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ORIGINAL ARTICLE
Year : 2013  |  Volume : 4  |  Issue : 1  |  Page : 26-32

Lack of the cytochrome P450 3A interaction of methanolic extract of Withania somnifera, Withaferin A, Withanolide A and Withanoside IV


Department of Pharmaceutical Analysis, Shobhaben Pratapbhai Patel, School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, Maharashtra, India

Correspondence Address:
Alice Varghese
Department of Pharmaceutical Analysis, Shobhaben Pratapbhai Patel, School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, Maharashtra
India
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Source of Support: Department of Biotechnology, New Delhi, India., Conflict of Interest: None


DOI: 10.4103/0976-9234.116766

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Aims: Withania somnifera is widely employed as a rejuvenator and expected to promote physical health and increase longevity. The aim of the present research work was to evaluate Cytochrome P450 3A (CYP3A) interaction of Withania somnifera. Materials and Methods: In vitro CYP3A interaction of methanolic extract of Withania somnifera (WS) and its principal phytoconstituents: Withaferin-A (WA), Withanolide-A (WL-A) and Withanoside-IV (WS-IV) were investigated in rat and human liver microsomes. In vivo CYP3A interaction potential was investigated by administering methanolic extract of WS orally at a dose of 500 mg/kg in female Wistar rats. Sildenafil citrate was used to index the activity of CYP3A. Results: IC 50 values of methanolic extract of Withania somnifera, WA, WL-A, WS-IV were found to be 200 μg/ml, >20 μM, >64 μM and >64 μM for CYP3A both in rats and humans, respectively. When sildenafil citrate was orally co-administered with methanolic extract of WS and compared with orally administered sildenafil citrate alone, the area under plasma concentration time (AUC) curve and C max did not significantly differ as compared to the group which received rifampicin orally (positive control). Conclusions: Results suggested that methanolic extract of WS, WA, WL-A, WS-IV showed no in vitro CYP3A inhibition in rats and humans. Methanolic extract of WS did not significantly alter the pharmacokinetics of sildenafil citrate in rats; indicating its safety when co-administered with other drugs that are substrates of CYP3A. Thus the results indicate the lesser likelihood of drug herb interactions when concomitantly administered with CYP3A substrates.


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