March 2009.indd

SQU MED J, APRIL 2009, VOL. 9, ISS. 1, PP. 63-69, EPUB 16TH MAR 2009
SUBMITTED - 13TH AUG 08
REVISION REQ. 7TH DEC 08, REVISION RECD. 19TH JAN 09
ACCEPTED - 28TH JAN 09

Study of the Effect of Panax Ginseng versus Gliclazide
on Hyperglycaemia Induced by Dexamethasone in

Experimental Animals
Doa’a A Ibrahim

في اجلليكالزيد بدواء ومقارنته جنسنج باناكس نبات تأثير دراسة
في الديكساميثازون بواسطة احملفز الدم سكر مستوى تخفيض

حيوانات التجارب

ابراهيم انور دعاء

اجلليكالزيد بدواء جنسنج ومقارنتها باناكس نبات باستعمال الديكساميثازون عن الناجت العالي الدم سكر مستوى تخفيض دراسة امللخص: الهدف:
إلى 24 أرنبا ــيم مت تقس (اليمن). صنعاء في العلوم والتكنولوجيا بجامعة األدوية علم ــم قس في ــة الدراس التجارب.الطريقة: متت هذه حيوانات في
بينما مجموعات في ثالث ــكر الس ارتفاع لتحفيز 14 يوما ملدة 10 ملجم/كجم مقدارها فموية بجرعة ــامثازون الديكس دواء أعطي مجموعات. أربع
80 بجرعة اجللبكالزيد ، ودواء 200 ملجم/كجم بجرعة ــنج اجلنس بنبات منها مجموعتني معاجلة متت ضابطة. اموعة الرابعة كمجموعة بقيت
سكر مستوى في تخفيض معتدة إحصائية داللة ذات نتائج أعطى جنسنج باناكس نبات أن ــة ــبوعني. النتائج: أظهرت الدراس ملدة أس ملجم/كجم
. 100 مل) / (154.17±21.18 ملجم إلى ( 100 مل / 215.33±27.67 ملجم (من /كجم 10 ملجم بجرعة ديكساميثازون إعطاء بعد الدم
ودواء جنسنج باناكس نبات بني معتدة إحصائية داللة ذو إحصائيا.اخلالصة: هناك فرق معتد ــكل الوزن بش تخفيض ــنج على جنس نبات عمل كذلك
يعانون الذين مرضى السكر قبل من يستخدم أن ميكن اجلنسنج نبات أن استخالص ميكن النتائج هذه من . والوزن الدم سكر تخفيض في اجلليكالزيد

. األنسولني مستلمات في ويتحسن العمل الوزن يقل حيث ، األنسولني مقاومة من يعانون الذين أو السمنة من

ديكساميثازون. ، سكر الدم جليكالزيد ، زيادة ، باناكس جنسنج الكلمات: نبات مفتاح

Department of Pharmacology, University of Science & Technology, Sana’a, Yemen.

*Email: dr_d_anwar@hotmail.com

ABSTRACT Objectives: To study the effect of panax ginseng versus gliclazide on hyperglycaemia induced by dexamethasone in
experimental animals. Methods: The current study was conducted in the Department of Pharmacology, University of Science &
Technology, Sana’a, Yemen. Twenty-four rabbits were divided to 4 groups. Three of them were administered oral doses of dexametha-
sone (0 mg/kg) for 4 days, one group was kept as a control. Ginseng at dose (200 mg/kg) and gliclazide (80 mg/kg) were adminis-
tered to rabbits with dexamethasone-induced hyperglycaemia. Results: The effects of ginseng and gliclazide on fasting blood sugar
(FBS) and body weight after continuous administration of dexamethasone (0 mg/kg) were measured. Oral administration of ginseng
(200mg/kg) for 2 weeks produced significant (p <0.05) reduction in FBS from 25.33±27.67 mg/dl in the dexamethasone group to
54.7±2.8mg/dl in the ginseng treated group. In addition, ginseng produced significant (p <0.05) reduction in body weight. Conclu-
sion: There was a significant difference between ginseng and gliclazide in reduction of FBS and body weight. From these results, it is
suggested that ginseng could be used in obese diabetic patients or those suffering from insulin resistance as it reduces body weight.

Key words: Panax ginseng; Gliclazide; Hyperglycaemia; Dexamethasone.

C L I N I C A L A N D B A S I C R E S E A R C H

Advances in Knowledge
• Unlike other studies, this study focused on the comparison between herbal and chemical medicines in re-

gard to their efficacy and safety for treatment of chronic diseases like diabetes.

• This study supports the efficacy of panax ginseng as a potent antidiabetic agent, which also produces reduc-
tion in body weight, in experimental animal subjects.

D O A’A A I B R A H I M

PLASMA GLUCOSE IS DERIVED FROM THREE sources: intestinal absorption following diges-tion of dietary carbohydrates, glycogenolysis or
the breakdown of glycogen (polymerised storage form
of glucose) and gluconeogenesis.1 Insulin is a hormone
produced by the pancreas that helps unlock the body’s
cells so that sugar (glucose) from the food can be used
by the cells for energy.2 An increase in plasma glu-
cose concentration is the most important physiologic
regulator of insulin secretion. Glucose metabolism,
initiated by the enzyme glucokinase, which converts
glucose to glucose-6-phosphate, is closely linked to in-
sulin secretion. However, an increase of the adenosine
trriphosphate/adenosine diphosphate (ATP/ADP) ra-
tio results in inhibition of ATP-sensitive K efflux chan-
nels. This causes depolarisation of beta cells and acti-
vation of voltage-sensitive Ca channels. The Ca influx
results in insulin secretion.3 Insulin binds to a receptor
on the cell membrane, allowing the entry into muscle
and fat cells of glucose to form glycogen, fatty acids
to generate triglycerides, and amino acids for protein
synthesis. It is a potent stimulator of growth factors,
including insulin-growth factor 1 (IGF-1). It also in-
hibits catabolic processes such as the breakdown of
glycogen and fat, and decreases gluconeogenesis (the
production of glucose from lactate and amino acids);4
however, if there are any disturbances to the binding of
insulin to the receptors, or of the receptor response to
insulin, there will be reduced insulin activity, or insu-
lin resistance. If insulin is not functioning, there is re-
duced glucose entry into the cells, which is detected by
the pancreas as raised blood sugar (hyperglycaemia).
The pancreatic response is then to produce more insu-
lin, (hyperinsulinaemia) to compensate for the lack of
cellular response to the hyperglycaemia. 5

The most common species of ginseng is Panax
quinquefolius, commonly known as American or
Western ginseng. The most commonly sought part of
the plant is its root. Other characteristics of the wild
or cultivated plant and different shapes of the root
make it more valuable. Traditionally, the best plants
are at least 6 years old. Panax ginseng is known as the
Asian, Korean or Japanese ginseng.6

Ginseng is composed primarily of ginesosides,
also known as panaxosides. Other components of
the plant, isolated for pharmacologic effects, include
a volatile oil, beta-elemine, sterols, flavonoids, pep-
tides, vitamins (B1, B2, B12, panthotenic acid, nico-
tinic acid, and biotin), fats, polyacetylenes, enzymes
and choline. The elements phosphorus, potassium,
calcium, thallium, manganese, iron, copper, zinc and
strontium were detected by screening the compo-
nents of ginseng.7 Several pharmacologic effects have
been noted that vary with dose and duration of treat-
ment. The panaxosides found in the root, are thought
to be the pharmacologically active agents. They have
anticonvulsant, analgaesic, antipsychotic effects and
stress-ulcer preventing action. In addition, they show
antiarrhythmic activity similar to verapamil and amio-
darone. Oral ginseng was found to reduce cholesterol
and triglycerides, decrease platelet adhesiveness, im-
pair coagulation, and increase fibrinolysis in choles-
terol-fed rats.8

Moreover, ginseng decreased fasting blood glucose
and haemoglobin A1C in both diabetic and nondia-
betic patients such that some diabetics were free of
insulin therapy for the duration of the study.9 Some
studies in animals have documented ginseng‘s anti-in-
flammatory and antiviral activities,10 hepatoprotective

• Panax ginseng may be used as a supportive therapy, but should not replace current diabetes medications
like sulfonylurea.

Application to Patient care

• Diabetes is a serious chronic metabolic disease and has significant impact on patient’s lives as well as mak-
ing demands of health care systems.

• Panax ginseng possessed a significant antidiabetic effect as compared with well known sulfonylurea mem-
ber gliclazide in experimental animals.

• Our data, suggest that panax ginseng as a dietary supplement or as medicine may have functional efficacy
in obese diabetic patients or those suffering from insulin resistance as it is considered a potent antioxidant
agent.

S T U D Y O F T H E E F F E C T O F PA N A X G I N S E N G V E R S U S G L I C L A Z I D E O N H Y P E R G LY C A E M I A - I N D U C E D B Y D E X A M E T H A S O N E I N
E X P E R I M E N TA L A N I M A L S

and tumors suppressant effects 11 and its beneficial use
in colon cancer.12,13

Gilclazide is a hypoglycaemic agent of the sulfony-
lurea group. Its hypoglycaemic action is related to an
improvement in insulin secretion from the function-
ing beta-cells of the pancreas.14 Gliclazide is rapidly
absorbed from the gastrointestinal tract and the plas-
ma peak of gliclazide occurs between 4 and 6 hours.
It is highly bound to plasma proteins, about 94%. The
mean elimination half-life approximates 10.4 hours.15
However, gliclazide controls diabetes mellitus of stable,
mild, non-ketosis prone, maturity onset or adult types
which can not be controlled by proper dietary man-
agement and exercise, or when insulin therapy is not
appropriate.16 Recently, it was found that gliclazide in-
hibits ischaemia-induced retinal neovascularisation.17

The side effects of this drug include hypoglycaemic
reactions and, as with other sulfonylurea drugs, mani-
festations of hypoglycaemia including dizziness, lack
of energy, drowsiness, headache and sweating as well
as weakness, nervousness, shakiness and paresthaesia.
Sulfonylurea unfortunately has a tendency to pro-
mote weight gain. This effect is aggravated by insulin
resistance.18

M E T H O D S

This study was conducted in Department of Pharma-
cology, University of Science and Technology, Sana’a,
Yemen between May and June 2008.The following cri-
teria were used to include subjects in the study: adult
male rabbits weighing 1-1.5 kg. The following subjects
were excluded from this study: adult female rabbits in
order to eliminate the influence of the oestrous cycle
and pregnancy on our parameters.

The rabbits were purchased from Yemeni markets,
habituated to the new environment at constant tem-
perature, and fed with a standard chow diet ad libitum

for 1 week for acclimatisation. A total of 24 rabbits
were used in the experiment. After one week’s habitu-
ation period, the animals were divided into 4 groups (6
animals in each group), one group being kept as con-
trol. Both control and experimental groups were main-
tained under the similar experimental conditions. The
control group was given only normal saline, while the
other three groups were given continuous oral admin-
istration of dexamethsone (10mg/kg) for two weeks
for induction of hyperglycaemia (above the human
dose). Daily oral doses of Panax ginseng (200 mg/kg)
or gliclazide (80 mg/kg) were used to treat dexametha-
sone-induced hyperglycaemia in the third and fourth
groups of animals respectively for two weeks.

Blood samples were collected after the end of the
experiment early in the morning when the animals
had been kept fasting over the night. The fasting blood
sugar measurement was done according to the method
of Trinder.19 The body weight was measured regularly
for 14 days.

Data were collected and analysed using the SPSS
(Statistical Package for the Social Sciences) pro-
gramme for data analysis, Version 13. They are shown
as mean ± standard error; ‘n’ indicates the number of
animals used. Statistical analysis was performed with
Student’s t test for unpaired observations. Differences
were considered to be statistically significant when p
was less than 0.05.

R E S U L T S

Administration of dexamethasone (10mg/kg) for 2
weeks produced significant (p <0.05) increase in FBS:

Figure 1: Effect of oral administration of dexam-
ethasone (10 mg/kg) on the mean (mean ± SE) fast-
ing blood sugar in adult male rabbits (n = 6)

300

250

200

150

100

0
Control Dexamethasone

Eff
ec

t
o

f d
ex

am
et

h
as

o
n

e
o

n
b

lo
o

d
s

u
g

ar
(m

g
/d

FBS

*Significant difference as compare with control group at p<0.05
FBS = Fasting blood sugar

Figure 2: Effect of oral administration of ginseng
(200mg/kg) on the average mean (Mean ± SE) fast-
ing blood sugar in dexamethasone induced hyper-
glycaemia in adult male rabbits (n=6)

300

250

200

150

100

0
Dexamethasone Ginseng

Eff
ec

t
o

f d
ex

am
et

h
as

o
n

e
o

n
b

lo
o

d
s

u
g

ar
(m

g
/d

FBS

**Significant difference as compare with dexamethasone-induced
hyperglycaemia group at p<0.05
FBS = Fasting blood sugar

D O A’A A I B R A H I M

142.83 ± 15.77mg/dl in the control group compared to
215.33 ± 27.67mg/dl in the dexamethasone group as
shown in Figure 1.

Oral administration of Panax ginseng (200mg/kg)
for 2 weeks produced a significant (p <0.05) decrease
in FBS: from 215.33 ± 27.67mg/dl, in the dexametha-
sone group to 154.17 ± 21.18mg/dl, in the Panax gin-
seng treated group as shown in Figure 2.

Oral administration of gliclazide (80mg/kg) for
2 weeks produced significant (p <0.05) decrease in
FBS: from 215.33 ± 27.67mg/dl in the dexamethasone
group to 169.33 ± 16.51mg/dl in the gliclazide treated
group as shown in Figure 3.

Oral administration of Panax ginseng (200mg/kg)
produced significant (p <0.05) reduction in FBS (154.17
± 21.18 mg/dl) in the Panax ginseng treated group
compared with the gliclazide treated group(169.33 ±
16.51mg/dl) as shown in Figure 4.

D I S C U S S I O N

The present study showed that continuous oral admin-
istration of ginseng in doses of (200mg/kg) for 2 weeks
produced significant reduction in FBS as compared
with dexamethasone-induced hyperglycaemia in rab-
bits.

Our result was in agreement with Luo and Luo
who found that ginseng attenuates hyperglycaemia in
two ways: first, through enhancing pancreatic beta cell
function and second, by reducing insulin resistance.
This would make ginseng effective in both Type I and
Type II diabetes.20 Other studies showed that ginseng
affects pancreatic beta cells through altering cell me-
tabolism, increasing insulin production and reducing
apoptosis in a dosage dependent manner.21 In addition,
ginseng extracts were able to enhance ATP produc-

tion and in turn increase insulin production, as insulin
deficiency is often linked to a lack of ATP.22, 23Along
with an increase in ATP production, ginseng reduced
mitochondrial protein uncoupling protein 2 (UCP-2),
which negatively regulates insulin secretion.22 How-
ever, another study showed that the insulin secretion-
stimulating activity of ginseng was presumably asso-
ciated with the ATP sensitive K channel. This effect,
however, was almost completely abolished in the pres-
ence of diazoxide (K channel opener) or nifedipine (Ca
channel blocker).24 In addition, compound K (CK),
which is a final metabolite of ginsenosides, shifted
glucose metabolism from hepatic glucose production
to hepatic glucose utilisation in the liver and improved
insulin sensitivity through enhancing plasma adi-
ponectin levels, resulting in over expression of genes
for adipogenesis and glucose transporters in adipose
tissue. All these effects may suggest that ginseng could
be developed as therapeutic tool in Type 2 diabetic pa-
tients with insulin secretion disability and/or insulin
resistance.25 Another study suggests that ginseng may
inhibit cytokine-induced apoptosis in beta cells and,
thus, may contribute via this action to the antidiabetic
influence in Type 1 diabetes.26

Continuous administration of gliclazide in an oral
dose (80mg/kg) for 2 weeks produced significant re-
duction in FBS. Our result is supported by Wangnoo
who found that glicalizide is one of the most fre-
quently used sulfonylurea for the treatment of Type
2 diabetes.27 Its hypoglycaemic action is related to an
improvement in insulin secretion from the function-
ing beta cells of the pancreas. It potentiates the insulin
release and improves the dynamics of insulin. In addi-
tion, antidiabetic sulfonylureas are thought to stimu-
late insulin secretion solely by inhibiting their high-

Figure 3: Effect of oral administration of glicaliz-
ide (80mg/kg) on the average mean (Mean ± SE)
fasting blood sugar in dexamethasone induced
hyperglycaemia in adult male rabbits (n = 6)

300

250

200

150

100

0
GliclazideDexamethasone

Eff
ec

t
o

f g
lic

la
zi

d
e

o
n

b
lo

o
d

s
u

g
ar

(m
g

/d
l)

FBS
FBS

**Significant difference as compare with hyperglycaemic induced group at p<0.05
FBS = Fasting blood sugar

* *

Figure 4: Effect of oral administration of Panax
ginseng (200mg/kg) or gliclazide (80 mg/kg) on the
average mean (mean ± SE) fasting blood sugar in
dexamethasone induced hyperglycaemia in adult
male rabbits (n = 6)

* * *

300

250

200

150

100

0
Gliclazide Ginseng

Eff
ec

t
o

f G
in

se
n

o
n

b
lo

o
d

s
u

g
ar

(m
g

/d
l)

FBS
FBS

**Significant difference as compare with gliclazide treated group at p <0.05
FBS = Fasting blood sugar

affinity ATP-sensitive potassium (K (ATP)) channel
receptors at the plasma membrane of beta-cells. This
normally occurs during glucose stimulation, where
ATP inhibition of plasmalemmal K (ATP) channels
leads to voltage activation of L-type calcium channels
for rapidly switching on and off calcium influx, gov-
erning the duration of insulin secretion.28 In contrast,
another study showed that chronic sulfonylurea treat-
ment in vivo causes loss of insulin secretory capacity
due to beta-cell hyperexcitability, but also revealed
rapid reversibility of this secretory failure, arguing
against beta-cell apoptosis or other cell death induced
by sulfonylureas. These in vivo studies may help to ex-
plain why patients with Type 2 diabetes can show long
term secondary failure to secrete insulin in response
to sulfonylureas, but experience restoration of insulin
secretion after a drug resting period, without perma-
nent damage to beta-cells. 29

In addition, ginseng showed significant (p <0.05)
reduction in total body weight compared with the
dexamethasone and glicalizide groups [Figure 5]. This
effect is controversial owing to its mechanism of ac-
tion. However, this effect may be due to the inhibition
of pancreatic lipase activity.30 However, some studies
showed that sulfonylurea may increase body weight
due to an increase in leptin (an obesity gene product)31

or due to an insulin secretion effect.27

This is a single study with a small number of ani-
mals so these limitations have to be kept in mind when
interpreting the results. Further experimental and
clinical investigations should be done to support the
results of this work.

C O N C L U S I O N

It seems that ginseng is effective as an antidiabetic
agent in experimental animal models. It is more than

likely that ginseng affects not only the pancreas to
increase insulin production, but also other tissue to
utilise insulin as well as decrease insulin resistance
through its various components. There was a sig-
nificant difference between ginseng and gliclazide in
reducing fasting blood sugar and body weight. From
these results, it is suggested that ginseng might be used
in obese diabetic patients or those patients suffering
from insulin resistance as it reduces body weight so
improving insulin receptors.

R E C OM M E N DAT I O N S
This study showed that Panax ginseng may help to re-
duce blood glucose level and improve insulin sensitiv-
ity and hence may have potential use in management
of diabetes mellitus patients with obesity.

It was found that both agents are working by the
same mechanism as they stimulate secretion of in-
sulin from beta cell of pancreas. Expected synergis-
tic hypoglycaemic effect may be resulted if they are
combined together. Panax ginseng should be used
cautiously in patients taking any hypoglycaemic medi-
cations. Drug-drug interactions with digoxin and war-
farin have also been reported.

S O U R C E O F F U N D I N G : University of Science &
Technology, Sana’a, Yemen

C O N FL I C T O F I N T E R E ST : None declared

R E F E R E N C E S

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Figure 5: Effect of continuous oral administration of Panax ginseng (200mg/kg) or gliclazide (80mg/kg) on
average total body weight in adult male rabbits (n = 6)

1.6

1.4

1.2

0.8

0.6

0.4

0.2

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14

Dexamethasone

Gliclazide

Control

Ginseng

*Significant as compared with control at p <0.05
**Significant as compared with dexamethasone induced hyperglycaemia at p <0.05

A
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w

ei
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(g
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)

No. of days

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