Inhibition of human P450 enzymes by compounds from Curcuma aromatica Salisb. rhizome extract

A growing number of naturally occurring phytochemicals in foods and herbal supplements have been shown to be substrates or inactivators of P450 enzymes [1]. Curcuma aromatica Salisb. is one of many distributed healthy supplements in Japan recently. We isolated and identified 10 sesquiterpenes and 2 diarylheptanoids from Curcuma aromatica. Above 12 compounds were evaluated on inhibition of human CYP3A4, CYP2D6, CYP2E1, and CYP1A2 using fluorescence assay in vitro. (4S, 5S) – (+) – germacrone 4, 5– expoxide (7), curcumin (11) and demethoxy-curcumin (12) showed inhibitory effects against CYP 3A4 and 2C9. These compounds in particular had inhibitory activity for three substrates (BFC, BQ, and DBF) in the case of CYP3A4. Although coumarins and flavonoids are known to inhibit the human P450s so far, there are few reports that sesquiterpene inhibit CYP3A4 and CYP2C9.

Reference: 1. Ute M. Kent et al. (2002) Drug Metab Dispos. 30:709–715.