INVESTIGATION OF CYP1A INTERACTION POTENTIAL OF WITHANIA SOMNIFERA IN RAT AND HUMAN LIVER MICROSOMES
Keywords:
Withania somnifera, CYP1A interaction, Phenacetin, Human liver microsomes, Pharmacokinetics, Herb-drug interactionAbstract
Objective: The aim of this study was to investigate CYP1A interaction of crude extracts (ethanolic, methanolic, hydromethanolic & aqueous) of Withania somnifera and its principal phytoconstituents (withaferin-A and withanolide-A) in rat and human liver microsomes.
Methods: In vitro study were carried out in both rat & human liver microsomes while, in vivo CYP1A interaction potential was investigated by administering the methanolic extract of Withania somnifera orally at a dose of 500 mg/kg in male Wistar rats using probe substrate technique.
Results: The results of this study revealed that IC50 values of all the crude extracts of Withania somnifera and its principal phytoconstituents (withaferin–A & withanolide–A) were found to be >640 µg/ml and >32 µM respectively, for CYP1A enzyme both in rats and humans. However, in vivo pharmacokinetic study of co-administered methanolic extract of Withania somnifera and phenacetin, revealed that the crude extract lead to an approximate 1.5 fold (31%) decrease in AUC 0-24h (p < 0.05). Elimination rate constant (Ke) increased by 2 fold (48%) and half-life (T1/2) decreased by 1.8 fold (43%).
Conclusion: The results of this study suggested that Withania somnifera showed no in vitro CYP1A inhibition in both rats and humans. However, in vivo administration of methanolic extract of Withania somnifera significantly induced CYP1A enzyme & subsequently altered the pharmacokinetics profile of phenacetin in rats; indicating a potential for herb-drug interactions.
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