EFFECT OF ASHWAGANDHA ON PHARMACOKINETIC AND PHARMACODYNAMIC PARAMETERS OF GLIMEPIRIDE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
Â Objective: The present investigation is aimed to determine the effect of ashwagandha (AG) on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of glimepiride (GP) in diabetic rats. Simultaneously, the effect was also studied in normal rats.
Methods: Diabetes in rats was induced by streptozotocin. The PK parameters are calculated in normal and diabetic rats. PD studies were performed in diabetic rats only.
Results: From the PK results, 2.26-folds of improvement in the oral bioavailability of GP in normal rats were observed when treated with GP in a combination of AG and which is statistically significant (p<0.001). In case of diabetic rats, the oral bioavailability (3.42-folds) of GP was significantly increased when coadministered with AG and was higher (about 33.5%) than the normal rats. Further, the rate of clearance and also the volume of distribution significantly changed in diabetic rats. The blood glucose levels were significantly reduced in GP and AG treated (6.15% reduction) compared to GP alone (5.45% reduction) treated diabetic rats during a period of 24 h were noticed from PD studies. The maximum reduction was observed at 6 h (55.46%) when compared with standard GP treatment (46.06%) in case of GP and AG combination treatment.
Conclusion: Therefore, the results suggestive that, the AG might be advantageous as an adjuvant to GP in an appropriate quantity, and also the dose of GP may need to be adjusted to avoid any complications.
2. Rosskamp R, Wernicke-Panten K, Draeger E. Clinical profile of the novel sulphonylurea glimepiride. Diabetes Res Clin Pract 1996;31 Suppl: S33-42.
3. Manisha M, Priyanjali D, Jayant L, Saroj G, Thomas AD. Drugs used for the treatment of diabetes. J Clin Biochem Nutr 2007;40:163-73.
4. Shivraj N, Chandrashekar M. Pharmacodynamic and pharmacokinetic drug interaction of glimepiride and irbesartan in animal models. Int J Phytopharmacol 2013;4:174-8.
5. Dey L, Anoja SA, Yuan CS. Alternative therapies for Type 2 diabetes. Altern Med Rev 2002;7:45-58.
6. Brazier NC, Levine MA. Drug-herb interaction among commonly used conventional medicines: A compendium for health care professionals. Am J Ther 2003;10:163-9.
7. Weiner MA, Weiner J. Ashwagandha (India ginseng). In: Herbs that Heal. Mill Valley, CA: Quantum Books; 1994. p. 70-2.
8. Bhattacharya SK, Satyan KS, Chakrabarti A. Effect of trasina, an ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats. Indian J Exp Biol 1997;35:297-9.
9. Dhuley JN. Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol 1998;60:173-8.
10. Bhattacharya A, Ramanathan M, Ghosal S, Bhattacharya SK. Effect of Withania somnifera glycowithanolides on iron-induced hepatotoxicity in rats. Phytother Res 2000;14:568-70.
11. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: An experimental study. Phytomedicine 2000;7:463-9.
12. Naidu PS, Singh A, Kulkarni SK. Effect of Withania somnifera root extract on reserpine-induced orofacial dyskinesia and cognitive dysfunction. Phytother Res 2006;20:140-6.
13. Owais M, Sharad KS, Shehbaz A, Saleemuddin M. Antibacterial efficacy of Withania somnifera (ashwagandha) an indigenous medicinal plant against experimental murine salmonellosis. Phytomedicine 2005;12:229-35.
14. Matsuda H, Murakami T, Kishi A, Yoshikawa M. Structures of withanosides I, II, III, IV, V, VI and VII new withanolide glycosides from the roots of Indian Withania somnifera D and inhibitory activity for tachyphylaxis to clonidine in isolated guineapig ileum. Bioorg Med Chem 2001;96:1499-507.
15. Shravan KY, Adukondalu D, Vamshi VY, Bhargavilatha A, Sarangapani M. Effect of ashwagandha and Aloe vera pretreatment on intestinal transport of buspirone across rat intestine. Lat Am J Pharm 2011;30:1005-9.
16. Dahikar PR, Kumar N, Sahni YP. Effect of Withania somnifera (Ashwagandha) on the pharmacokinetics of amikacin: A future antimicrobial polypharmacy. J Drug Metab Toxicol 2013;4:1-6.
17. Sujatha S, Veeresham C. Enhanced bioavailability of glimepiride in the presence of boswellic acids in streptozotocin-induced diabetic rat model. Nat Prod Chem Res 2013;1:1-6.
18. Sujatha S, Rani TS, Veeresham C. Determination of glimepiride in rat serum by RP-HPLC method. Am J Anal Chem 2011;2:160-5.
19. Li Y, Wei Y, Zhang F, Wang D, Wu X. Changes in the pharmacokinetics of glibenclamide in rats with streptozotocin-induced diabetes mellitus. Acta Pharm Sinica B 2012;2:198-204.
20. Kumar KE, Rani PD, Ram KR, Swathi P, Gupta MN. Pharmacodynamic and pharmacokinetic drug interaction of gliclazide and risperidone in animal models. Int J Pharm Pharm Sci 2012;4:659-60.
21. Babu PR, Vanishree S, Sujatha S, Kumar KK. Effect of carvedilol on the pharmacokinetics and pharmacodynamics of glipizide. Int J Pharm Pharm Sci 2012;4:133-8.
22. Jaideep S, Samir CP. Pharmacokinetic changes of fluvoxamine and pioglitazone by drug drug interaction in healthy, diabetic and depressive rats. Int J Pharm Pharm Sci 2013;5:352-5.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.