Pharmaceutical Research & Development   (Track)

CYP3A4 AND CYP2E1 INHIBITORY ACTIVITIES OF APIGENIN DERIVATIVES FROM SAHARIAN PLANTS

Ameddah Souad, Menad Ahmed, Dendouhi Hocine, Said El-Hocini Mahmoud Hilal, Benayache Samir and Benayache Fadila

Faculté des Sciences de la Nature et de la vie, Université Frères Mentouri Constantine, Algérie, Constantine, Algeria

Abstract

The majority of toxic chemicals require metabolic activation by microsomal enzymes with formation of mutagenic and carcinogenic metabolites. The cytochrome (CYP3A4, CYP2E1) activities were involved in metabolic activation of pro-mutagens and tumour-promising activity of various xenobiotic. Their prevention is considered to be important characteristic of chemopreventive compounds. The apigenin derivatives which were isolated from the saharian plant, chrysanthemum fuscatum (using 13C NMR, 1H NMR, SMIE, and HMBC) were investigated for their capability to inhibit in vitro CYP3A4 and CYP2E1 activity. The results revealed that the complex vitexin-amide was the most effective and the consistent inhibitor (80 %) in a dose dependent-manner for both CYP 3A4 and CYP2E1. Vitexin and apigenin were the potent inhibitor of CYP3A4 (60 %) while apigenin failed to inhibit CYP2E1 and needed 20 μM concentrations. The present data seem to suggest that 5-, 7-, 4'- hydroxyl and 8-glucose in apigenin structure associated to the presence of amide might be promising chemoprotective compound against CYP2E1 and CYP3A4 activities.

Keywords: Apigenin derivatives, CYP2E1, CYP3A4.