 1957; 13: 359- phys 1981; 18: 377-81.
64. 60. Maghrani M, Zeggwagh NZ, Lemhadri A, Amraoui
48. Pushparaj PN, Tan CH, Tan BKH. The mechanism ME, Michel JB, Eddouks M. Study of the hypogly-
of hypoglycemic action of the semi-purified frac- caemic activity of Fraxinus excelsior and Silybum
tions of Averrhoa bilimbi in streptozotocin diabetic marianum in an animal model of type 1 diabetes

D
rats. Life Sci 2001; 70: 535-47. mellitus. J Ethnopharmacol 2004; 91: 309-16.
49. Bhandari U, Kanojia R, Pillai KK. Effect of 61. Chakravarthy BK, Gupta S, Gode KD. Functional
ethanolic extract of Zingiber officinale on β-cell regeneration in the islets of pancreas in al-
dyslipidaemia in diabetic rats. J Ethnopharmacol loxan induced diabetic rats by (-) epicetechin. Life

SI
2005; 97: 227-30. Sci 1982; 13: 2693-7.
50. Batey RG, Salmond SJ, Bensoussan A. Comple- 62. Vessal M, Hemmati M, Vasei M. Antidiabetic ef-
mentary and alternative medicine in the treatment fects of quercetin in streptozocin-induced diabetic
of chronic liver disease. Curr Gastroenterol Rep rats. Comp Biochem Physiol C Toxicol Pharmacol
2005; 7:63-70. 2003; 135C: 357-64.
51. Junod A, Lambert AE, Stauffacher W, Renold AE. 63. Jayaprakasam B, Vareed SK, Olson LK, Nair MG.
of
Diabetogenic action of streptozotocin of dose to Insulin secretion by bioactive anthocyanins and an-
metabolic response. J Clin Invest 1969; 48: 2129- thocyanidins present in fruits. J Agric Food Chem
39. 2005; 53: 28-31.
52. Kamtchouing P, Kahpui SM, Dzeufiet PDD, Te- 64. Ong KC, Khoo HE. Effects of myricetin on glyce-
dong L, Asongalem EA, Dimo T. Anti-diabetic ac- mia and glycogen metabolism in diabetic rats. Life
tivity of methanol/methylene chloride stem bark Sci 2000; 67: 1695-705.
ive

extracts of Terminalia superba and Canarium 65. Liu IM, Liou SS, Lan TW, Hsu FL, Cheng JT.
schweinfurthii on streptozotocin-induced diabetic Myricetin as the active principle of Abelmoschus
rats. J Ethnopharmacol 2006; 104: 306-9. moschatus to lower plasma glucose in streptozoto-
53. Ratsimamanga AR, Loiseau A, Ratsimamanga- cin-induced diabetic rats. Planta Med 2005; 71:
Urverg S, Bibal-Prot P. Action of a hypoglycemic 617-21.
agent found in the young bark of Eugenia jambo- 66. Kuroda M, Mimaki Y, Sashida Y, Mae T, Kishida
ch

lania(Myrtacea) on induced hyperglycemia of the H, Nishiyama T, et al. Phenolics with PPAR-γ

rabbit and continuation of its purification. C R ligand-binding activity obtained from licorice
Acad Sci Hebd Sciences Acad Sci D 1973; 277: (Glycyrrhiza uralensis roots) and ameliorative ef-
2219-22. fects of glycyrin on genetically diabetic KK-Ay
54. Villasenor IM, Lamadrid MRA. Comparative anti- mice. Bioorg Med Chem Lett 2003; 13: 4267–72.
Ar

hyperglycemic potentials of medicinal plants. J 67. Emilien G, Maloteaux JM, Ponchon M. Pharma-
Ethnopharmacol 2006; 104: 129-31. cological management of diabetes: recent progress
55. Shirwaikar A, Rajendran K, Kumar DC. Oral and future perspective in daily drug treatment.
antidiabetic activity of Annona squamosa leaf alco- Pharmacol Ther 1999; 81: 37-51.
hol extract in NIDDM rats Pharm Biol. 2004; 42: 68. Marles RJ, Farnsworth NR. Antidiabetic plants and
30-5. their active constituents. Phytomed 1995; 2: 137-9.
56. Fatehi-Hassanabad Z, Chan CB. Transcriptional
regulation of lipid metabolism by fatty acids: a key

International Journal of Endocrinology and Metabolism

www.SID.ir