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Dr. VIKAS KUMAR
Associate Professor of Pharmacology
Neuropharmacology Laboratory
Department of Pharmaceutics
Institute of Technology
Banaras Hindu University
Varanasi-221 005, U.P., India
Potential Medicinal Plants for
Diabetes and Obesity
Diabetes & Obesity
 Type 2 diabetes is three times more prevalent in obese
individuals than non-overweight persons, and 80% of
people with type 2 diabetes are obese.
 Diabesity, a term denoting clinical association of type 2
diabetes and obesity, represents a substantial economic
burden on health expenditure.
 Insulin resistance is the main culprit in diabesity.
 The molecular link between obesity and insulin resistance
include:
 Insulin: induces receptor down regulation.
 Free fatty acids: impair insulin action.
 Circulating peptides: TNF-α, IL-6 and the "adipokines"
adiponectin and resistin.
2
 The psychological disorders associated with diabetes are
mainly depression, anxiety and memory deficits.
 Diabetes mellitus is accompanied by numerous structural,
biochemical and behavioural alterations of the CNS.
 Several comorbid complications have been described in
rodent models of diabetes including depression and
anxiety.
 Prevalence of depression in diabetic patients are 10-15 % .
 Chances of cognitive dysfunction and dementia are
almost double in diabetic patients.
Diabetes mellitus and its comorbid
neurological complications
3
 Hypericum perforatum: Dried 50 % ethanolic extract (HpE)
standardised by HPLC to contain not less than 3.00 % hyperforin
and 0.30 % hypericines.
 Picrorhiza kurroa: Dried aqueous extract (PkE) standardised
by HPTLC to contain not less than 5.00 % kutkin.
 Quassia amara L.: Dried methanolic extract (QaE)
standardised by HPLC to contain 0.27% of total quassin.
Plant Extracts
4
Oral glucose
tolerance test STZ induced diabetes
GLUT-4 assay Histopathology
Anti-diabetic Activity
5
Figure-1: Effect of HpE, PkE & QaE on oral glucose
tolerance test in normal rats
Values are mean ± SEM, *p<0.05 vs. Normal Control. n=6.
6
Figure-2: Effect of HpE, PkE & QaE on fasting blood glucose
level in diabetic rats
*p<0.05, **p<0.01, ***p<0.001 vs. Nondiabetic Control; †p<0.001 vs. Diabetic Control. n=6.
7
Figure-3: Effect of HpE, PkE & QaE on plasma insulin level
in diabetic rats
*p<0.01 vs. Nondiabetic Control; †p<0.01, ††p<0.001 vs. Diabetic Control. n=6.
8
Table-1: Effect of HpE, PkE & QaE on body weight of
diabetic rats
Group Body weight (g)
Initial body weight Final (14th day)
Normal Control (CMC) 186.00 ± 2.19 190.67 ± 2.06
Diabetic Control (CMC) 183.00 ± 2.37 159 ± 3.52 **
Diabetic + HpE 100 mg/kg 184.00 ± 3.57 170.67 ± 3.5 * †
Diabetic + HpE 200 mg/kg 188.17 ± 3.54 177 ± 4.09 * †
Diabetic + PkE 100 mg/kg 182.25 ± 4.02 180.27 ± 3.08 * †
Diabetic + PkE 200 mg/kg 185.87 ± 4.26 186.00 ± 2.80 ††
Diabetic + QaE 100 mg/kg 184.00 ± 3.57 180.17 ± 2.77 *†
Diabetic + QaE 200 mg/kg 188.17 ± 3.54 192.00 ± 2.80 ††
Diabetic + Glibenclamide 10 mg/kg 185.16 ± 3.8 176.5 ± 3.08 * †
*p< 0.01, **p<0.001 vs. Normal Control; †p<0.01, ††p< 0.001 vs. Diabetic Control. n=6.
9
Table-2: Effect of HpE, PkE & QaE on lipid profile of
diabetic rats
Group TC (mg/dl) TG (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl)
Normal Control 79.53 ± 2.29 46.85 ± 1.47 38.67 ± 0.77 31.48 ± 2.59
Diabetic Control 143.27 ± 6.68 ** 115.31 ± 6.58 ** 24.47 ± 1.43 ** 95.74 ± 7.1 **
Diabetic +
HpE 100 mg/kg
103.8 ± 1.78 ** †† 78.07 ± 3.24** †† 28.18 ± 0.40 ** † 60.00 ± 2.36 ** ††
Diabetic +
HpE 200 mg/kg
85.67 ± 2.69 †† 59.16 ± 1.7 †† 31.74 ± 0.3 ** †† 42.09 ± 3.2 ††
Diabetic +
PkE 100 mg/kg
86.93 ± 1.90 †† 65.41 ± 4.43 ** 27.39 ± 1.44 **† 46.46 ± 2.37 ** ††
Diabetic +
PkE 200 mg/kg
71.42 ± 2.64 †† 56.25 ± 1.62 ** 31.71 ± 1.14 **†† 28.46 ± 2.69 ** ††
Diabetic +
QaE 100 mg/kg
119.59 ± 7.32** † 76.58 ± 6.22 ** 25.76 ± 1.58 ** 78.52 ± 9.27 †
Diabetic +
QaE 200 mg/kg
98.25 ± 4.2 * †† 73.87 ± 4.63 ** 28.90 ± 0.89**† 54.57 ± 4.53 ** ††
Diabetic+
Glibenclamide 10 mg/kg
73.1 ± 2.55 †† 69.37 ± 2.4 * †† 33.94 ± 0.77 * †† 25.28 ± 2.71 ††
*p< 0.01, **p<0.001 vs. Normal Control; †p<0.05, ††p< 0.001 vs. Diabetic Control. n=6. 10
Figure-4: Effect of HpE, PkE & QaE on liver glycogen
content in diabetic rats
*p< 0.01, **p<0.001 vs. Normal Control; †p<0.05, ††p< 0.001 vs. Diabetic Control. n=6.
11
Figure-5: Effect of HpE, PkE & QaE on LPO in diabetic rats
*p< 0.05, ***p<0.001 vs. Normal Control; †p<0.05, ††p< 0.01, †††p< 0.001 vs. Diabetic Control. n=6.
12
Figure-6: Effect of HpE, PkE & QaE on SOD in diabetic rats
*p< 0.05, **p< 0.01, ***p<0.001 vs. Normal Control; †p<0.05, ††p< 0.01, †††p< 0.001 vs. Diabetic Control. n=6.
13
Figure-7: Effect of HpE, PkE & QaE on catalase level in
diabetic rats
*p< 0.05, **p< 0.01, ***p<0.001 vs. Normal Control; †p<0.05, ††p< 0.01, †††p< 0.001 vs. Diabetic Control. n=6.
14
DC NC PkE QaE HpE Glib
GLUT4 - 53KDa
GAPDH - 37KDa
*p<0.01, ** p<0.001 vs. Normal Control; †p<0.001 vs. Diabetic Control. n=6.
Figure-8: Typical immunoblot of GLUT-4 in the total
membrane fraction of skeletal muscle
15
Figure-9: Histopathology of Pancreas (H & E; X100)
Normal Control Diabetic Control Diabetic + Glibenclamide
Diabetic + HpE Diabetic + PkE Diabetic + QaE
16
Figure-10: Histopathology of Liver (H & E; X100)
Normal Control Diabetic + Glibenclamide
Diabetic + HpE Diabetic + PkE Diabetic + QaE
Diabetic Control
17
Figure-11: Histopathology of Kidney (H & E; X100)
Normal Control Diabetic Control Diabetic + Glibenclamide
Diabetic + HpE Diabetic + PkE Diabetic + QaE
18
Hypolipidemic & Anti-
obesity activity
Hypolipidemic
activity
High fat fed
model
Fructose fed
model
19
Table-3: Effect of HpE, PkE & QaE on lipid-parameters in
normal rats
Group Total-C
(mg/dl)
HDL-C
(mg/dl)
LDL-C
(mg/dl)
Triglyceride
(mg/dl)
Control (CMC) 83.98 ± 1.34 31.89 ± 1.21 41.46 ± 2.21 53.10 ± 2.49
HpE 100 mg/kg 73.29 ± 2.10** 35.24 ± 1.56 29.02 ± 2.73** 45.11 ± 2.70
HpE 200 mg/kg 70.51 ± 1.61** 36.64 ± 1.42 25.20 ± 1.60** 43.33 ± 3.67
PkE 100 mg/kg 73.72 ± 2.06** 39.72 ± 1.01* 26.26 ± 2.58** 38.67 ± 2.52*
PkE 200 mg/kg 66.45 ± 2.17*** 42.20 ± 1.76** 17.02 ± 2.27*** 36.22 ± 2.73**
QaE 100 mg/kg 72.65 ± 1.50** 39.67 ± 1.31* 23.42 ± 3.16*** 47.78 ± 2.71
QaE 200 mg/kg 67.31 ± 2.31*** 41.68 ± 2.67** 16.00 ± 0.78*** 44.66 ± 2.91
Clofibrate
100 mg/kg
64.96 ± 2.04*** 42.19 ± 1.09** 15.17 ± 3.25*** 38.00 ± 2.14*
*p<0.05, **p<0.01, ***p<0.001 vs. Normal Control. n=6.
20
Figure-12: Effect of HpE, PkE & QaE on food intake in high
fat fed rats
21
*p<0.01 vs. HFD Control. n=6.
Table-4: Effect of HpE, PkE & QaE on body weight in high
fat fed rats
Group Average body weight (g)
1st day 8th day 15th day 22nd day 30th day
Normal Control
(NPD + CMC)
151.00± 1.44 159.33±1.36 171.67±2.47 180.17±2.41 188.83±1.92
HFD Control
(HFD + CMC)
151.67±1.52 171.50±2.71** 188.17±2.34*** 204.00±2.57*** 226.17±2.915***
HFD +
HpE 100 mg/kg
152.83±1.25 171.00±1.61** 187.83±1.94*** 194.33±1.94** 196.33±1.42††
HFD +
HpE 200 mg/kg
151.50±1.52 170.50±2.19** 187.00±2.46*** 193.83±2.83** 190.33±2.40††
HFD +
PkE 100 mg/kg
150.83±1.35 169.83±1.96** 186.33±2.06*** 193.67±2.08** 197.17±2.33††
HFD +
PkE 200 mg/kg
151.33±1.84 169.00±1.93** 185.67±2.29*** 189.50±2.43*† 193.50±2.19††
HFD +
QaE 100 mg/kg
150.00±1.46 167.83±1.64** 185.67±2.31*** 200.00±2.77*** 219.50±1.84***
HFD +
QaE 200 mg/kg
149.50±1.50 168.83±1.97** 184.50±2.43*** 197.00±2.84*** 218.33±1.99***
*p<0.05, **p<0.01, ***p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. HFD Control. n=6. 22
Table-5: Effect of HpE, PkE & QaE on lipid parameters in
high fat fed rats
Group Total-C
(mg/dl)
HDL-C
(mg/dl)
LDL-C
(mg/dl)
Triglyceride
(mg/dl)
Normal Control
(NPD + CMC)
53.60 ± 2.27 34.65 ± 0.92 33.55 ± 3.07 53.60 ± 2.27
HFD Control
(HFD + CMC)
105.03 ± 4.87*** 24.62 ± 0.79*** 116.49 ± 6.68*** 105.03 ± 4.87***
HFD +
HpE 100 mg/kg
86.27 ± 2.51***†† 28.24 ± 0.89***† 80.72 ± 3.83***††† 86.27 ± 2.51***††
HFD +
HpE 200 mg/kg
80.42 ± 3.61***††† 30.19 ± 0.93**††† 62.85 ± 4.21***††† 80.40 ± 3.61***†††
HFD +
PkE 100 mg/kg
88.78 ± 4.19***† 28.85 ± 0.92***† 70.21 ± 4.54***††† 88.78 ± 4.20***†
HFD +
PkE 200 mg/kg
69.18 ± 3.52**††† 31.89 ± 0.99*††† 55.41 ± 4.34**††† 69.18 ± 3.52**†††
HFD +
QaE 100 mg/kg
97.49 ± 3.33*** 25.83 ± 0.89*** 96.84 ± 5.42***† 97.49 ± 3.33***
HFD +
QaE 200 mg/kg
89.28 ± 3.44***†† 26.38 ± 0.63*** 90.52 ± 4.65***†† 89.28 ± 3.44***††
*p<0.05,**p<0.01,***p<0.001 vs. Normal Control; †p<0.05, ††p<0.01, †††p<0.001 vs. HFD Control. n=6.
23
24
Table-6: Effect of HpE, PkE & QaE on blood glucose and
insulin in high fat fed rats
Group Glucose
(mg/dl)
Plasma Insulin
(µIU/ml)
Normal Control (NPD + CMC) 84.96 ± 3.58 16.61 ± 0.86
HFD Control (HFD + CMC) 130.89 ± 3.70 ** 62.14 ± 2.95 **
HFD + HpE 100 mg/kg 112.15 ± 3.08 ** † 36.47 ± 2.25 ** ††
HFD + HpE 200 mg/kg 98.89 ± 3.01 * †† 28.78 ± 1.53 ** ††
HFD + PkE 100 mg/kg 108.22 ± 2.61** †† 31.22 ± 1.16 ** ††
HFD + PkE 200 mg/kg 93.11 ± 3.54 †† 24.92 ± 1.60 * ††
HFD + QaE 100 mg/kg 119.85 ± 3.84**† 40.34 ± 1.48 ** ††
HFD + QaE 200 mg/kg 107.56 ± 4.03** †† 33.25 ± 1.23 ** ††
*p<0.01, **p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. HFD Control. n=6.
25
Figure-13: Effect of HpE, PkE & QaE on adipose tissue
weight in high fat fed rats
*p<0.01, **p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. HFD Control. n=6.
26
Figure-14: Effect of HpE, PkE & QaE on water intake in
fructose fed rats
*p<0.05, **p<0.01 vs. Normal Control; †p<0.01 vs. Fructose Control. n=6.
27
Table-7: Effect of HpE, PkE & QaE on body weight gain in
fructose fed rats
Group Body weight gain (g)
Normal Control ( drinking water + CMC) 12.33 ± 1.05
Fructose Control (Fructose + CMC) 26.83 ± 2.59*
Fructose + HpE 100 mg/kg 21.00 ± 3.62
Fructose + HpE 200 mg/kg 18.83 ± 2.09
Fructose + PkE 100 mg/kg 18.67 ± 1.69
Fructose + PkE 200 mg/kg 15.17 ± 3.14†
Fructose + QaE 100 mg/kg 21.17 ± 3.12
Fructose + QaE 200 mg/kg 20.17 ± 2.17
*p<0.01 vs. Normal Control; †p<0.05 vs. HFD Control. n=6.
28
Table-8: Effect of HpE, PkE & QaE on lipid parameters in
fructose fed rats
Group Total-C
(mg/dl)
HDL-C
(mg/dl)
LDL-C
(mg/dl)
Triglyceride
(mg/dl)
Normal Control
(Water + CMC)
81.68 ± 2.36 36.21 ± 1.41 35.98 ± 1.65 47.48 ± 3.15
Fructose Control
(Fructose + CMC)
117.12 ± 5.12*** 27.38 ± 1.35 *** 62.04 ± 4.89 ** 138.52 ± 4.88***
Fructose +
HpE 100 mg/kg
106.01 ± 4.35 ** 30.12 ± 0.92* 57.25 ± 5.57 * 93.24 ± 4.12 ***†††
Fructose +
HpE 200 mg/kg
96.99 ± 4.25 † 33.69 ± 1.01†† 47.21 ± 4.84 80.50 ± 4.80 ***†††
Fructose +
PkE 100 mg/kg
96.70 ± 3.91 † 31.98 ± 1.02 † 48.05 ± 4.44 83.33 ± 3.94***†††
Fructose +
PkE 200 mg/kg
84.09 ± 3.88 ††† 35.67 ± 1.14 ††† 35.42 ± 2.98 †† 64.94 ± 3.31 ***†††
Fructose +
QaE 100 mg/kg
110.21 ± 5.78*** 30.71 ± 1.16 * 57.24 ± 5.32* 111.32±3.83***†††
Fructose +
QaE 200 mg/kg
104.21 ± 3.71** 32.73 ± 1.26 † 54.49 ± 4.25* 84.91 ± 3.93 ***†††
*p<0.05,**p<0.01,***p<0.001 vs. Normal Control; †p<0.05, ††p<0.01, †††p<0.001 vs. Fructose Control. n=6.
29
Table-9: Effect of HpE, PkE & QaE on blood glucose and
insulin in fructose fed rats
Group Glucose
(mg/dl)
Plasma Insulin
(µIU/ml)
Normal Control
(Water + CMC)
80.52 ± 3.44 18.05 ± 0.79
Fructose Control
(Fructose + CMC)
149.66 ± 4.49 *** 35.03 ± 1.24 ***
Fructose + HpE 100 mg/kg 125.44 ± 5.70 *** †† 32.32 ± 1.10 ***
Fructose + HpE 200 mg/kg 105.15 ± 3.88 *** †† 30.58 ± 0.83 *** †
Fructose + PkE 100 mg/kg 114.25 ± 4.56 *** †† 27.55 ± 0.91 *** ††
Fructose + PkE 200 mg/kg 92.75 ± 3.78 * †† 22.65 ± 0.88 ** ††
Fructose + QaE 100 mg/kg 121.09 ± 4.01 *** †† 29.63 ± 1.17 *** †
Fructose + QaE 200 mg/kg 107.01 ± 3.81 *** †† 25.62 ± 1.01 *** ††
•p<0.05, **p<0.01, ***p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. Fructose Control. n=6.
Diabetes associated CNS disorders
•Porsolt’s forced swim test
Diabetes
associated
Depression
• Open-field exploration test
• Elevated plus maze test
Diabetes
associated
Anxiety
• Active avoidance test
• Passive avoidance test
Diabetes
associated
memory-
impairment
30
Figure-15 : Effect of HpE, PkE and QaE on forced swim test
•p<0.001 vs. Normal Control; † p<0.001 vs. Diabetic Control. n=6.
31
Table-10: Effect of HpE, PkE & QaE in open field
exploration test
Group Ambulation (N) Rearing
(N)
Self
Grooming(N)
Fecal
dropping(N)
Normal Control
(CMC)
42.67 ± 2.16 13.17 ± 1.01 24.83 ± 1.45 3.50 ± 0.22
Diabetic Control
(CMC)
38.50 ± 2.45 8.83 ± 0.95* 18.16 ± 0.95* 3.83 ± 0.31
Diabetic ±
HpE 100 mg/kg
40.33±2.11 11.5±1.15 20.83±0.86 3.17±0.28
Diabetic ±
HpE 200 mg/kg
45.17±2.27 13.5±1.23† 21.67±1.69† 3.00±0.33
Diabetic ±
PkE 100 mg/kg
40.00 ± 2.77 8.33 ± 0.84* 18.50 ± 0.96 3.67 ± 0.56
Diabetic ±
PkE 200 mg/kg
42.002.79 9.17 ± 0.65 19.17 ± 1.83 4.00 ± 0.58
Diabetic ±
QaE 100 mg/kg
39.17 ± 1.49 8.17 ± 0.75* 17.00 ± 1.86* 3.00 ± 0.26
Diabetic ±
QaE 200 mg/kg
37.67 ± 1.45 8.33 ± 0.84* 16.17 ± 1.40** 3.17 ± 0.61
•p<0.05, ** p<0.01 vs. Normal Control; † p<0.05 vs. Diabetic Control. n=6.
32
Figure-16: Effect of HpE, PkE & QaE in elevated plus maze
test
•p<0.05, *** p<0.001 vs. Normal Control; ††† p<0.001 vs. Diabetic Control. n=6
33
Figure-17: Effect of HpE, PkE & QaE in active avoidance test
***
†
***
†††
*
***
***
***
***
0
10
20
30
40
50
60
70
80
90
%AvoidanceResponse
*p<0.05, ***p<0.001 vs. Normal Control; †p<0.05, †††p<0.001 vs. Diabetic Control. n=6.
34
Figure-18: Effect of HpE, PkE & QaE in passive avoidance
test
***
†
*
†
***
***
*
*** ***
0
5
10
15
20
25
30
35
Acquisition Trial (Day 14) Retention Test (Day 15)
Step-throughLatency(Sec)
Normal Control (CMC) Diabetic Control (CMC)
HpE 100 mg/kg HpE 200 mg/kg
PkE 100 mg/kg PkE 200 mg/kg
QaE 100 mg/kg QaE 200 mg/kg
*p<0.05, ***p<0.001 vs. Normal Control; †p<0.001 vs. Diabetic Control. n=6.
35
Conclusions
 HpE, PkE and QaE demonstrated anti-diabetic activity.
 GLUT4 protein level is significantly increased in skeletal
muscle of PkE and QaE treated diabetic rats indicating
improved insulin mediated glucose transport across the skeletal
muscle membrane.
 All the three extracts have shown hypolipidemic activity in
normal rats.
 HpE and PkE demonstrated anti-obesity activity.
 HpE Showed anxiolytic, antidepressant and nootropic
activity in diabetic animal.
36
Summary
 Present study demonstrated efficacy of Hypericum perforatum in
rodent model of diabetes and obesity. Additionally, HpE also found
effective in diabetes associated depression, anxiety and memory-
impairment; therefore, potentially beneficial for patients suffering
from co-morbid diabetes and CNS disorders
 Observed antidiabetic activity of Picrorhiza kurroa is consonant to
its traditional use as anti-diabetic medication in North- Eastern
Himalayan tribes in India. Picrorhiza kurroa is found to be most
effective in normalising lipid abnormalities induced by diabetes,
high fat diet or fructose feeding, therefore, PkE could be a valuable
alternative therapy for co-morbid condition of diabetes and obesity.
PkE did not show significant improvement in diabetes associated
CNS disorders
37
 Observed anti-hyperglycemic activity of Quassia amara
supports its traditional use as anti-diabetic remedy in Costa
Rica and Guatemala. QaE showed reversal of lipid parameters
in high fat and high fructose fed rats but did not protect weight
gain and accumulation of visceral fat in high fat fed rats. QaE
also did not show any significant improvement in diabetes
associated CNS disorders
 In view of safety data available and wide spread use of these
medicinal plants across the globe, these plants are free from
serious adverse effect unlike various synthetic anti-diabetic
drugs. Therefore, these herbs are potential candidates for
further clinical evaluation
38
Publications
1. Husain GM, Chatterjee SS, Singh PN, Kumar V. Beneficial effect of Hypericum
perforatum on depression and anxiety in a type 2 diabetic rat model. Acta Poloniae
Pharmaceutica – Drug Research (Accepted for Publication, 2011).
2. Kumar V., Husain GM, Chatterjee SS. Search for Plants Against Diabesity : A
comparative preclinical Study. LAP Lambert Academic Publishing AG Co KG,
Germany, 2011. (ISBN 978-3-8443-9087-2).
3. Husain GM, Singh PN, Singh RK, Kumar V. Anti-diabetic activity of standardised
extract of Quassia amara in nicotinamide-streptozotocin-induced diabetic rats.
Phytotherapy Research, 2011 (DOI: 10.1002/ptr.3491).
4. Husain GM, Chatterjee SS, Singh PN, Kumar V. Hypolipidemic and Antiobesity like
Activity of Standardised Extract of Hypericum perforatum L. in Rats. ISRN
Pharmacology 2011. (DOI:10.5402/2011/505247).
5. Husain GM, Singh PN, Kumar V. Beneficial effects of a standardized Hypericum
perforatum extract against experimentally induced hyperglycaemia in rats. Drug
Discoveries & Therapeutics 2009; 3(5):215-220.
6. Husain GM, Singh PN, Kumar V. Antidiabetic activity of standardized extract of
Picrorhiza kurroa in rat model of NIDDM. Drug Discoveries & Therapeutics 2009;
3(3):88-92.
7. Husain GM, Singh PN, Kumar V. Anti-diabetic activity of Indian Hypericum
perforatum L. on alloxan-induced diabetic rats. Pharmacologyonline 2008; 3:889-894.
39
Research Papers
Abstracts in National / International Scientific Conferences
1. Husain GM, Singh PN, Singh RK, Kumar V. Effect of Hypericum perforatum, Picrorhiza kurroa and
Quassia amara on plasma insulin level in nicotinamide-streptozotocin induced diabetic rats. 43rd Annual
Conference of Indian Pharmacological Society & International Conference on Pharmacology and
Translational Research, organized by National Executive Committee 2010-IPS in Association with Food and
Toxicology Research Centre, National Institute of Nutrition, Hyderabad, 2010.
2. Husain GM, Thakur AK, Singh PN, Kumar V. Effect of Picrorhiza kurroa & Quassia amara on high fat diet
induced obesity in rats. Update Ayurveda, organized by Seth GS Medical College & KEM Hospital and TN
Medical College & BYL Nair Ch. Hospital, Mumbai, 2010.
3. Husain GM, Singh PN, Kumar V. Improvement of cognitive functions by Hypericum perforatum in
streptozotocin induced diabetic rats. International Symposium on Brain Aging and Dementia, Department of
Zoology, Banaras Hindu University, Varanasi, 2010.
4. Husain GM, Geed M, Singh PN, Kumar V. Beneficial effect of Hypericum perforatum on high fat diet
induced obesity in rats. 62nd Indian Pharmaceutical Congress, Manipal University, Manipal, 2010.
5. Husain GM, Thakur AK, Singh PN, Kumar V. Lack of antidepressant and anxiolytic activity of Picrorhiza
kurroa and Quassia amara in streptozotocin induced diabetic rats. International Symposium on Brain Aging
and Dementia, Department of Zoology, Banaras Hindu University, Varanasi, 2010.
6. Husain GM, Patel CG, Kumar V. Beneficial effect of Hypericum perforatum on depression and anxiety in
nicotinamide-streptozotocin induced diabetic rats. 61st Indian Pharmaceutical Congress, Ahmedabad, 2009.
7. Husain GM, Singh PN, Kumar V. Anti-diabetic activity of Quassia amara in nicotinamide-streptozotocin-
induced diabetic rats. 42nd Annual Conference of the Indian Pharmacological Society and International
Conference on Integrative & Personalized Medicine, Kolkata, 2009.
8. Husain GM, Singh PN, Kumar V. Hypoglycemic activity of Indian Hypericum perforatum L. on alloxan-
induced diabetic rats. 41st Annual Conference of Indian Pharmacological Society, organized by All India
Institute of Medical Sciences, New Delhi, 2008.
40
 Mr. Gulam Mohammed Husain, Former Ph.D. Scholar.
 Dr. S.S. Chatterjee, Retired Pharmacologist, Dr. Willmar Schwabe, Germany.
 Indian Herbs Ltd., Saharanpur, India.
 Natural Remedies Pvt. Ltd., Bangalore, India.
 Promed Research Centre, Gurgaon, India.
 Dr. R.K. Singh, Assistant Professor, Department of Biochemistry, BHU.
 University Grants Commission, New Delhi, India.
ACKNOWLEDGEMENTS
41
Quassia amara L.
Hypericum perforatum
42
Picrorhiza kurroa

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IDDST-2011 Detailed PPT

  • 1. Dr. VIKAS KUMAR Associate Professor of Pharmacology Neuropharmacology Laboratory Department of Pharmaceutics Institute of Technology Banaras Hindu University Varanasi-221 005, U.P., India Potential Medicinal Plants for Diabetes and Obesity
  • 2. Diabetes & Obesity  Type 2 diabetes is three times more prevalent in obese individuals than non-overweight persons, and 80% of people with type 2 diabetes are obese.  Diabesity, a term denoting clinical association of type 2 diabetes and obesity, represents a substantial economic burden on health expenditure.  Insulin resistance is the main culprit in diabesity.  The molecular link between obesity and insulin resistance include:  Insulin: induces receptor down regulation.  Free fatty acids: impair insulin action.  Circulating peptides: TNF-α, IL-6 and the "adipokines" adiponectin and resistin. 2
  • 3.  The psychological disorders associated with diabetes are mainly depression, anxiety and memory deficits.  Diabetes mellitus is accompanied by numerous structural, biochemical and behavioural alterations of the CNS.  Several comorbid complications have been described in rodent models of diabetes including depression and anxiety.  Prevalence of depression in diabetic patients are 10-15 % .  Chances of cognitive dysfunction and dementia are almost double in diabetic patients. Diabetes mellitus and its comorbid neurological complications 3
  • 4.  Hypericum perforatum: Dried 50 % ethanolic extract (HpE) standardised by HPLC to contain not less than 3.00 % hyperforin and 0.30 % hypericines.  Picrorhiza kurroa: Dried aqueous extract (PkE) standardised by HPTLC to contain not less than 5.00 % kutkin.  Quassia amara L.: Dried methanolic extract (QaE) standardised by HPLC to contain 0.27% of total quassin. Plant Extracts 4
  • 5. Oral glucose tolerance test STZ induced diabetes GLUT-4 assay Histopathology Anti-diabetic Activity 5
  • 6. Figure-1: Effect of HpE, PkE & QaE on oral glucose tolerance test in normal rats Values are mean ± SEM, *p<0.05 vs. Normal Control. n=6. 6
  • 7. Figure-2: Effect of HpE, PkE & QaE on fasting blood glucose level in diabetic rats *p<0.05, **p<0.01, ***p<0.001 vs. Nondiabetic Control; †p<0.001 vs. Diabetic Control. n=6. 7
  • 8. Figure-3: Effect of HpE, PkE & QaE on plasma insulin level in diabetic rats *p<0.01 vs. Nondiabetic Control; †p<0.01, ††p<0.001 vs. Diabetic Control. n=6. 8
  • 9. Table-1: Effect of HpE, PkE & QaE on body weight of diabetic rats Group Body weight (g) Initial body weight Final (14th day) Normal Control (CMC) 186.00 ± 2.19 190.67 ± 2.06 Diabetic Control (CMC) 183.00 ± 2.37 159 ± 3.52 ** Diabetic + HpE 100 mg/kg 184.00 ± 3.57 170.67 ± 3.5 * † Diabetic + HpE 200 mg/kg 188.17 ± 3.54 177 ± 4.09 * † Diabetic + PkE 100 mg/kg 182.25 ± 4.02 180.27 ± 3.08 * † Diabetic + PkE 200 mg/kg 185.87 ± 4.26 186.00 ± 2.80 †† Diabetic + QaE 100 mg/kg 184.00 ± 3.57 180.17 ± 2.77 *† Diabetic + QaE 200 mg/kg 188.17 ± 3.54 192.00 ± 2.80 †† Diabetic + Glibenclamide 10 mg/kg 185.16 ± 3.8 176.5 ± 3.08 * † *p< 0.01, **p<0.001 vs. Normal Control; †p<0.01, ††p< 0.001 vs. Diabetic Control. n=6. 9
  • 10. Table-2: Effect of HpE, PkE & QaE on lipid profile of diabetic rats Group TC (mg/dl) TG (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) Normal Control 79.53 ± 2.29 46.85 ± 1.47 38.67 ± 0.77 31.48 ± 2.59 Diabetic Control 143.27 ± 6.68 ** 115.31 ± 6.58 ** 24.47 ± 1.43 ** 95.74 ± 7.1 ** Diabetic + HpE 100 mg/kg 103.8 ± 1.78 ** †† 78.07 ± 3.24** †† 28.18 ± 0.40 ** † 60.00 ± 2.36 ** †† Diabetic + HpE 200 mg/kg 85.67 ± 2.69 †† 59.16 ± 1.7 †† 31.74 ± 0.3 ** †† 42.09 ± 3.2 †† Diabetic + PkE 100 mg/kg 86.93 ± 1.90 †† 65.41 ± 4.43 ** 27.39 ± 1.44 **† 46.46 ± 2.37 ** †† Diabetic + PkE 200 mg/kg 71.42 ± 2.64 †† 56.25 ± 1.62 ** 31.71 ± 1.14 **†† 28.46 ± 2.69 ** †† Diabetic + QaE 100 mg/kg 119.59 ± 7.32** † 76.58 ± 6.22 ** 25.76 ± 1.58 ** 78.52 ± 9.27 † Diabetic + QaE 200 mg/kg 98.25 ± 4.2 * †† 73.87 ± 4.63 ** 28.90 ± 0.89**† 54.57 ± 4.53 ** †† Diabetic+ Glibenclamide 10 mg/kg 73.1 ± 2.55 †† 69.37 ± 2.4 * †† 33.94 ± 0.77 * †† 25.28 ± 2.71 †† *p< 0.01, **p<0.001 vs. Normal Control; †p<0.05, ††p< 0.001 vs. Diabetic Control. n=6. 10
  • 11. Figure-4: Effect of HpE, PkE & QaE on liver glycogen content in diabetic rats *p< 0.01, **p<0.001 vs. Normal Control; †p<0.05, ††p< 0.001 vs. Diabetic Control. n=6. 11
  • 12. Figure-5: Effect of HpE, PkE & QaE on LPO in diabetic rats *p< 0.05, ***p<0.001 vs. Normal Control; †p<0.05, ††p< 0.01, †††p< 0.001 vs. Diabetic Control. n=6. 12
  • 13. Figure-6: Effect of HpE, PkE & QaE on SOD in diabetic rats *p< 0.05, **p< 0.01, ***p<0.001 vs. Normal Control; †p<0.05, ††p< 0.01, †††p< 0.001 vs. Diabetic Control. n=6. 13
  • 14. Figure-7: Effect of HpE, PkE & QaE on catalase level in diabetic rats *p< 0.05, **p< 0.01, ***p<0.001 vs. Normal Control; †p<0.05, ††p< 0.01, †††p< 0.001 vs. Diabetic Control. n=6. 14
  • 15. DC NC PkE QaE HpE Glib GLUT4 - 53KDa GAPDH - 37KDa *p<0.01, ** p<0.001 vs. Normal Control; †p<0.001 vs. Diabetic Control. n=6. Figure-8: Typical immunoblot of GLUT-4 in the total membrane fraction of skeletal muscle 15
  • 16. Figure-9: Histopathology of Pancreas (H & E; X100) Normal Control Diabetic Control Diabetic + Glibenclamide Diabetic + HpE Diabetic + PkE Diabetic + QaE 16
  • 17. Figure-10: Histopathology of Liver (H & E; X100) Normal Control Diabetic + Glibenclamide Diabetic + HpE Diabetic + PkE Diabetic + QaE Diabetic Control 17
  • 18. Figure-11: Histopathology of Kidney (H & E; X100) Normal Control Diabetic Control Diabetic + Glibenclamide Diabetic + HpE Diabetic + PkE Diabetic + QaE 18
  • 19. Hypolipidemic & Anti- obesity activity Hypolipidemic activity High fat fed model Fructose fed model 19
  • 20. Table-3: Effect of HpE, PkE & QaE on lipid-parameters in normal rats Group Total-C (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) Triglyceride (mg/dl) Control (CMC) 83.98 ± 1.34 31.89 ± 1.21 41.46 ± 2.21 53.10 ± 2.49 HpE 100 mg/kg 73.29 ± 2.10** 35.24 ± 1.56 29.02 ± 2.73** 45.11 ± 2.70 HpE 200 mg/kg 70.51 ± 1.61** 36.64 ± 1.42 25.20 ± 1.60** 43.33 ± 3.67 PkE 100 mg/kg 73.72 ± 2.06** 39.72 ± 1.01* 26.26 ± 2.58** 38.67 ± 2.52* PkE 200 mg/kg 66.45 ± 2.17*** 42.20 ± 1.76** 17.02 ± 2.27*** 36.22 ± 2.73** QaE 100 mg/kg 72.65 ± 1.50** 39.67 ± 1.31* 23.42 ± 3.16*** 47.78 ± 2.71 QaE 200 mg/kg 67.31 ± 2.31*** 41.68 ± 2.67** 16.00 ± 0.78*** 44.66 ± 2.91 Clofibrate 100 mg/kg 64.96 ± 2.04*** 42.19 ± 1.09** 15.17 ± 3.25*** 38.00 ± 2.14* *p<0.05, **p<0.01, ***p<0.001 vs. Normal Control. n=6. 20
  • 21. Figure-12: Effect of HpE, PkE & QaE on food intake in high fat fed rats 21 *p<0.01 vs. HFD Control. n=6.
  • 22. Table-4: Effect of HpE, PkE & QaE on body weight in high fat fed rats Group Average body weight (g) 1st day 8th day 15th day 22nd day 30th day Normal Control (NPD + CMC) 151.00± 1.44 159.33±1.36 171.67±2.47 180.17±2.41 188.83±1.92 HFD Control (HFD + CMC) 151.67±1.52 171.50±2.71** 188.17±2.34*** 204.00±2.57*** 226.17±2.915*** HFD + HpE 100 mg/kg 152.83±1.25 171.00±1.61** 187.83±1.94*** 194.33±1.94** 196.33±1.42†† HFD + HpE 200 mg/kg 151.50±1.52 170.50±2.19** 187.00±2.46*** 193.83±2.83** 190.33±2.40†† HFD + PkE 100 mg/kg 150.83±1.35 169.83±1.96** 186.33±2.06*** 193.67±2.08** 197.17±2.33†† HFD + PkE 200 mg/kg 151.33±1.84 169.00±1.93** 185.67±2.29*** 189.50±2.43*† 193.50±2.19†† HFD + QaE 100 mg/kg 150.00±1.46 167.83±1.64** 185.67±2.31*** 200.00±2.77*** 219.50±1.84*** HFD + QaE 200 mg/kg 149.50±1.50 168.83±1.97** 184.50±2.43*** 197.00±2.84*** 218.33±1.99*** *p<0.05, **p<0.01, ***p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. HFD Control. n=6. 22
  • 23. Table-5: Effect of HpE, PkE & QaE on lipid parameters in high fat fed rats Group Total-C (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) Triglyceride (mg/dl) Normal Control (NPD + CMC) 53.60 ± 2.27 34.65 ± 0.92 33.55 ± 3.07 53.60 ± 2.27 HFD Control (HFD + CMC) 105.03 ± 4.87*** 24.62 ± 0.79*** 116.49 ± 6.68*** 105.03 ± 4.87*** HFD + HpE 100 mg/kg 86.27 ± 2.51***†† 28.24 ± 0.89***† 80.72 ± 3.83***††† 86.27 ± 2.51***†† HFD + HpE 200 mg/kg 80.42 ± 3.61***††† 30.19 ± 0.93**††† 62.85 ± 4.21***††† 80.40 ± 3.61***††† HFD + PkE 100 mg/kg 88.78 ± 4.19***† 28.85 ± 0.92***† 70.21 ± 4.54***††† 88.78 ± 4.20***† HFD + PkE 200 mg/kg 69.18 ± 3.52**††† 31.89 ± 0.99*††† 55.41 ± 4.34**††† 69.18 ± 3.52**††† HFD + QaE 100 mg/kg 97.49 ± 3.33*** 25.83 ± 0.89*** 96.84 ± 5.42***† 97.49 ± 3.33*** HFD + QaE 200 mg/kg 89.28 ± 3.44***†† 26.38 ± 0.63*** 90.52 ± 4.65***†† 89.28 ± 3.44***†† *p<0.05,**p<0.01,***p<0.001 vs. Normal Control; †p<0.05, ††p<0.01, †††p<0.001 vs. HFD Control. n=6. 23
  • 24. 24 Table-6: Effect of HpE, PkE & QaE on blood glucose and insulin in high fat fed rats Group Glucose (mg/dl) Plasma Insulin (µIU/ml) Normal Control (NPD + CMC) 84.96 ± 3.58 16.61 ± 0.86 HFD Control (HFD + CMC) 130.89 ± 3.70 ** 62.14 ± 2.95 ** HFD + HpE 100 mg/kg 112.15 ± 3.08 ** † 36.47 ± 2.25 ** †† HFD + HpE 200 mg/kg 98.89 ± 3.01 * †† 28.78 ± 1.53 ** †† HFD + PkE 100 mg/kg 108.22 ± 2.61** †† 31.22 ± 1.16 ** †† HFD + PkE 200 mg/kg 93.11 ± 3.54 †† 24.92 ± 1.60 * †† HFD + QaE 100 mg/kg 119.85 ± 3.84**† 40.34 ± 1.48 ** †† HFD + QaE 200 mg/kg 107.56 ± 4.03** †† 33.25 ± 1.23 ** †† *p<0.01, **p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. HFD Control. n=6.
  • 25. 25 Figure-13: Effect of HpE, PkE & QaE on adipose tissue weight in high fat fed rats *p<0.01, **p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. HFD Control. n=6.
  • 26. 26 Figure-14: Effect of HpE, PkE & QaE on water intake in fructose fed rats *p<0.05, **p<0.01 vs. Normal Control; †p<0.01 vs. Fructose Control. n=6.
  • 27. 27 Table-7: Effect of HpE, PkE & QaE on body weight gain in fructose fed rats Group Body weight gain (g) Normal Control ( drinking water + CMC) 12.33 ± 1.05 Fructose Control (Fructose + CMC) 26.83 ± 2.59* Fructose + HpE 100 mg/kg 21.00 ± 3.62 Fructose + HpE 200 mg/kg 18.83 ± 2.09 Fructose + PkE 100 mg/kg 18.67 ± 1.69 Fructose + PkE 200 mg/kg 15.17 ± 3.14† Fructose + QaE 100 mg/kg 21.17 ± 3.12 Fructose + QaE 200 mg/kg 20.17 ± 2.17 *p<0.01 vs. Normal Control; †p<0.05 vs. HFD Control. n=6.
  • 28. 28 Table-8: Effect of HpE, PkE & QaE on lipid parameters in fructose fed rats Group Total-C (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) Triglyceride (mg/dl) Normal Control (Water + CMC) 81.68 ± 2.36 36.21 ± 1.41 35.98 ± 1.65 47.48 ± 3.15 Fructose Control (Fructose + CMC) 117.12 ± 5.12*** 27.38 ± 1.35 *** 62.04 ± 4.89 ** 138.52 ± 4.88*** Fructose + HpE 100 mg/kg 106.01 ± 4.35 ** 30.12 ± 0.92* 57.25 ± 5.57 * 93.24 ± 4.12 ***††† Fructose + HpE 200 mg/kg 96.99 ± 4.25 † 33.69 ± 1.01†† 47.21 ± 4.84 80.50 ± 4.80 ***††† Fructose + PkE 100 mg/kg 96.70 ± 3.91 † 31.98 ± 1.02 † 48.05 ± 4.44 83.33 ± 3.94***††† Fructose + PkE 200 mg/kg 84.09 ± 3.88 ††† 35.67 ± 1.14 ††† 35.42 ± 2.98 †† 64.94 ± 3.31 ***††† Fructose + QaE 100 mg/kg 110.21 ± 5.78*** 30.71 ± 1.16 * 57.24 ± 5.32* 111.32±3.83***††† Fructose + QaE 200 mg/kg 104.21 ± 3.71** 32.73 ± 1.26 † 54.49 ± 4.25* 84.91 ± 3.93 ***††† *p<0.05,**p<0.01,***p<0.001 vs. Normal Control; †p<0.05, ††p<0.01, †††p<0.001 vs. Fructose Control. n=6.
  • 29. 29 Table-9: Effect of HpE, PkE & QaE on blood glucose and insulin in fructose fed rats Group Glucose (mg/dl) Plasma Insulin (µIU/ml) Normal Control (Water + CMC) 80.52 ± 3.44 18.05 ± 0.79 Fructose Control (Fructose + CMC) 149.66 ± 4.49 *** 35.03 ± 1.24 *** Fructose + HpE 100 mg/kg 125.44 ± 5.70 *** †† 32.32 ± 1.10 *** Fructose + HpE 200 mg/kg 105.15 ± 3.88 *** †† 30.58 ± 0.83 *** † Fructose + PkE 100 mg/kg 114.25 ± 4.56 *** †† 27.55 ± 0.91 *** †† Fructose + PkE 200 mg/kg 92.75 ± 3.78 * †† 22.65 ± 0.88 ** †† Fructose + QaE 100 mg/kg 121.09 ± 4.01 *** †† 29.63 ± 1.17 *** † Fructose + QaE 200 mg/kg 107.01 ± 3.81 *** †† 25.62 ± 1.01 *** †† •p<0.05, **p<0.01, ***p<0.001 vs. Normal Control; †p<0.01, ††p<0.001 vs. Fructose Control. n=6.
  • 30. Diabetes associated CNS disorders •Porsolt’s forced swim test Diabetes associated Depression • Open-field exploration test • Elevated plus maze test Diabetes associated Anxiety • Active avoidance test • Passive avoidance test Diabetes associated memory- impairment 30
  • 31. Figure-15 : Effect of HpE, PkE and QaE on forced swim test •p<0.001 vs. Normal Control; † p<0.001 vs. Diabetic Control. n=6. 31
  • 32. Table-10: Effect of HpE, PkE & QaE in open field exploration test Group Ambulation (N) Rearing (N) Self Grooming(N) Fecal dropping(N) Normal Control (CMC) 42.67 ± 2.16 13.17 ± 1.01 24.83 ± 1.45 3.50 ± 0.22 Diabetic Control (CMC) 38.50 ± 2.45 8.83 ± 0.95* 18.16 ± 0.95* 3.83 ± 0.31 Diabetic ± HpE 100 mg/kg 40.33±2.11 11.5±1.15 20.83±0.86 3.17±0.28 Diabetic ± HpE 200 mg/kg 45.17±2.27 13.5±1.23† 21.67±1.69† 3.00±0.33 Diabetic ± PkE 100 mg/kg 40.00 ± 2.77 8.33 ± 0.84* 18.50 ± 0.96 3.67 ± 0.56 Diabetic ± PkE 200 mg/kg 42.002.79 9.17 ± 0.65 19.17 ± 1.83 4.00 ± 0.58 Diabetic ± QaE 100 mg/kg 39.17 ± 1.49 8.17 ± 0.75* 17.00 ± 1.86* 3.00 ± 0.26 Diabetic ± QaE 200 mg/kg 37.67 ± 1.45 8.33 ± 0.84* 16.17 ± 1.40** 3.17 ± 0.61 •p<0.05, ** p<0.01 vs. Normal Control; † p<0.05 vs. Diabetic Control. n=6. 32
  • 33. Figure-16: Effect of HpE, PkE & QaE in elevated plus maze test •p<0.05, *** p<0.001 vs. Normal Control; ††† p<0.001 vs. Diabetic Control. n=6 33
  • 34. Figure-17: Effect of HpE, PkE & QaE in active avoidance test *** † *** ††† * *** *** *** *** 0 10 20 30 40 50 60 70 80 90 %AvoidanceResponse *p<0.05, ***p<0.001 vs. Normal Control; †p<0.05, †††p<0.001 vs. Diabetic Control. n=6. 34
  • 35. Figure-18: Effect of HpE, PkE & QaE in passive avoidance test *** † * † *** *** * *** *** 0 5 10 15 20 25 30 35 Acquisition Trial (Day 14) Retention Test (Day 15) Step-throughLatency(Sec) Normal Control (CMC) Diabetic Control (CMC) HpE 100 mg/kg HpE 200 mg/kg PkE 100 mg/kg PkE 200 mg/kg QaE 100 mg/kg QaE 200 mg/kg *p<0.05, ***p<0.001 vs. Normal Control; †p<0.001 vs. Diabetic Control. n=6. 35
  • 36. Conclusions  HpE, PkE and QaE demonstrated anti-diabetic activity.  GLUT4 protein level is significantly increased in skeletal muscle of PkE and QaE treated diabetic rats indicating improved insulin mediated glucose transport across the skeletal muscle membrane.  All the three extracts have shown hypolipidemic activity in normal rats.  HpE and PkE demonstrated anti-obesity activity.  HpE Showed anxiolytic, antidepressant and nootropic activity in diabetic animal. 36
  • 37. Summary  Present study demonstrated efficacy of Hypericum perforatum in rodent model of diabetes and obesity. Additionally, HpE also found effective in diabetes associated depression, anxiety and memory- impairment; therefore, potentially beneficial for patients suffering from co-morbid diabetes and CNS disorders  Observed antidiabetic activity of Picrorhiza kurroa is consonant to its traditional use as anti-diabetic medication in North- Eastern Himalayan tribes in India. Picrorhiza kurroa is found to be most effective in normalising lipid abnormalities induced by diabetes, high fat diet or fructose feeding, therefore, PkE could be a valuable alternative therapy for co-morbid condition of diabetes and obesity. PkE did not show significant improvement in diabetes associated CNS disorders 37
  • 38.  Observed anti-hyperglycemic activity of Quassia amara supports its traditional use as anti-diabetic remedy in Costa Rica and Guatemala. QaE showed reversal of lipid parameters in high fat and high fructose fed rats but did not protect weight gain and accumulation of visceral fat in high fat fed rats. QaE also did not show any significant improvement in diabetes associated CNS disorders  In view of safety data available and wide spread use of these medicinal plants across the globe, these plants are free from serious adverse effect unlike various synthetic anti-diabetic drugs. Therefore, these herbs are potential candidates for further clinical evaluation 38
  • 39. Publications 1. Husain GM, Chatterjee SS, Singh PN, Kumar V. Beneficial effect of Hypericum perforatum on depression and anxiety in a type 2 diabetic rat model. Acta Poloniae Pharmaceutica – Drug Research (Accepted for Publication, 2011). 2. Kumar V., Husain GM, Chatterjee SS. Search for Plants Against Diabesity : A comparative preclinical Study. LAP Lambert Academic Publishing AG Co KG, Germany, 2011. (ISBN 978-3-8443-9087-2). 3. Husain GM, Singh PN, Singh RK, Kumar V. Anti-diabetic activity of standardised extract of Quassia amara in nicotinamide-streptozotocin-induced diabetic rats. Phytotherapy Research, 2011 (DOI: 10.1002/ptr.3491). 4. Husain GM, Chatterjee SS, Singh PN, Kumar V. Hypolipidemic and Antiobesity like Activity of Standardised Extract of Hypericum perforatum L. in Rats. ISRN Pharmacology 2011. (DOI:10.5402/2011/505247). 5. Husain GM, Singh PN, Kumar V. Beneficial effects of a standardized Hypericum perforatum extract against experimentally induced hyperglycaemia in rats. Drug Discoveries & Therapeutics 2009; 3(5):215-220. 6. Husain GM, Singh PN, Kumar V. Antidiabetic activity of standardized extract of Picrorhiza kurroa in rat model of NIDDM. Drug Discoveries & Therapeutics 2009; 3(3):88-92. 7. Husain GM, Singh PN, Kumar V. Anti-diabetic activity of Indian Hypericum perforatum L. on alloxan-induced diabetic rats. Pharmacologyonline 2008; 3:889-894. 39 Research Papers
  • 40. Abstracts in National / International Scientific Conferences 1. Husain GM, Singh PN, Singh RK, Kumar V. Effect of Hypericum perforatum, Picrorhiza kurroa and Quassia amara on plasma insulin level in nicotinamide-streptozotocin induced diabetic rats. 43rd Annual Conference of Indian Pharmacological Society & International Conference on Pharmacology and Translational Research, organized by National Executive Committee 2010-IPS in Association with Food and Toxicology Research Centre, National Institute of Nutrition, Hyderabad, 2010. 2. Husain GM, Thakur AK, Singh PN, Kumar V. Effect of Picrorhiza kurroa & Quassia amara on high fat diet induced obesity in rats. Update Ayurveda, organized by Seth GS Medical College & KEM Hospital and TN Medical College & BYL Nair Ch. Hospital, Mumbai, 2010. 3. Husain GM, Singh PN, Kumar V. Improvement of cognitive functions by Hypericum perforatum in streptozotocin induced diabetic rats. International Symposium on Brain Aging and Dementia, Department of Zoology, Banaras Hindu University, Varanasi, 2010. 4. Husain GM, Geed M, Singh PN, Kumar V. Beneficial effect of Hypericum perforatum on high fat diet induced obesity in rats. 62nd Indian Pharmaceutical Congress, Manipal University, Manipal, 2010. 5. Husain GM, Thakur AK, Singh PN, Kumar V. Lack of antidepressant and anxiolytic activity of Picrorhiza kurroa and Quassia amara in streptozotocin induced diabetic rats. International Symposium on Brain Aging and Dementia, Department of Zoology, Banaras Hindu University, Varanasi, 2010. 6. Husain GM, Patel CG, Kumar V. Beneficial effect of Hypericum perforatum on depression and anxiety in nicotinamide-streptozotocin induced diabetic rats. 61st Indian Pharmaceutical Congress, Ahmedabad, 2009. 7. Husain GM, Singh PN, Kumar V. Anti-diabetic activity of Quassia amara in nicotinamide-streptozotocin- induced diabetic rats. 42nd Annual Conference of the Indian Pharmacological Society and International Conference on Integrative & Personalized Medicine, Kolkata, 2009. 8. Husain GM, Singh PN, Kumar V. Hypoglycemic activity of Indian Hypericum perforatum L. on alloxan- induced diabetic rats. 41st Annual Conference of Indian Pharmacological Society, organized by All India Institute of Medical Sciences, New Delhi, 2008. 40
  • 41.  Mr. Gulam Mohammed Husain, Former Ph.D. Scholar.  Dr. S.S. Chatterjee, Retired Pharmacologist, Dr. Willmar Schwabe, Germany.  Indian Herbs Ltd., Saharanpur, India.  Natural Remedies Pvt. Ltd., Bangalore, India.  Promed Research Centre, Gurgaon, India.  Dr. R.K. Singh, Assistant Professor, Department of Biochemistry, BHU.  University Grants Commission, New Delhi, India. ACKNOWLEDGEMENTS 41
  • 42. Quassia amara L. Hypericum perforatum 42 Picrorhiza kurroa