Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease

Oroxylin a 促进 PGC-1α/Mfn2 信号传导,通过阻断酒精性肝病中的线粒体 ROS 来减轻肝细胞焦亡

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作者:Jun Kai, Xiang Yang, Zhimin Wang, Feixia Wang, Yan Jia, Shijun Wang, Shanzhong Tan, Anping Chen, Jiangjuan Shao, Feng Zhang, Zili Zhang, Shizhong Zheng

Background

It is well acknowledged that alcoholic liver disease (ALD) is widely prevalent all over the world, characterized by aberrant lipid deposition and excessive oxidative stress in hepatocytes. Recently, pyroptosis, a new type of programmed cell death, has been found in ALD, which provides new ideas for the treatment of ALD.

Conclusion

Our research revealed that oroxylin A could alleviate ALD via PGC-1α/Mfn2 signaling mediated canonical pyroptosis pathway resistance.

Methods

Male ICR mice were treated with the Lieber-De-Carli diet (Dyets) or isocaloric liquid diet for 8 weeks, and binge alcohol model was also used for ALD. Blood and livers were taken to evaluate the efficacy of oroxylin A. The levels of factors related to hepatocyte pyroptosis were measured via western blot analyses, immunofluorescence analyses and quantitative reverse transcriptase in vitro. Result: Our study found that oroxylin A suppressed hepatocyte pyroptosis through a NLRP3 inflammasome dependent-canonical caspase-1 pathway.

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