Effects of Schisandrae Chinensis Fructus induced CYPs and Nrf2 activation on acute liver injury induced by acetaminophen.
10.19540/j.cnki.cjcmm.20180625.006
- Author:
Bing-Xun QIU
1
;
Ke LIU
1
;
Li ZOU
1
;
Hui-Feng ZHU
1
;
Shan FENG
1
Author Information
1. College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China.
- Publication Type:Journal Article
- Keywords:
CYP450s;
N-acetyl-p-benzoquinoneimine;
Schisandrae Chinensis Fructus;
acetaminophen;
hepatotoxicity
- MeSH:
Acetaminophen;
Animals;
Chemical and Drug Induced Liver Injury;
Cytochrome P-450 Enzyme System;
Drugs, Chinese Herbal;
Liver;
NF-E2-Related Factor 2;
Rats;
Rats, Sprague-Dawley
- From:
China Journal of Chinese Materia Medica
2018;43(24):4908-4915
- CountryChina
- Language:Chinese
-
Abstract:
Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level (<0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity.
