Compounds isolated from Curcuma aromatica Salisb. inhibit human P450 enzymes

Curcuma species (Zingiberaceae) are used as both food and medicine in Asia. Ten sesquiterpenes (1-10) and two curcuminoids (11 and 12) were isolated from the rhizomes of Curcuma aromatica Salisb. and identified. The compounds were evaluated for their ability to inhibit cytochrome P450 (CYP). Among them, the sesquiterpene (4S,5S)-(+)-germacrone-4,5-epoxide (7) inhibited certain subtypes of CYP more potently than or at levels comparable to the curcuminoids curcumin (11) and demethoxycurcumin (12); 7 (IC(50) = 1.0 +/- A 0.2 mu M) > 12 (IC(50) = 7.0 +/- A 1.7 mu M) > 11 (IC(50) = 14.9 +/- A 1.4 mu M) for CYP3A4 inhibition; 12 (IC(50) = 1.4 +/- A 0.2 mu M) > 11 (IC(50) = 6.0 +/- A 1.4 mu M) > 7 (IC(50) = 7.6 +/- A 2.5 mu M) for CYP2C9 inhibition; and 7 (IC(50) = 33.2 +/- A 3.6 mu M) = 12 (IC(50) = 34.0 +/- A 14.2 mu M) > 11 (IC(50) > 100 mu M) for CYP1A2 inhibition. These results suggest the possibility that Curcuma aromatica Salisb. may cause food-drug interactions via cytochrome P450 inhibition by sesquiterpene 7 and curcuminoids 11 and 12.