Wang Qun, Tang Tiantian, Wu Zengguang, Yang Hong, Gao Yuan, Zhang Shiyu, Song Xinli, Chen Xiaolan
Guizhou University of Traditional Chinese Medicine, Huaxi University Town, Guiyang, China.
National Research Center of Miao Medicine and Engineering Technology, Huaxi University Town, Guiyang, China.
Front Pharmacol. 2023 Apr 14;14:1175896. doi: 10.3389/fphar.2023.1175896. eCollection 2023.
To investigate the dominant metabolic enzymes of six effective components (astragaloside IV, glycyrrhizic acid, calycosin-glucuronide, formononetin, ononin, calycosin-7-O-β-D- glucoside) of Huangqi Liuyi decoction extract (HQD). Mouse liver microsomes were prepared. The effects of specific inhibitors of CYP450 enzymes on the metabolism of six effective components of HQD were studied using liver microsomal incubation . The chemical inhibitors of CYP2C37 inhibit the metabolism of glycyrrhizic acid and astragaloside IV. Formononetin and astragaloside IV metabolism is inhibited by the chemical inhibitors of CYP2C11. The chemical inhibitors of CYP2E1 and CYP1A2 inhibit the metabolism of calycosin-glucuronide. Chemical CYP3A11 inhibitors prevent formononetin and glycyrrhizic acid from being metabolized. However, no inhibitor significantly affected the metabolism of ononin and calycosin-7-O-β-D-glucoside. CYP2C37 may be involved in the metabolism of astragaloside IV and glycyrrhizic acid, the metabolism of astragaloside IV and formononetin may be related to CYP2C11, the metabolism of calycosin-glucuronide may be related to CYP1A2 and CYP2E1, and CYP3A11 may be involved in the metabolism of glycyrrhizic acid and formononetin. This research provides an experimental basis for exploring the pharmacokinetic differences caused by metabolic enzymes.
研究黄芪六一汤提取物（HQD）中六种有效成分（黄芪甲苷、甘草酸、毛蕊异黄酮葡萄糖醛酸苷、芒柄花素、鹰嘴豆芽素A、毛蕊异黄酮-7-O-β-D-葡萄糖苷）的主要代谢酶。制备小鼠肝微粒体。采用肝微粒体孵育法研究细胞色素P450酶（CYP450）特异性抑制剂对HQD六种有效成分代谢的影响。CYP2C37的化学抑制剂抑制甘草酸和黄芪甲苷的代谢。CYP2C11的化学抑制剂抑制芒柄花素和黄芪甲苷的代谢。CYP2E1和CYP1A2的化学抑制剂抑制毛蕊异黄酮葡萄糖醛酸苷的代谢。CYP3A11化学抑制剂可阻止芒柄花素和甘草酸的代谢。然而，没有抑制剂对鹰嘴豆芽素A和毛蕊异黄酮-7-O-β-D-葡萄糖苷的代谢产生显著影响。CYP2C37可能参与黄芪甲苷和甘草酸的代谢，黄芪甲苷和芒柄花素的代谢可能与CYP2C11有关，毛蕊异黄酮葡萄糖醛酸苷的代谢可能与CYP1A2和CYP2E1有关，CYP3A11可能参与甘草酸和芒柄花素的代谢。本研究为探讨代谢酶引起的药代动力学差异提供了实验依据。
