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
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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.
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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.
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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.
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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
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16. Figure-9: Histopathology of Pancreas (H & E; X100)
Normal Control Diabetic Control Diabetic + Glibenclamide
Diabetic + HpE Diabetic + PkE Diabetic + QaE
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17. Figure-10: Histopathology of Liver (H & E; X100)
Normal Control Diabetic + Glibenclamide
Diabetic + HpE Diabetic + PkE Diabetic + QaE
Diabetic Control
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18. Figure-11: Histopathology of Kidney (H & E; X100)
Normal Control Diabetic Control Diabetic + Glibenclamide
Diabetic + HpE Diabetic + PkE Diabetic + QaE
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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.
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
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34. Figure-17: Effect of HpE, PkE & QaE in active avoidance test
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†††
*
***
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***
***
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.
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35. Figure-18: Effect of HpE, PkE & QaE in passive avoidance
test
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*
†
***
***
*
*** ***
0
5
10
15
20
25
30
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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.
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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.
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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
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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
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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.
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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.
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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
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