1. Schisantherin D from Schisandra chinensis (Turcz.) Baill. exhibits anti-liver fibrosis capacity via modulating ETBR involved signaling, an in vitro and in vivo study
- Author
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Chi Li, Yang-Jie Ru, Quan-Yue Lin, Guang-Chun Gao, Yu-Die Yang, Xiao-Qin Zhang, Jin-Lai Gao, Shi-Hui Liu, Chu-Wei Zheng, Lin Wang, Ya-Xin Zheng, and Ji-Ming Wu
- Subjects
Pharmacology ,Liver Cirrhosis ,Aflatoxin B1 ,Molecular Structure ,NF-E2-Related Factor 2 ,Tumor Necrosis Factor-alpha ,General Medicine ,Dioxoles ,Receptor, Endothelin B ,Lignans ,Transforming Growth Factor beta1 ,Mice ,Transforming Growth Factor beta ,Drug Discovery ,Animals ,Humans ,Acetaminophen ,Schisandra - Abstract
Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-β1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-β/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.
- Published
- 2022