Inhibition of Human Liver Cytochrome P450 2C8 and 3A4 by Sanguinarine

Abstract: Sanguinaria, a benzo[c]phenanthridine alkaloid extracted from the root of Sanguinaria canadenis and other poppy-fumaria species, exhibits many biological activities, such as antimicrobial, antiinflammatory, antioxidant, antitumor activities, and singlet oxygen generation potential [1]. As antibiotics or anticancer drug, sanguinaria is likely to be used in combination with various synthetic drug in most case, thus it is necessary to evaluate potential pharmacokinetics drug-drug interactions induced by sanguinaria. An in vitro study revealed that sanguinaria can caused competitive inhibition of human CYP1A2 with Ki of 2 mM [2], but the inhibitory effects on other CYP enzymes remain unreported. In this study, the inhibition of sanguinariato on CYP3A4 and CYP2C8 displayed reversible inhibition. The kinetic parameters of reversible inhibition (Ki) are 2.2 mM for CYP3A4 and 8.82 mM for CYP2C8. Due to the limited pharmacokinetics data of sanguinaria in human, it is nigh impossible to evaluate its potential effects to human from in vitro data, further work will be done in the future. Reference: [1] Curr drug metab, 2007; 8:173-176 [2] Toxicol lett, 2004; 151:375-387