The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, Zhejiang 323000, People's Republic of China.
Department of Pharmacy, The First People's Hospital of Yuhang District, Hangzhou, Zhejiang 311100, People's Republic of China.
Drug Des Devel Ther. 2020 May 19;14:1909-1919. doi: 10.2147/DDDT.S249308. eCollection 2020.
The aim of the present study was to investigate the interactions of the main components of root (ie, p-coumaric acid, acacetin, apigenin, buddleoside and Diosmetin-7-O-β-D-glucopyranoside) with cytochrome P450 3A enzyme activity both in vitro and in vivo.
In vitro inhibition of drugs was assessed by incubating rat liver microsomes (RLMs) with a typical P450 3A enzyme substrate, midazolam, to determine their 50% inhibitory concentration (IC50) values. For the in vivo study, healthy male Sprague Dawley rats were consecutively administered acacetin or apigenin for 7 days at the dosage of 5 mg/kg after being randomly divided into 3 groups: Group A (control group), Group B (acacetin group) and Group C (apigenin group).
Among the five main components of root, only acacetin and apigenin showed inhibitory effects on the cytochrome P450 3A enzyme in vitro. The IC50 values of acacetin and apigenin were 58.46 μM and 8.20 μM, respectively. Additionally, the in vivo analysis results revealed that acacetin and apigenin could systemically inhibit midazolam metabolism in rats. The T, AUC and C of midazolam in group B and group C were significantly increased (<0.05), accompanied by a significant decrease in V and CL (<0.05).
Acacetin and apigenin could inhibit the activity of the cytochrome P450 3A enzyme in vitro and in vivo, indicating that herbal drug interactions might occur when taking root and midazolam synchronously.
本研究旨在探讨 根的主要成分（即对香豆酸、芹菜素、木樨草素、梓醇和香叶木素-7-O-β-D-吡喃葡萄糖苷）与细胞色素 P450 3A 酶在体外和体内的相互作用。
通过在孵育大鼠肝微粒体（RLMs）与典型的 P450 3A 酶底物咪达唑仑时评估药物的体外抑制作用，以确定其 50%抑制浓度（IC50）值。对于体内研究，将健康雄性 Sprague Dawley 大鼠随机分为 3 组，每组 8 只：A 组（对照组）、B 组（芹菜素组）和 C 组（木樨草素组），连续 7 天每天以 5mg/kg 的剂量给予芹菜素或木樨草素。
在 根的五种主要成分中，只有芹菜素和木樨草素对细胞色素 P450 3A 酶表现出体外抑制作用。芹菜素和木樨草素的 IC50 值分别为 58.46 μM 和 8.20 μM。此外，体内分析结果表明，芹菜素和木樨草素可以系统地抑制咪达唑仑在大鼠体内的代谢。B 组和 C 组的咪达唑仑 T、AUC 和 C 显著增加（<0.05），V 和 CL 显著降低（<0.05）。
芹菜素和木樨草素可以体外和体内抑制细胞色素 P450 3A 酶的活性，表明同时服用 根和咪达唑仑可能会发生草药药物相互作用。
