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 ± 0.2 μM) > 12 (IC 50 = 7.0 ± 1.7 μM) > 11 (IC 50 = 14.9 ± 1.4 μM) for CYP3A4 inhibition; 12 (IC 50 = 1.4 ± 0.2 μM) > 11 (IC 50 = 6.0 ± 1.4 μM) > 7 (IC 50 = 7.6 ± 2.5 μM) for CYP2C9 inhibition; and 7 (IC 50 = 33.2 ± 3.6 μM) = 12 (IC 50 = 34.0 ± 14.2 μM) > 11 (IC 50 > 100 μM) 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 .