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.

过量的化学肝毒物（酒精、黄曲霉毒素 B1）、氧化药物（对乙酰氨基酚）和一些细胞因子（ET-1、TGF-β1）可诱发慢性或急性肝损伤。之后，如果不采取措施，就会出现严重的肝病，特别是肝纤维化（LF），给人类健康带来威胁。发现S. chinensis的二苯并环辛二烯木脂素(SCDLs)通过阻断内皮素 B 受体 (ETBR)作为保肝成分。而对其抗LF机制的研究，尤其是其精制五味子素D（SC-D）的作用仍缺乏研究。因此本研究旨在通过体外和体内研究 SC-D 的抗纤维化作用。化验。生物信息学分析揭示了ETBR与LF相关信号通路（如TGF-β/Smad和Nrf2/ARE）中的Smad2、Smad3、Nrf2等密切相关。肝脏的组织病理学染色显示 SC-D 处理的 LF 小鼠的恢复趋势。SC-D 还调节LF 小鼠肝脏中 ETBR 和纤维化或抗氧化相关蛋白（如 TIMP1、p-Smad2/3、Nrf2、Smad7等）的表达。与 LF 小鼠相比，SC-D 治疗小鼠的血清 TNF-α、COL I、ALT、AST 和 LDH 水平也下调，而 GSH 表达上调。体外研究发现，SC-D 还通过转染 si-Smad7 或 si-Nrf2 将 LF 相关蛋白的表达调节到 LX-2 细胞的正常趋势，同时减弱其抗 LX-2 增殖作用。因此，SC-D 的抗 LF 方法显示出与调节 ETBR 相关的纤维化和抗氧化相关信号传导的关系。此外，Smad7 和 Nrf2 可能是 SC-D 介导的抗 LF 作用的关键因素。