Honokiol attenuates acetaminophen-induced acute liver injury by inhibiting hepatic CYP1A2 activity and improving liver mitochondrial dysfunction  

作　　者：Xiaolei Miao Chengting Jin Jiao Liu Junjun Wang Yong Chen 

机构地区：[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 [2]School of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China

出　　处：《Chinese Herbal Medicines》2023年第2期231-239,共9页中草药（英文版）

基　　金：supported by the Department of Education of Hubei Province,China(No.Q20181004).

摘　　要：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.

关 键 词：ACETAMINOPHEN CYP1A2 HONOKIOL liver mitochondrial dysfunction Magnolia officinalis Rehd.et Wils. oxidant stress 

分 类 号：R285.5[医药卫生—中药学]