In vitro inhibition of huanglian [Rhizoma coptidis (L.)] and its six active alkaloids on six cytochrome P450 isoforms in human liver microsomes

Abstract

Huanglian (Rhizoma Coptidis) as a popular herb has been used for the treatment of various diseases such as diarrhea, eye inflammation and women's abdominal ailments. Alkaloids are considered to be responsible for its pharmacological effects. In this investigation, Huanglian and its six alkaloids (coptisine, epiberberine, berberine, jateorrhizine, palmatine and magnoflorine) were systematically evaluated for their inhibition of six cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes by the LC-MS/MS method. Huanglian showed the strongest inhibition of CYP2D6, followed by CYP1A2 and CYP3A4-T. The IC 50 values were 5.8 μg/mL, 36.8 μg/mL and 59.2 μg/mL, respectively. Of the constituents tested, coptisine and epiberberine showed strong inhibition of CYP2D6 with IC 50 values of 4.4μM and 7.7μM; berberine, jateorrhizine and palmatine showed weak inhibition of CYP2D6 with IC 50 values of 45.5μM, 49.4μM and 92.6μM, respectively; jateorrhizine showed moderate inhibition of CYP3A4-T with an IC 50 value of 13.3μM; coptisine showed weak inhibition of CYP1A2 with an IC 50 value of 37.3μM. In addition, activation was observed in coptisine/CYP2C9 and palmatine/CYP2C9/ CYP2C19. Other CYP450 isoforms were not affected markedly by the six alkaloids. In conclusion, Huanglian showed in vitro inhibition of CYP2D6, the inhibition might be contributed mostly by protoberberine alkaloids, especially coptisine and epiberberine. Herb-drug interactions may occur through the CYP2D6 inhibition. Copyright © 2011 John Wiley & Sons, Ltd.