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Schisandrin B ameliorates acute liver injury by regulating EGFR-mediated activation of autophagy

[Display omitted] •Schisandrin B is a bioactive lignan of Schisandrae Chinensis Fructus.•Schisandrin B ameliorates acute liver injury by acetaminophen (APAP).•Schisandrin B could inhibit inflammatory factors of HepG2 induced by APAP.•Schisandrin B regulate EGFR mediated activation of autophagy.•The...

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Published in:Bioorganic chemistry 2023-01, Vol.130, p.106272, Article 106272
Main Authors: Li, Xiankuan, Zhao, Ying, Gong, Sihan, Song, Tianbao, Ge, Jiaming, Li, Jiarong, Zhang, Jian, Fu, Kun, Zheng, Yanchao, Ma, Lin
Format: Article
Language:English
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Summary:[Display omitted] •Schisandrin B is a bioactive lignan of Schisandrae Chinensis Fructus.•Schisandrin B ameliorates acute liver injury by acetaminophen (APAP).•Schisandrin B could inhibit inflammatory factors of HepG2 induced by APAP.•Schisandrin B regulate EGFR mediated activation of autophagy.•The mechanism is that EGFR/TFEB signaling pathway is regulated. To investigate the role and possible molecular mechanism of Schisandrin B-induced cell autophagy in the prevention and treatment of APAP-induced liver injury. Molecular docking method was used to predict the interaction between Schisandrin B and the EGFR protein. HepG2 cells were treated with different concentrations of Schisandrin B for 24 h. Schisandrin B-induced autophagy of HepG2 cells was determined using real-time label-free cell analysis (RTCA), flow cytometry, immunofluorescence, PCR, and western blot. Flow cytometry and western blot were used to explore whether Schisandrin B-induced autophagy plays a role in the prevention and treatment of liver injury via the EGFR/TFEB signaling pathway. Schisandrin B treatment of APAP-induced HepG2 cells inhibited the production of TNF-α and IL-1β. Further, Schisandrin B downregulated EGFR protein expression and activated the EGFR/TFEB signaling pathway. Autophagy inhibition promoted APAP-induced apoptosis of HepG2 cells. Moreover, the protein expression levels of TFEB, LC3 and Beclin-1 were upregulated, whereas those of ATG3 and EGFR were downregulated. Schisandrin B can induce autophagy in HepG2 cells. Autophagy may play a role in the prevention and treatment of liver injury via the EGFR/TFEB signaling pathway. Activation of autophagy enhances the effect of Schisandrin B on APAP-induced liver injury.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2022.106272