Auriculasin has a wide range of pharmacological effects, including anticancer and anti-inflammatory effects. In this work, we explored the metabolic characteristics and inhibitory effect of auriculasin against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes in vitro. Auriculasin inhibited UGT1A6, UGT1A8, UGT1A10, UGT2B7, CYP2C9, and CYP3A4 strongly at a concentration of 100 μM. Different species showed significant differences in auriculasin metabolism, and metabolic characteristics were similar between pig and human. We identified seven metabolites, and hydroxylated auriculasin was the main metabolite. In addition, CYP2D6, CYP2C9, CYP2C19, and CYP2C8 were the major CYP isoforms involved in the metabolism of auriculasin. Molecular docking studies showed that noncovalent interactions between auriculasin and the CYPs are dominated by hydrogen bonding, π-π stacking, and hydrophobic interactions. Our in vitro study provides insights into the pharmacological and toxicological mechanisms of auriculasin.

中文翻译：

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大叶黄素的体外代谢及其对人细胞色素P450和UDP-葡萄糖醛酸转移酶的抑制作用。

大黄素具有广泛的药理作用，包括抗癌和抗炎作用。在这项工作中，我们探讨了耳菌素在体外对细胞色素P450（CYP）和UDP-葡萄糖醛酸转移酶（UGT）酶的代谢特征和抑制作用。大黄素以100μM的浓度强烈抑制UGT1A6，UGT1A8，UGT1A10，UGT2B7，CYP2C9和CYP3A4。不同物种在耳孢菌素的代谢上存在显着差异，并且猪和人之间的代谢特征相似。我们鉴定了7种代谢物，其中羟化耳菌素是主要的代谢物。此外，CYP2D6，CYP2C9，CYP2C19和CYP2C8是参与耳菌素代谢的主要CYP亚型。分子对接研究表明，auriculasin和CYP之间的非共价相互作用主要是氢键，π-π堆积和疏水相互作用。我们的体外研究提供了耳菌素的药理和毒理学机理的见解。