Inhibitory effect of Lygodium root on the cytochrome P450 3A enzyme and its pharmacokinetics in rats

Published: 5 August 2019| Version 1 | DOI: 10.17632/52gxvdnym2.1
yunfang Zhou


The aim of the present study was to investigate the interactions of the main components of Lygodium root (i.e., 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 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 seven days after being randomly divided into 3 groups: group A (control group), group B (5 mg/kg acacetin) and group C (5 mg/kg apigenin). Among the 5 main components of Lygodium 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 Tmax, AUC(0-t) and Cmax of midazolam in group B and group C were significantly increased (P<0.05), accompanied by a significant decrease in Vz/F and CLz/F (P<0.05). Apigenin and acacetin inhibited the activity of the cytochrome P450 3A enzyme both in vitro and in vivo, indicating that herbal drug interactions might occur when taking Lygodium root and midazolam synchronously.