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Daidzein ameliorated concanavalin A-induced liver injury through the Akt/GSK-3β/Nrf2 pathway in mice.


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

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Daidzein ameliorated concanavalin A-induced liver injury through the Akt/GSK-3β/Nrf2 pathway in mice.

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]

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