Inhibition Of CYP3A4, CYP2C9, And CYP2C19 By Aframomum Melegueta Extract And Its Constituents

Aframomum melegueta belonging to the ginger family (Zingiberaceae) grows in tropical parts of Africa. This plant has been used in African traditional medicine for treating several illnesses. The plant is also used as a spice. In addition, antiulcer, cytoprotective, anti-oxidative and antimicrobial activities have been reported in literature. Despite the therapeutic properties and wide spread use of the plant, no literature is available regarding its effects on major drug metabolizing enzymes (CYPs). Many of the clinically relevant herb-drug interactions are caused by inhibition of CYPs. This study was aimed to determine the effects of A. melegueta methanolic extract and its constituents on the activities of major CYPs (3A4, 2D6, 2C9, 1A2, and 2C19). Both reversible and time dependent inhibition (TDI) was determined using recombinant enzymes and specific fluorescent substrates. The methanolic extract showed significant TDI of CYP3A4 (IC₅₀ shift ratio of 3.7) and a potent reversible inhibition of CYP2C9 (IC₅₀ value of 1.4 ± 0.1 µg/mL). Six of the isolated constituents, belonging to the phenyl alkane class, showed TDI of CYP3A4 (IC₅₀ shift ratio > 2). One of them also inhibited CYP2C9 and CYP2C19 strongly (IC₅₀ 2.4 ± 0.2µM and 1.8 ± 0.2 3µM). A weak inhibition of CYP1A2 and no inhibition of CYP2D6 was observed by the extract or the isolated constituents. Our data indicates that the metabolic profile of concomitantly administered drugs that are metabolized by CYP3A4, CYP2C9 or CYP2C19 could be affected by A. melegueta extract and its constituents.

Acknowledgements: This study is supported by The United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58-6408-1-603-04-07 and the Food and Drug Administration "Science Based Authentication of Dietary Supplements" award number 1U01FD004246-05.