A hepatoprotection study of Radix Bupleuri on acetaminophen-induced liver injury based on CYP450 inhibition.
10.1016/S1875-5364(19)30073-1
- Author:
Yu-Xin WANG
1
,
2
;
Yi DU
3
;
Xia-Fei LIU
3
;
Fang-Xiu YANG
3
;
Xiao WU
3
;
Li TAN
4
;
Yi-Hong LU
2
,
5
;
Jing-Wei ZHANG
6
;
Fang ZHOU
6
;
Guang-Ji WANG
7
Author Information
1. Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
2. Jiangsu Institute for Food and Drug Control, Nanjing 210019, China.
3. Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
4. Jiangsu Institute for Food and Drug Control, Nanjing 210019, China.
5. Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
6. Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
7. Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: guangjiwang@hotmail.com.
- Publication Type:Journal Article
- Keywords:
Acetaminophen;
Acute liver injury;
Cytochrome P450 enzymes;
Hepatoprotection;
Radix Bupleuri
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(7):517-524
- CountryChina
- Language:English
-
Abstract:
We investigated the potential hepatoprotective effect of Radix Bupleuri (RB) by inducing acute liver injury (ALI) in an animal model using acetaminophen (APAP) after pretreatment with RB aqueous extract for three consecutive days. Compared to those of the APAP group, the biochemical and histological results of the RB pretreatment group showed lower serumaspartate transaminase (AST) and alanine transaminase (ALT) levels as well as less liver damage. Pharmacokinetic study of the toxicity related marker acetaminophen-cysteine (APC) revealed a lower exposure level in rats, suggesting that RB alleviated APAP-induced liver damage by preventing glutathione (GSH) depletion. The results of cocktail approach showed significant inhibition of CYP2E1 and CYP3A activity. Further investigation revealed the increasing of CYP2E1 and CYP3A protein was significantly inhibited in pretreatment group, while no obvious effect on gene expression was found. Therefore, this study clearly demonstrates that RB exhibited significant protective action against APAP-induced acute live injury via pretreatment, and which is partly through inhibiting the increase of activity and translation of cytochrome P450 enzymes, rather than gene transcription.
