Li Yan, Lu Ying-Yuan, Meng Yu-Qing, Du Zhi-Yong, Gao Peng, Zhao Ming-Bo, Jiang Yong, Tu Peng-Fei, Guo Xiao-Yu
School of Pharmaceutical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Biomed Chromatogr. 2021 Oct;35(10):e5171. doi: 10.1002/bmc.5171. Epub 2021 May 31.
Notoginseng total saponins (NS), safflower total flavonoids (SF), and the combination of NS and SF, namely CNS, are used for the treatment of cardiovascular diseases in clinic. This study developed a cocktail assay involving seven cytochrome P450 (CYP) enzymes to elucidate the effect of NS, SF, and CNS on CYP enzymes and to explore the synergistic effect of CNS in terms of CYP enzymes. Ultra-performance liquid chromatography-MS and reverse-transcription polymerase chain reaction were applied to detect the activities and mRNA expression levels of CYP enzymes. SF exhibited inhibitory effects on CYP1A2, 2B1, 2E1, and 2C11 and induction effects on CYP2C19 and 2D4. NS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C11, 2C19, and 2D4. CNS exhibited induction effects on CYP1A2, 2B1, 2E1, 2C19, and 2D4 and inhibitory effects on CYP3A1 in vivo. Moreover, mRNA expression results were consistent with pharmacokinetic results. Potential herb-drug interactions should be studied closely when SF, NS, or CNS with clinical drugs are metabolized by CYP1A2, 2B1, 2E1, 2C11, 2C19, 2D4, and 3A1. CNS could change the inhibition or induction effects of CYP compared to the NS group, which might be one of the causes for the synergistic effects of the combination of NS and SF.
三七总皂苷（NS）、红花总黄酮（SF）以及NS与SF的组合即CNS，在临床上用于治疗心血管疾病。本研究开发了一种包含七种细胞色素P450（CYP）酶的鸡尾酒式检测方法，以阐明NS、SF和CNS对CYP酶的影响，并从CYP酶方面探索CNS的协同作用。应用超高效液相色谱-质谱联用仪和逆转录聚合酶链反应来检测CYP酶的活性和mRNA表达水平。SF对CYP1A2、2B1、2E1和2C11表现出抑制作用，对CYP2C19和2D4表现出诱导作用。NS对CYP1A2、2B1、2E1、2C11、2C19和2D4表现出诱导作用。CNS在体内对CYP1A2、2B1、2E1、2C19和2D4表现出诱导作用，对CYP3A1表现出抑制作用。此外，mRNA表达结果与药代动力学结果一致。当SF、NS或CNS与临床药物经CYP1A2、2B1、2E1、2C11、2C19、2D4和3A1代谢时，应密切研究潜在的草药-药物相互作用。与NS组相比，CNS可能会改变CYP的抑制或诱导作用，这可能是NS与SF组合产生协同作用的原因之一。
