Sauchinone, an active lignan isolated from the aerial parts of Saururus chinensis\n(Saururaceae), exhibits anti-inflammatory, anti-obesity, anti-hyperglycemic, and anti-hepatic steatosis\neffects. As herbââ?¬â??drug interaction (HDI) through cytochrome P450s (CYPs)-mediated metabolism\nlimits clinical application of herbs and drugs in combination, this study sought to explore the enzyme\nkinetics of sauchinone towards CYP inhibition in in vitro human liver microsomes (HLMs) and\nin vivo mice studies and computational molecular docking analysis. In in vitro HLMs, sauchinone\nreversibly inhibited CYP2B6, 2C19, 2E1, and 3A4 activities in non-competitive modes, showing\ninhibition constant (Ki) values of 14.3, 16.8, 41.7, and 6.84 Ã?¼M, respectively. Also, sauchinone\ntime-dependently inhibited CYP2B6, 2E1 and 3A4 activities in vitro HLMs. Molecular docking study\nshowed that sauchinone could be bound to a few key amino acid residues in the active site of CYP2B6,\n2C19, 2E1, and 3A4. When sibutramine, clopidogrel, or chlorzoxazone was co-administered with\nsauchinone to mice, the systemic exposure of each drug was increased compared to that without\nsauchinone, because sauchinone reduced the metabolic clearance of each drug. In conclusion, when\nsauchinone was co-treated with drugs metabolized via CYP2B6, 2C19, 2E1, or 3A4, sauchinoneââ?¬â??drug\ninteractions occurred because sauchinone inhibited the CYP-mediated metabolic activities.
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