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ABSTRACT: Background
Daidzein is a soybean isoflavone that has been shown in previous studies to have anti-inflammatory and antioxidant effects. However, it remains unknown whether daidzein plays a protective role against concanavalin A (Con A)-induced autoimmune hepatitis (AIH).Methods
In this study, an animal model of AIH was constructed by intravenous injection of Con A (15 mg/kg). Daidzein (200 mg/kg/d) was intraperitoneally administered to mice for 3 days before the Con A injection. Alpha mouse liver 12 (AML-12) cells were incubated in the absence or presence of daidzein to determine whether daidzein can alleviate Con A-induced hepatotoxicity.Results
The findings showed that pretreatment with daidzein significantly reduced Con A-induced oxidative stress and hepatocyte apoptosis in Con A-induced liver injury. Pretreatment with daidzein significantly prevented the decrease of intrahepatic protein levels of phosphorylated Akt (p-Akt), phosphorylated GSK3β (p-GSK3β), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NOQ1 (NAD(P)H quinone dehydrogenase 1) in response to Con A administration. Meanwhile, malondialdehyde (MDA) production was reduced, and glutathione peroxidase (GPX), superoxide dismutase (SOD) activity, and SOD2 mRNA expression were elevated in daidzein-pretreated livers. In in vitro experiments, daidzein pretreatment prevented Con A-induced murine hepatocyte death. This effect was partly diminished by an inhibitor of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway.Conclusions
These results indicate that daidzein pretreatment attenuates Con A-induced liver injury through the Akt/GSK3β/Nrf2 pathway. Our findings provide new insights into the use of plant-derived products for AIH treatment beyond immunosuppression.
SUBMITTER: Li SL
PROVIDER: S-EPMC8421986 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
Li Shang-Lin SL Cao Rui R Hu Xiao-Fan XF Xiong Peng P Zhao Guang-Yuan GY Xie Ya-Nan YN Wang Zhi-Min ZM Li Ya-Kun YK Yang Bo B Yang Jun J
Annals of translational medicine 20210801 15
<h4>Background</h4>Daidzein is a soybean isoflavone that has been shown in previous studies to have anti-inflammatory and antioxidant effects. However, it remains unknown whether daidzein plays a protective role against concanavalin A (Con A)-induced autoimmune hepatitis (AIH).<h4>Methods</h4>In this study, an animal model of AIH was constructed by intravenous injection of Con A (15 mg/kg). Daidzein (200 mg/kg/d) was intraperitoneally administered to mice for 3 days before the Con A injection. A ...[more]