Amalgamation of <i>in-silico</i>, <i>in-vitro</i> and <i>in-vivo</i> approach to establish glabridin as a potential CYP2E1 inhibitor

CYP2E1 is directly or indirectly involved in the metabolism of ethanol and endogenous fatty acids but it plays a major role bio-activation toxic substances that produce reactive metabolites leading to hepatotoxicity. Therefore, identification inhibitor from bioflavonoids class having useful pharmacological properties has dual benefit regarding avoidance severe food-drug/nutraceutical-drug interaction scope develop phytotherapeutics through an intended pharmacokinetic interaction.In present study, we aimed identify experimental which are unexplored for inhibition till date using in-silico, in-vitro in-vivo approaches.Results inhibitory studies CYP2E1-mediated chlorzoxazone 6-hydroxylation human liver microsomes showed glabridin have highest potential than fisetin, epicatechin, nobiletin, chrysin inhibit enzyme. Mechanistic investigations indicate competitive inhibitor. Molecular docking study results demonstrate strongly interacted with active site Pharmacokinetics substrate mice model indicates significant alteration 6-hydroxychlorzoxazone plasma levels presence glabridin. Further needed confirm at clinical level.Overall, found be