Pharmacology & Toxicology Research

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Research Article

EFFECT OF GYMNEMA SYLVESTRE ON THE PHARMACOKINETICS AND

PHARMACODYNAMICS OF 20mg & 40mg GLICLAZIDE IN DIABETIC RATS
1 2 3
Shravan Kumar Dholi , Ramakrishna Raparla , Kannappan
1
Depatment of Pharmacology, JNTUK,Kakinada, A.P-533003, India.
2
Depatment of Pharmaceutics, Vaageswari Institute of Pharmaceutical Sciences, Beside LMD Police Station,
Ramakrishna Colony, Karimnagar, A.P.-505481, India.
3.
Department of Pharmacy, Annamali University, Annamali Nagar, Tamil Nadu-608002. India

Correspondence should be addressed to.Shravan Kumar Dholi

Received July 27, 2015; Accepted August 04, 2015; Published August 08, 2015;

Copyright: © 2015 Shravan Kumar Dholiet al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.

Cite This Article: Dholi, S., Raparla, R., Kannappan. (2015). Effect Of Gymnema Sylvestre On The
Pharmacokinetics And Pharmacodynamics Of 20mg & 40mg Gliclazide In Diabetic Rats. Pharmacology & Toxicology
Research, 2(1).1-10

ABSTRACT

Traditional medicines derived from medicinal plants are used by about 60 per cent world population. Diabetes is an
important human ailment officiating many from various walk of life in different countries including India. It providing to a
major health problem, especially in the rural and subrural areas. Gymnema sylvestre R.Br. (Asclepiadaceae) is a herb
distributed throughout the world. The leaves of the plant are widely used for the treatment of diabetes and as diuretic in
India proprietary medicine. G. sylvestre, an Ayurvedic herb, came to be known as “destroyer of sugar” because, in ancient
times, Ayurvedia physicians observed that chewing a few leaves of G. sylvestre suppressed the taste of sugar. It is used
totally all over India for controlling blood sugar. This study was to determine effect of Gymnema sylvestre on the
pharmacokinetics and pharmacodynamics of Oral hypoglycaemic drugs in streptozotocin induced diabetic rats. Results have
indicated the negative effect of Gymnema Sylvestre on pharmacokinetics but positive effect on pharmacodynamics of oral
hypoglycaemic drugs.

KEYWORDS:Gymnema sylvestre, Pharmacokinetics, pharmacodynamics, Diabetes, Gliclazide.

INTRODUCTION Experimentalstudieshaveshownthatherb-drug
interactionshavebothapharmacokinetic

M
andpharmacodynamicbasis,mostofthatare attributed to the
any medicina l herbal and pharmaceuticaldrugsare induction orinhibitionofhepatic and
intestinalmicrosomalenzymes(primarily cytochromeP450)
therapeuticat onedose andtoxicat another dose. drug transporters [2]. Gliclazideisanoralantihyperglycemic
Interactions between herbal and pharmaceutical drugs can agentusedforthetreatmentofnon-insulin- dependent
increase or decrease the pharmacological or toxicological diabetesmellitus (NIDDM).Itbelongs
effects of either component, herbal drugs are traditionally 1
tothesulfonylureaclassthatactbystimulatingβcellsofthepancr
used to decrease glucose concentrations in diabetic patients eastoreleaseinsulin
[1]could theoretically precipitate hypoglycaemia if taken in [3].Gliclazidebindstotheβcellsulfonylurea receptor
combination with conventional drugs. (SUR1).Thisbinding subsequentlyblockstheATPsensitive
k+channels.Thebindingtoclosingofthe ion channels

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 Pharmacology & Toxicology Research
andleads to aresultingdecreaseink+ ion effluxleadsto VCP/2012/10/6/16}. streptozotocin (Neocare Naturals Pvt.
depolarizationoftheβcells.Thisopens voltage gatedcalcium Ltd, Hyderabad, India).Gymnemasylvestre collected from
channelsintheβislet, Mahadevepur forests India and Plant is authenticated by
thatleadstoexocytosisofinsulincontainingsecretortygranules Dr.E.Narasimha Murthy, Department of Botany,
[4].Oralabsorption ofgliclazideissimilarinpatients and Satavahana University, Karimnagar, Andhra Pradesh.
healthyvolunteers,there isinter subjectvariationintimeto {Specimen Accession Number ENM-100127}.
reachpeakplasmaconcentrations (tmax).Tmax andcmax
areincreasedafterrepeatedgliclazideadministration. Extraction Procedure Of Gymnema Sylvestre
Steadystate
concentrationisachievedafter2daysadministration of40to120 500gm of leaves of Gymnema sylvestre were taken, a
mgofgliclazide.Gliclazidehaslowvolumeofdistribution(13to small amount of dust present as dust was removed by
24L)inbothpatientsandhealthyvolunteers because of shifting through a sieve of mesh number 30.initial
itshighprotein bindingaffinity identification was done by chewing few leaves for a
(85to97%).Theeliminationhalf-life(t1/2)is minute. the mouth rinsed clean with water few grains of
about8.1to20.5hrinhealthyvolunteersandpatients after sugar were placed in mouth and disappearance of sugars
administration of40to120mgorally.Moreover,itsplasma sweetness was felt.1gm powdered material was shaken
clearanceis0.78L/h(13ml/min).Itisextensivelymetabolizedto vigorously with water and examined for more than 30
7metabolitesandexcretedinurinethereforerenalinsufficiency minutes for froth test confirmed presence of saponin
has noinfluencein pharmacokineticof glycosides that is gymnemicacid.500gm of powdered dry
gliclazide[5].Themostnotable effectsarehypoglycaemia; leaf powder was packed soxhlet thimble and extracted
gastrointestinaldisturbancessuchas indigestion, epigastric continuously with 80% of ethanol until the material was
painandchest pain;dermatological reactionssuch completely exhausted. The final product was dark green
asrashandtransientitching;andbiochemicalabnormalitiessuch amorphous powder after evaporation of solvent[11].
as elevated serum creatinine,alkaline
phosphatase,AST,andraisedserum bilirubin.Cerebral Pretreatment
vasodilation,milddisulfiram-likereactionsandlassitude
Albino rats of both gender weight between 180 and 250 g
havebeenreported [6].Gymnemasylvestreis
obtained from National institute of Nutrition, Hyderabad,
usedindifferentsystemsof medicine as a remedy for the
India. These animals were maintained under standard
treatment of diabetes, rheumatism, and cough.[7]. The
conditions in animal house of Vaageswari College of
major phytoconstituents ofGymnemasylvestre are
pharmacy [IAEC number VCP/2012/10/6/16]. Each were
gymnemicacids, gudmarin
kept in elevated wire cages and were provided with high
andsaponins.Gymnemicacid(C43H68O14) isapentacyclic
fat food (carbohydrates: proteins: fat in 42:18:40 ratios) and
triterpenoid andisthemain water ad libitum for a period of 14 days [12].
activephytoconstituentsofGymnema
sylvestre,exhibitingpotentanti- Induction Of Diabetes In Rats By Using 60mg/Kg Of
diabeticactivity[8].Gymnemicacidshow Streptozocin[13]
differentphysiologicalactivities aslower blood glucose and
levels of insulinin thediabeticsubjectsandinhibit intestinal After 2 weeks of feeding with high fat food the rats were
glucose absorption[9].Recent fasted for a period of 18 hours before induction of diabetes,
timeshavewitnessedincreasedincidenceofdiabetesacross the and were injected intra-peritonially with a single dose of
globe,alongwith increasedpopularity ofherbal productsin Streptozocin 60 mg/kg (Sigma–Aldrich, St. Louis, MO,
theinternationalmarket [10]. USA), freshly dissolved in normal saline solution. After
the administration, the rats had free access to food (normal
Rural people are still dependent on indigenous knowledge pellet diet) and water ad libitum. Diabetes in rats was
for health care that are being influenced by culture and identified by moderate polydipsia and marked polyuria.
socioeconomic aspects, providing a cheaper and accessible After 3 days i.e. 72hrs of injection, the fasting blood
alternative to the high cost pharmaceutical remedies. In glucose levels were determined by following glucose
spite of the overwhelming influence and our dependence oxidase/peroxidase GOD/POD method using a
on modern medicine and tremendous advances in synthetic commercial glucose estimation kitwith UV-Visible
drugs, many people still rely on herbs the reason is that, if Spectrophotometer at 505nm. The rats showing fasting
the herbs are used properly they don’t have any side blood glucose more than 150 mg/dL were considered
effects. Hence, the study need to be subjected to diabetic rats and selected for the grouping in
pharmacological studies in order to discover their effect on experimentation.
the patients who are taking the treatment with synthetic
drugs. Study Design
MATERIALS AND METHODS The hyperglycemic rats are divided in to 6 groups 6 animals in
each.
2 Drugs And Chemicals
Group I: Diabetic Control group (0.5% Na.CMC suspension)
Albino rats of either sex weighing between 180 and 250 g
obtained from National institute of Nutrition India. These Group II: Gymnema sylvestre (100 mg/kg)
animals were maintained proper conditions in animal
house of Vaageswari College of pharmacy {IAEC number Group III: Gymnema sylvestre (500 mg/kg)

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Group IV: Gliclazide (40 mg/kg) Statistical Analysis

GroupV: Combination of Gliclazide (20mg/kg) + Gymnema All data are expressed as Mean+Sd. For comparison
sylvestre (500 mg/kg). amongst different groups, One-way analysis of variance
(ANOVA) followed by Dunnet test was performed. P
Group VI: Combination of Gliclazide (40 mg/kg) + value fewer than 5% (P <0.05) was considered to be
Gymnema sylvestre (500 mg/kg).[14] statistically significant.Pharmacokinetic data was
calculated by using pk solver software and statistical
PHARMACOKINETIC STUDY IN DIABETIC RATS analysis was done by INSTANT graph pad software.
Single Dose Study (Acute Study) Histopathological Studies
The studies were carried out in diabetic rats (weight After the last blood glucose estimation, the rats were
between 180g and 250g).They were housed in elevated sacrificed and pancreas were excised and subjected to
wire cages with free access to food and water ad libitum. histopathological studies to determine the inflammatory and
The overnight fasted rats were divided in to six different necrotic changes. The tissues were stained using H&E stain
groups (n=6) and the treatment was given as mentioned in and observed under 100× magnifications. [16].
study design. Post- dosing the blood samples were
collected at predetermined intervals of 0,1,2,4,8,12 and
24hr .in hinto micro-centrifugal tubes containing sodium
citrate from retro-orbital sinus under mild ether
anaesthesia. The blood samples were subjected to
centrifugation at 3000 rpm for 10 min and plasma was
stored at -200C for analysis and determination of
pharmacokinetic parameters as ka, ke, t1/2, V/F, CL/F,
Tmax, Cmax, AUC 0-t, AUC 0 - ∞ .

Multiple Dose Study (Chronic Study)

The diabetic rats were divided into 6 different treatment

groups same as mentioned in study design and Daily
treatment was carried for 21 days(3 weeks).Blood samples
were collected from different groups on 0,7,14,21st day
immediately after treatment. Blood samples were collected
in to micro-centrifugal tubes containing sodium citrate
from retro-orbital sinus under, mild ether anaesthesia. The
blood samples were subjected to centrifugation at 3000
rpm for 10 min and plasma was stored at -200 C for
analysis and determination of pharmacokinetic parameters
as absorption rate constant, elimination rate constant, t1/2,
V/F, CL/F, Tmax, Cmax, AUC 0-t, AUC 0 - ∞ .

PHARMACODYNAMIC STUDY IN DIABETIC RATS

Single Dose Study (Acute Study)

Adults albino rats weighing 180-250g with fasting serum

glucose >150 mg/dl are considered as diabetic. The
treatment was given as mentioned in study design.
Different biochemical parameters as serum glucose,
cholesterol, urea concentrations are measured at different
time intervals of 0, 1, 2, 4, 8, 12 and 24hr by using semi
auto analyzer. These values are considered as acute study
values.

Multiple Dose Study (Chronic Study)

The diabetic rats were divided into 6 different treatment

groups same as mentioned in study design and Daily
treatment was carried for 21 days (3 weeks).Different 3
biochemical parameters as glucose, cholesterol, urea
concentrations of the overnight fasted rats were
determined on 0,7,14,21st day using semi auto
analyzer.[15]

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RESULTS & DISCUSSION

Table 1:Blood glucose levels mg/dl (0th,1st ,2nd,4th,8th, 12th and 24th Hour) after oral administration of Gymnema
sylvestre, Gliclazide and combination of Gliclazide and Gymnema sylvestre in diabetic rats (n=6).

BLOOD GLUCOSE LEVELS (mg/dL)

DIABETIC G S (DOSE) GLICLAZIDE GLICLAZIDE + G S (DOSE)

CONTROL (DOSE)

TREATMENT/Hours vehicle 100mg/kg 500mg/kg 40mg/kg 20mg/kg 40mg/kg

+500mg/kg +500mg/kg

0th Hour 402.2±11.6 411.2±10.4* 390.8±6.5* 386.11±8.13* 381.08±6.15* 378.24±6.73*

BLOOD GLUCOSE
LEVELS

1st Hour 463.6±9.8 409.6±1.20* 387.19±9.3* 380.09±9.05* 371.81±4.28* 356.93±5.66*

BLOOD GLUCOSE
LEVELS

2nd Hour 464.1±9.3 349.2±12.9* 379.11±8.6* 375.13±4.51* 365.15±6.19* 344.08±9.03*

BLOOD GLUCOSE
LEVELS

4th Hour 429.6±7.9 337.4±13.4* 365.26±4.8* 346.88±9.08* 340.86±5.68* 331.99±6.16*

BLOOD GLUCOSE
LEVELS

8th Hour 440.1±8.4 298.2±4.5* 274.91±8.7* 261.81±1.35* 249.81±11.2* 240.18±8.28*

BLOOD GLUCOSE
LEVELS

12th Hour 414.7±9.2 314.6±8.5* 294.7±5.5* 258.36±8.11* 245.81±8.24* 236.91±9.16*

BLOOD GLUCOSE
LEVELS

th
24 Hour 415.8±11.2 323.4±9.6* 301.6±3.4* 264.18±10.16* 251.05±10.61* 241.18±8.11*
BLOOD GLUCOSE
LEVELS

Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) G S-Gymnema sylvetsre
n - number of animals used.
4

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Table 2:Blood cholesterol levels mg/dl (0th,1st ,2nd,4th,8th, 12th and 24th Hour) after oral administration of Gymnema
sylvestre, Gliclazide and combination of Gliclazide and Gymnema sylvestre in diabetic rats (n=6).

BLOOD CHOLESTEROL LEVELS (mg/dL)

DIABETIC G S (DOSE) GLICLAZIDE GLICLAZIDE + G S (DOSE)

CONTROL (DOSE)

TREATMENT/Hours vehicle 100mg/kg 500mg/kg 40mg/kg 20mg/kg 40mg/kg

+500mg/kg +500mg/kg

0th Hour 199.3±12.5 208.2±9.4* 203.5±12.1* 200.81±10.35* 195.94±10.62* 190.16±4.92*

BLOOD
CHOLESTEROL
LEVELS

st
1 Hour 194.2±10.4 200.2±8.4* 195.5±14.2* 183.11±8.04* 179.18±9.16* 176.11±6.45*
BLOOD
CHOLESTEROL
LEVELS

2nd Hour 201.1±6.8 184.6±4.4* 181.6±7.4* 175.05±7.11* 169.15±8.16* 165.99±5.72*

BLOOD
CHOLESTEROL
LEVELS

4th Hour 204.9±12.5 175.2±7.8* 170.2±7.5* 154.24±9.16* 151.18±8.11* 149.03±6.91*

BLOOD
CHOLESTEROL
LEVELS

8th Hour 203.8±8.6 148.1±5.5* 145.9±8.4* 140.66±10.15* 136.15±5.18* 129.66±8.19*

BLOOD
CHOLESTEROL
LEVELS

12th Hour 210.6±9.5 154.9±6.3* 150.4±6.5* 138.48±11.81* 131.61±8.15* 126.48±11.94*

BLOOD
CHOLESTEROL
LEVELS

24th Hour 211.5±7.9 178.7±8.2* 169.6±2.4* 144.88±2.08* 134.84±9.06* 130.11±6.08*

BLOOD
CHOLESTEROL
LEVELS
Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) n - number of animals used
G S - Gymnema sylvetsre .
5

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Table 3:Blood urea levels mg/dl (0th,1st ,2nd,4th,8th, 12th and 24th Hour) after oral administration of Gymnema
sylvestre, Gliclazide and combination of Gliclazide and Gymnema sylvestre in diabetic rats (n=6)

BLOOD UREA LEVELS (mg/dL)

DIABETIC G S (DOSE) GLICLAZIDE GLICLAZIDE + G S (DOSE)

CONTROL (DOSE)

TREATMENT/Hours vehicle 100mg/kg 500mg/kg 40mg/kg 20mg/kg 40mg/kg +500mg/kg

+500mg/kg

0th Hour 63.72±7.5 64.8±5.5* 74.36±4.1* 71.52±5.9* 65.88±6.6* 63.78±4.2*

BLOOD.UREA LEVELS

1st Hour 63.18±2.6 64.72±7.8* 67.5±5.1* 70.38±5.5* 61.02±6.5* 60.48±2.6*

BLOOD UREA
LEVELS

2nd Hour 66.34±9.2 62.02±5.2* 65.24±7.1* 65.18±6.2* 58.78±6.32* 57.7±8.1*

BLOOD UREA
LEVELS

4th Hour 66.96±5.6 59.4±6.2* 57.24±5.4* 54.66±5.2* 56.16±6.35* 55.08±5.5*

BLOOD UREA
LEVELS

8th Hour 68.04±4.5 50.76±6.4* 48.6±5.8* 51.23±71* 45.36±5.4* 43.2±4.4*

BLOOD.UREA
LEVELS

12th Hour 69.12±4.4 54±6.6* 52.38±7.4* 53.26±5.2* 47.52±5.4* 45.36±7.4*

BLOOD UREA
LEVELS

24th Hour 68.24±9.0 61.56±5.2* 59.4±7.5* 56.36±5.1* 55.23±5.4* 52.35±4.4*

BLOOD UREA
LEVELS

Values are given as mean± Standard deviation. *Statistical significance p < 0.05
6 (compared with the control group) G S - Gymnema sylvetsre
n - number of animals used.

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Table 4:Blood glucose levels mg/dL (0th,7th, 14th and 21st day) after oral administration of Gymnema sylvestre, Gliclazide
and combination of Gliclazide and Gymnema sylvestre in diabetic rats (n=6)

BLOOD GLUCOSE LEVELS (mg/dL)

DIABETIC G S (DOSE) GLICLAZIDE GLICLAZIDE+ G S (DOSE)

CONTROL (DOSE)

vehicle 100mg/kg 500mg/kg 40mg/kg 20mg/kg 40mg/kg

TREATMENT/DAYS
+500mg/kg +500mg/kg

ty
0 day 410.2±4.5 419.2±2.2* 395.4±1.2* 390.4±3.1* 386.9±2.3* 370.8±1.3*
BLOOD GLUCOSE LEVELS

7th day 394.2±.2.4 238.1±2.4* 231.±3.1* 217.6±5.2* 211.5±1.34* 202.5±3.3*

BLOOD GLUCOSE LEVELS

14th day 385.8±3.4 180.5±1.5* 150.6±3.4* 120.5±2.6* 111.5±2.4* 106.8±2.4*

BLOOD GLUCOSE LEVELS

21st day 391.7±3.4 130.6±2.4* 121.5±2.5* 101.6±1.6* 98.8±1.4* 91.4±.3.4*

BLOOD GLUCOSE LEVELS
Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) G S - Gymnema sylvetsre
n - number of animals used.

Table 5: Blood cholesterol levels mg/dl (0th,7th, 14th and 21st day) after oral administration of Gymnema sylvestre,
Gliclazide and combination of Gliclazide and Gymnema sylvestre in diabetic rats (n=6).

BLOOD CHOLESTEROL LEVELS (mg/dL)

DIABETIC G S (DOSE) GLICLAZIDE GLICLAZIDE+ G S (DOSE)

CONTROL (DOSE)

TREATMENT/DAYS vehicle 100mg/kg 500mg/kg 40mg/kg 20mg/kg 40mg/kg +500mg/kg

+500mg/kg

ty
0 day 193.7±11.5 188.3±9.5* 182.5±12.2* 186.5±6.3* 181.8±8.4* 175.6±9.2*
BLOOD CHOLESTEROL
LEVELS

7th day 194.8±10.6 105.4±9.6* 102.4±8.4* 103.2±8.1* 94.6±6.6* 90.5±8.6*

BLOOD CHOLESTEROL
LEVELS

14th day 186.2±9.5 86.5±9.23* 84.4±7.8* 77.5±8.24* 72.28±5.8* 69.6±10.8*

BLOOD CHOLESTEROL
LEVELS

st
21 day 191.2±7.8 73.6±10.4* 70.±9.2* 69.2±8.4* 55.1±7.8* 51.2±6.4*
BLOOD CHOLESTEROL 7
LEVELS
Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) G S - Gymnema sylvetsre
n - number of animals used.

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Table 6:Blood urea levels mg/dl (0th,7th, 14th and 21st day) after oral administration of Gymnema sylvestre, Gliclazide and
combination of Gliclazide and Gymnema sylvestre in diabetic rats (n=6).

BLOOD UREA LEVELS (mg/dL)

DIABETIC G S (DOSE) GLICLAZIDE GLICLAZIDE+ G S (DOSE)

CONTROL (DOSE)

TREATMENT/DAYS vehicle 100mg/kg 500mg/kg 40mg/kg 20mg/kg 40mg/kg

+500mg/kg +500mg/kg

th
0 day 71.2±4.83 68.13±8.24* 69.6±6.51* 78.32±4.32* 74.25±4.33* 70.45±3.91*
BLOOD.UREA LEVELS

th
7 day 77.64±9.21 42.25±2.42* 38.12±4.01* 36.24±4.31* 33.21±4.21* 30.23±6.81*
BLOOD.UREA LEVELS

14th day 79.25±7.33 32±8.51* 32.05±6.03* 27.32±5.44* 25.14±9.14* 22.43±8.24*

BLOOD.UREA LEVELS

21st day 70.08±6.25 32.47±9.23* 30.12±8.54* 26.35±10.08* 23.75±9.94* 20.19±8.64*

BLOOD.UREA LEVELS
Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) G S - Gymnema sylvetsre
n - number of animals used.

Table 7:Effect of Gymnema sylvestre on Pharmacokinetic parameters of Single dose administration of Gliclazide in diabetic
rats(n=6)

Pharmacokinetic Units for 40mg/kg GLICLAZIDE + Gymnema sylvestre (DOSE)

parameter Pharmacokinetic of
parameters GLICLAZIDE 20mg/kg+500mg/kg 40mg/kg+500mg/kg

ka h-1 0.91±0.04 0.52±0.11* 0.54±0.31*

-1
ke h 0.21±0.01 0.24±0.05* 0.25±0.08*
t1/2 h 9.19±0.11 9.14±0.83* 9.62±0.14*

V/F (mg/kg)/(μg/ml) 22.25±0.82 28.32±3.14* 34.93±16.26*

CL/F (mg/kg)/(μg/ml)/h 4.59±0.25 6.41±0.31* 8.64±0.61*

Tmax h 2.04±0.08 2.48±0.19* 2.63±0.46*
Cmax μg/ml 1.44±0.02 0.86±0.08* 0.98±0.08*
AUC 0-t μg/ml*h 9.61±0.29 6.88±0.38* 8.98±0.11*
8 AUC 0 - ∞ μg/ml*h 10.64±0.48 7.45±0.36* 9.68±0.35*

Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) G S - Gymnema sylvetsre
n - number of animals use

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Table 8:Effect of Gymnema sylvestre on Pharmacokinetic parameters of Multiple dose administration of Gliclazide in diabetic
rats (n=6)

Pharmacokinetic Units for 40mg/kg of GLICLAZIDE + Gymnema sylvestre (DOSE)

parameter Pharmacokinetic GLICLAZIDE
parameters 20mg/kg+500mg/kg 40mg/kg+500mg/kg

ka h-1 4.31±0.11 3.51±0.44* 3.92±0.25*

-1
ke h 0.46±0.08 0.55±0.09* 0.64±0.03*
t1/2 h 10.4±0.31 9.33±0.61* 9.41±0.88*
V/F (mg/kg)/(μg/ml) 48.18±0.55 35.66±7.81* 55.06±11.43*
CL/F (mg/kg)/(μg/ml)/h 9.02±0.36 8.51±0.99* 10.75±0.83*
Tmax h 3.91±0.06 2.91±0.74* 4.81±0.59*
Cmax μg/ml 3.68±0.09 0.86±0.08* 0.98±0.08*
AUC 0-t μg/ml*h 19.83±0.41 11.52±0.26* 14.63±0.33*
AUC 0 - ∞ μg/ml*h 26.99±0.56 19.81±0.11* 21.53±0.51*
Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) G S - Gymnema sylvetsre
n - number of animals used.

Table 9:Volume of islet cells in pancreas in different groups after multiple dose administration of gliclazide. (n=6).

GROUP Volume of islets (mm3/mm3) / Volume of pancreas (mm3/mm3)

Diabetic Control 0.082 ± 0.004

G S (100 mg/kg, p.o.) 0.195 ± 0.052*

G S (500 mg/kg, p.o.) 0.244 ± 0.007*

Gliclazide (40 mg/kg, p.o.) 0.137 ± 0.009

Gliclazide (20 mg/kg, p.o.) + 0.241 ± 0.036*

G S (500 mg/kg, p.o.)
Gliclazide (40 mg/kg, p.o.) + 0.285 ± 0.043*
G S (500 mg/kg, p.o.)
Values are given as mean± Standard deviation. *Statistical significance p < 0.05
(compared with the control group) G S - Gymnema sylvetsre
n - number of animals used.

The histopathological studies reveal that the combination PHARMACOKINETIC STUDY

of gliclazide (40 mg/kg) and Gymnema sylvestre not only
increased the volume of islets and also recovered partially
destroyed beta cells.
PHARMACODYNAMIC STUDY
The combination of high dose of gliclazide (40 mg/kg) with
500mg/kg Gymnema sylvestre showed maximum
hypoglycaemic action, decrease in serum cholesterol, urea
levels. The influence produced by combination of
gliclazide (20 mg/kg) with Gymnema sylvestre was greater
than the hypoglycaemic action produced by Gymnema
sylvestre (500 mg/kg) alone, but less than gliclazide (40
mg/kg).
The pharmacokinetic study shows that, 27% decreased in
AUC( 0 - ∞) in 500mg/kg of Gymnema sylvestre and
20mg/kg of gliclazide. 47% decrease AUC( 0 - ∞) in
500mg/kg of Gymnema sylvestre and 40mg/kg of
gliclazide. C max was decreased by 34% in 500mg/kg of
Gymnema sylvestre and 20mg/kg of gliclazide., 53% in
500mg/kg of Gymnema sylvestre and 40mg/kg of
gliclazide that was attributed by significant decrease in
absorption rate constant Ka by about 37% in Lower dose of 9
500mg/kg of Gymnema sylvestre and 20mg/kg of
gliclazide, 41% in 500mg/kg of Gymnema sylvestre and
40mg/kg of gliclazide. Significantly increase in clearance
38 % in 500mg/kg of Gymnema sylvestre and 20mg/kg of
gliclazide. 88% in 500mg/kg of Gymnema sylvestre and
PTR 11|Volume 2|Issue 1|2015
 Pharmacology & Toxicology Research
40mg/kg of gliclazide compared to 40mg/kg Gliclazide
group.
CONCLUSION
The interaction of modern medicine with herbs is a
developing area with research activities being carried out
in different parts of the world. The interaction of herbs with
various classes of drugs have been reported and some
drugs such as terfenadine and astemizole from the market
due to such interactions.
The interaction appears to be pharmacokinetic interaction
at absorption, elimination. Gymnema sylvestre inhibits the
absorption of oral hypoglycemics that results in a
significant decrease in the bioavailability of the later and
combination group with a lower dose of oral
hypoglycemics produced increment to the volume of islets
in pancreas compare to individual treatment. Since the
interaction was seen in rats it is likely to occur in humans
leading to decreased activity of oral hypoglycemic that can
need dose adjustments. Hence care must be taken when
the combination is prescribed for clinical benefit in diabetic
patients. The present study warrants next plan to find out
the relevance of the interaction in human beings.
ACKNOWLEDGEMENT
PolarOppositeResponsestoIatrogenicInflammation.Curr
ent DiabetesReviews. 8(6):413-418.
[11] Farzana C., Muhammad H.R. Isolation and
characterization of gymnemic acid from Indigenous
Gymnema sylvestre. 2010;J APP Pharm,3(2):60-65.
[12] Reed, M.J., Meszaros, K., Entes, L.J., Claypool,
M.K., Pinkett, J.G., Gadbois, T.M., Reaven G.M.
(2000) A new rat model of type 2 diabetes: The fat-fed,
streptozotocin- treated rat. Metabolism clinical and
experimental, Vol 49, Issue 11, Pages 1390-1394.
[13] Thulesen, J., Orskov, C., Holst, J.J., Poulsen, S.S.,
(1997) Short term insulin treatment prevents the
diabetogenic action of streptozotocin in rats.
Endocrinology Vol. 138, No. 1 62-68.
[14] Talari, R.,Varshosaz, J., Mostafavi, S.A., Nokhodchi,
A. (June 2010) Gliclazide Microcrystals Prepared by
Two Methods of In Situ Micronization:
Pharmacokinetic Studies in Diabetic and Normal Rats.
AAPS PharmSciTech, Vol. 11, No. 2.
[15] Shavi, G.V., Usha, Y.N., Armugam, K., Ranjan, O.P.,
Ginjupalli, K., Pandey, S., Udupa, N. (2010) Enhanced
dissolution and bioavailability of gliclazide using solid
dispersion techniques. International Journal of Drug
Delivery 2, 49-57.
[16] Navetabhishekam, S.N., Asad, M., Prasad, V.S. (2009)
Pharmacodynamic interaction of Momordica charantia
with rosiglitazone in rats, Chem Biol Interact. 177,247–
253.

I take this privilege and pleasure to acknowledge the

contributions of many individuals who have been
inspirational and supportive throughout my work
undertaken and endowed with the precious knowledge to
see success in my endeavour.

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