Cryptotanshinone (CT) is the main active component in the root of Salvia miltiorrhiza Bunge (SMB) that displays antibacterial, anti-inflammatory and anticancer activities. In this study, we characterized phase I and phase II metabolism of CT in human liver microsomes in vitro and identified the metabolic enzymes (CYPs and UGTs) involved. The metabolites of CT generated by CYPs were detected using LC-MS/MS and the CYP subtypes involved in the metabolic reactions were identified using chemical inhibitors of CYP enzymes and recombinant human CYP enzymes (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Glucuronidation of CT was also examined, and the UGT subtypes involved in the metabolic reactions were identified using recombinant human UGT enzymes (1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15 and 2B17). After adding NADPH to the human liver microsomes incubation system, CT was transformed into 6 main dehydrogenation and hydroxylation metabolites. CYP2A6, CYP3A4 and CYP2C19 were the major contributors to the transformation of its hydroxylation metabolites. CYP2C19, CYP1A2 and CYP3A4 were the major contributors to the transformation of its hydrogenation metabolites in human liver microsomes. This study showed that the metabolites at m/z of 473 were mediated by UGT1A9 and that the metabolites at m/z of 489 were mediated by UGT2B7 and UGT2B4. CT was extensively metabolized by UGTs following metabolism by CYPs in the liver.

中文翻译：

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在体外通过人P450酶和尿苷二磷酸葡萄糖醛酸糖基转移酶表征隐丹参酮的代谢。

隐丹参酮（CT）是丹参（Salvia miltiorrhiza Bunge，SMB）根部的主要活性成分，具有抗菌，消炎和抗癌的作用。在这项研究中，我们表征了人肝微粒体中CT的I期和II期代谢，并确定了所涉及的代谢酶（CYP和UGT）。使用LC-MS / MS检测CYP产生的CT代谢物，并使用CYP酶和重组人CYP酶的化学抑制剂（CYP1A2，CYP2A6，CYP2C8，CYP2C9，CYP2C19，CYP2D6，和CYP3A4）。还检查了CT的葡萄糖醛酸苷化，并使用重组人UGT酶（1A1、1A3、1A4、1A5、1A6、1A7、1A8、1A9、1A10、2B4、2B7、2B15和2B17）鉴定了参与代谢反应的UGT亚型。 。将NADPH加入人肝微粒体温育系统后，CT被转化为6种主要的脱氢和羟基化代谢产物。CYP2A6，CYP3A4和CYP2C19是其羟基化代谢产物转化的主要贡献者。CYP2C19，CYP1A2和CYP3A4是其在人肝微粒体中氢化代谢物转化的主要贡献者。这项研究表明，m / z为473的代谢物是由UGT1A9介导的，m / z为489的代谢物是由UGT2B7和UGT2B4介导的。肝脏中CYP代谢后，CT被UGT广泛代谢。CYP3A4和CYP2C19是其羟基化代谢产物转化的主要贡献者。CYP2C19，CYP1A2和CYP3A4是其在人肝微粒体中氢化代谢物转化的主要贡献者。这项研究表明，m / z为473的代谢物是由UGT1A9介导的，m / z为489的代谢物是由UGT2B7和UGT2B4介导的。肝脏中CYP代谢后，CT被UGT广泛代谢。CYP3A4和CYP2C19是其羟基化代谢产物转化的主要贡献者。CYP2C19，CYP1A2和CYP3A4是其在人肝微粒体中氢化代谢物转化的主要贡献者。这项研究表明，m / z为473的代谢物是由UGT1A9介导的，m / z为489的代谢物是由UGT2B7和UGT2B4介导的。肝脏中CYP代谢后，CT被UGT广泛代谢。