Mechanistic understanding of the inhibitory effect of cytochrome P450 3A4 and 3A5 by Wuzhi tablet (Schisandra sphenanthera extract)
10.16438/j.0513-4870.2022-0651
- VernacularTitle:五酯片提取物对人CYP3A4及CYP3A5重组酶活性的抑制作用及其机制
- Author:
Xiao-ling QIN
1
;
Wen-hai DUAN
1
;
Jia-li LI
2
;
Min HUANG
2
;
Hui-chang BI
3
Author Information
1. Guangdong Food and Drug Vocational College, Guangzhou 510520, China
2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
3. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
- Publication Type:Research Article
- Keywords:
Wuzhi tablet;
italic>Schisandra sphenanthera;
CYP3A4;
CYP3A5;
herb-drug interaction
- From:
Acta Pharmaceutica Sinica
2022;57(8):2453-2460
- CountryChina
- Language:Chinese
-
Abstract:
Wuzhi tablet (WZ) is a prescribed herbal medicine extracted from Schisandra sphenanthera, which is widely used to protect the liver injury and drug-induced hepatotoxicity in clinical practices. Previous studies showed that WZ significantly increased the blood concentrations of tacrolimus, cyclosporine A, paclitaxel by inhibiting the cytochrome P450 3A (CYP3A)-mediated metabolism. CYP3A4 and CYP3A5 are the most important isoenzymes among the CYP3A subfamily. However, there are some differences in the catalytic and inhibitory activities between CYP3A4 and CYP3A5, which may lead to different risk of drug-drug and herb-drug interactions, and the risks may be further amplified in vivo. Currently, few reports have compared the herbal medicine inhibitory effects between CYP3A4 and CYP3A5 mediated metabolic reactions. Therefore, detailing the inhibitory effect of WZ on CYP3A4 and CYP3A5 will help understand and predict the potential herb-drug interaction. The results showed that WZ inhibited CYP3A4 and CYP3A5 in a NADPH-, time- and concentration- dependent manner. WZ showed more potent inhibition on CYP3A5 than CYP3A4. Cautions warranted when combining WZ with other therapeutic drugs to avoid the potential herb-drug interaction.
