Abstract
The inhibitory effects of 78 herbal extracts on cytochrome P450 3A4 (CYP3A4) and P450 2D6 (CYP2D6) activity were investigated using human liver microsomes. The incubation mixture contained a methanol soluble fraction prepared from the powder of each herbal water extract (equivalent to 1.65 mg of extract powder per mL). Thirty-one herbal extracts inhibited over 50% of human liver microsomal erythromycin N-demethylation, a marker reaction of CYP3A4 activity. Among the 31 herbal extracts, 8 of them (Angelica Dahurica Root, Cassia Bark, Clove, Incised Notopterygium Rhizome, Moutan Bark, Rhubarb, Sappan Wood, Schisandra Fruit) inhibited N-demethylation by over 90%. Among the herbal extracts examined, the strongest inhibition of CYP3A4 was noted with Sappan Wood, which had an IC50 value of 43 mg/mL. Rhubarb, Schisandra Fruit, Incised Notopterygium Rhizome, and Angelica Dahurica Root had IC50 values of 77, 127, 144, and 185 μg/mL, respectively. Further, 28 of the herbal extracts inhibited over 50% of human liver microsomal dextromethorphan O-demethylation, which is a marker of CYP2D6 activity. Among the 28 herbal extracts, 13 (Cassia Bark, Clove, Coptis Rhizome, Ephedra Herb, Gambir Plant, Incised Notopterygium Rhizome, Magnolia Bark, Moutan Bark, Phellodendron Bark, Rhubarb, Sappan Wood, Sinomenium Stem, Zanthoxylum Fruit) inhibited O-demethylation by over 90%. The strongest inhibition of CYP2D6 was noted with Phellodendron Bark, which had an IC50 value of 4 μg/mL. Coptis Rhizome, Sinomenium Stem, Sappan Wood, and Rhubarb showed IC50 values of 14, 40, 52, and 64 μg/mL, respectively. These results indicate that many herbal extracts have an inhibitory effect on CYP3A4 and CYP2D6.
