Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied.

华法林是一种常用的抗凝药，是香豆素的衍生物。细胞色素P450 2C9（CYP2C9）在香豆素转化中起关键作用，因此影响华法林剂量的确定。许多因素包括饮食化合物，例如芝麻素，咖啡酸和阿魏酸都可以调节CYP2C9的活性。本研究检验了芝麻素，淫羊min素，咖啡酸和阿魏酸通过抑制肝脏CYP2C9降低华法林7-羟基化速率的假设。实验是在人类供体的肝微粒体上进行的。结果表明，在浓度为5至500 nM的芝麻素存在下，华法林7-羟基化的速率显着降低，而不受芝麻素的影响，咖啡酸和阿魏酸的浓度范围相同。动力学分析表明，芝麻素的抑制作用非竞争性，Ki = 202±18 nM。总之，我们的结果体外研究表明，芝麻素能够抑制华法林的主要代谢物7-羟基华法林的形成。在华法林治疗的患者中，食用大量含芝麻素的食物或膳食补充剂可能产生的负面影响有待进一步研究。