Honokiol attenuates acetaminophen-induced acute liver injury by inhibiting hepatic CYP1A2 activity and improving liver mitochondrial dysfunction.
10.1016/j.chmed.2023.01.002
- Author:
Xiaolei MIAO
1
;
Chengting JIN
1
;
Jiao LIU
1
;
Junjun WANG
1
;
Yong CHEN
1
Author Information
1. Hubei Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei University, Wuhan 430062, China.
- Publication Type:Journal Article
- Keywords:
CYP1A2;
Magnolia officinalis Rehd. et Wils.;
acetaminophen;
honokiol;
liver mitochondrial dysfunction;
oxidant stress
- From:
Chinese Herbal Medicines
2023;15(2):231-239
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Acetaminophen (APAP) overdose is a common cause of liver injury. This study aimed to investigate the protective effect of honokiol (Hon) against APAP-induced hepatotoxicity and its potential mechanism.
METHODS:C57BL/6 mice were administrated with Hon (10 and 30 mg/kg) after APAP (300 mg/kg) treatment. On 1.5 h and 5 h after Hon treatment, mice were sacrificed. Serum and liver were collected. And then, liver injury-related indexes, APAP metabolism-related indexes, mitochondrial respiratory chain function-related indexes, and mitochondrial membrane function-related protein expression were evaluated.
RESULTS:It was found that Hon significantly decreased serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity and glutathione (GSH) depletion, increased hepatic catalase (CAT) and GSH peroxidase (GSH-Px) activities, reduced hepatic MDA and 3-nitrotyrosine contents, inhibited hepatic CYP1A2 activity and APAP protein adducts (APAP-CYS) formation. Meanwhile, oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased, whereas the release of H2O2 in the mitochondria was decreased following Hon treatment. Furthermore, Hon markedly down-regulated p-JNK in both cytosol and mitochondria, and obviously inhibited the release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from mitochondria to cytosol.
CONCLUSION:Hon alleviated APAP-induced liver injury through the following pathways: Reducing the production of APAP-CYS by inhibiting CYP1A2 activity; Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT, GSH-Px and GSH; Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV; Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria, thereby reducing the release of AIF and EndoG.
