Inhibitory effects of aconitine, mesaconitine and hypaconitine on cytochrome P4503A4
LI Han
WANG Yu-guang
MA Zeng-chun
TAN Hong-ling
XIAO Cheng-rong
TANG Xiang-lin
ZHANG Bo-li
GAO Yue
Abstract：Objective:To investigate inhibitory effects of aconitum alkaloids,the effective components of Radix Aconiti Lateralis Praeparata,on cytochrome P450 3A4 (CYP3A4).Methods:Dual luciferase reporter gene system was applied.Six kinds of aconitum alkaloids (aconitine,mesaconitine,hypaconitine,acetylaconitine,aconine and benzoylaconine) were screened for Pregnane X receptor activation by reporter gene assays,and ketoconazole was used as the positive control.Furthermore,LS174T cells were treated with various concentrations of aconitin,mesaconitine and hypaconitine.Then,their RNA and total protein were extracted to evaluate the regulating effect of alkaloids on CYP3A4 mRNA and protein expression by real time PCR and Western blot methods,respectively.Results:Reporter gene screening showed that aconitum alkaloids did not activate PXR,and had potential inhibitory effects on CYP3A4 enzyme.Meanwhile,dose-dependent inhibiton of the gene expression were observed in response to aconitine,mesaconitine and hypaconitine,and the levels of CYP3A4 protein expression were decreased by aconitine,mesaconitine and hypaconitine in varying degrees.Conclusion:Aconitine,mesaconitine and hypaconitine can down-regulate the gene and protein expression of CYP3A4 which could induce significant drug-drug interactions.
Keywords：aconitum alkaloidsCYP3A4real time PCRWestern blotdrug-drug interactions
Publication Date：2017-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 999-1004 )