Research Article Open Access

Influence of Quercetin on Diabetes-Induced Alteration in CYP3A Activity and Bioavailability of Pioglitazone in Rats

Sudhir Niranjan Umathe1, Pankaj Vinod Dixit1, Jignesh Manubhai Vaghasiya1 and Nishant Sudhir Jain2
  • 1 Rashtrasant Tukadoji Maharaj Nagpur University, India
  • 2 Wanadongri, Hingna Road, India

Abstract

Problem statement: Quercetin-a common bioflavonoid, is present in herbal preparations consumed by diabetic patients along with routine anti-diabetic agents. We recently showed that quercetin increases the bioavailability of pioglitazone in non-diabetic rats. Thus, present study investigated whether this pharmacokinetic interaction is also evident in diabetic animals, especially because diabetic subjects have altered gastrointestinal (GI) function and CYP3A activity. Approach: The study was carried out in alloxan-induced (40 mg kg-1, i.v.) diabetic rats. After 2 weeks of diabetes induction, rats were treated for 2 weeks with quercetin (10 mg kg-1, p.o.) or vehicle (5% methyl cellulose, 10 mL kg-1). At the end of 4 weeks, these rats were used to investigate: (1) GI function in terms of gastric emptying and intestinal transit of semisolid barium sulphate meal; (2) CYP3A activity in liver and intestinal microsomes by erythromycin N-demethylase assay; (3) Plasma levels of orally and intravenously administered pioglitazone (10 mg kg-1, p.o.; 5 mg kg-1, i.v.). Results: The results revealed that diabetic rats exhibited: (1) Delayed gastric emptying and intestinal transit; (2) Decreased CYP3A activity and (3) A significant increase in the oral and intravenous AUC0-∞ of pioglitazone as compared to non-diabetic rats. Quercetin treatment prevented the diabetes-induced GI dysfunction, whereas diabetes-induced decrease in CYP3A activity and increased bioavailability of pioglitazone remained unaffected. Conclusion: The results suggested that quercetin attenuated GI dysfunction but did not affect the bioavailability of pioglitazone in diabetic rats contrary to the increase reported in non-diabetic rats. However, the safety of co-joint use of quercetin containing herbs and pioglitazone in clinical practice requires further pharmacokinetic substantiation.

American Journal of Infectious Diseases
Volume 5 No. 2, 2009, 118-125

DOI: https://doi.org/10.3844/ajidsp.2009.118.125

Submitted On: 27 March 2009 Published On: 30 June 2009

How to Cite: Umathe, S. N., Dixit, P. V., Vaghasiya, J. M. & Jain, N. S. (2009). Influence of Quercetin on Diabetes-Induced Alteration in CYP3A Activity and Bioavailability of Pioglitazone in Rats. American Journal of Infectious Diseases, 5(2), 118-125. https://doi.org/10.3844/ajidsp.2009.118.125

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Keywords

  • Herbal medicine
  • alloxan
  • diabetic gastroparesis
  • Erythromycin N demethylase