Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China.
Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China; Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Phytomedicine. 2024 Feb;124:155330. doi: 10.1016/j.phymed.2023.155330. Epub 2023 Dec 30.
Hepatic fibrosis is the pivotal determinant in the progression of chronic liver diseases towards cirrhosis or advanced stages. Studies have shown that Schisantherin A (Sin A), the primary active compound from Schizandra chinensis (Turcz.) Baill., exhibits anti-hepatic fibrosis effects. However, the mechanism of Sin A in liver fibrosis remain unclear.
To examine the effects and underlying mechanism of Sin A on hepatic fibrosis.
The effects and mechanism of Sin A were investigated using liver fibrosis mouse models induced by carbon tetrachloride (CCl) or dimethylnitrosamine (DMN), as well as HO-induced hepatocyte injury in vitro.
Sin A treatment ameliorated hepatocyte injury, inflammation, hepatic sinusoidal capillarization, and hepatic fibrosis in both CCl-induced and DMN-induced mice. Sin A effectively reversed the reduction of DDAH1 expression, the p-eNOS/eNOS ratio and NO generation and attenuated the elevation of hepatic ADMA level induced by CCl and DMN. Knockdown of DDAH1 in hepatocytes not only triggered hepatocyte damage, but it also counteracted the effect of Sin A on protecting hepatocytes in vitro.
Our findings indicate that Sin A ameliorates liver fibrosis by upregulating DDAH1 to protect against hepatocyte injury. These results provide compelling evidence for Sin A treatment in liver fibrosis.
肝纤维化是慢性肝病向肝硬化或晚期进展的关键决定因素。研究表明，五味子甲素（Sin A）是五味子（Turcz.）Baill. 的主要活性化合物，具有抗肝纤维化作用。然而，Sin A 治疗肝纤维化的机制尚不清楚。
研究 Sin A 对肝纤维化的作用及机制。
采用四氯化碳（CCl）或二甲基亚硝胺（DMN）诱导的肝纤维化小鼠模型以及体外 HO 诱导的肝细胞损伤，研究 Sin A 的作用和机制。
Sin A 治疗可改善 CCl 和 DMN 诱导的小鼠肝细胞损伤、炎症、肝窦毛细血管化和肝纤维化。Sin A 可有效逆转 CCl 和 DMN 诱导的 DDAH1 表达减少、p-eNOS/eNOS 比值和 NO 生成减少以及肝 ADMA 水平升高。肝细胞中 DDAH1 的敲低不仅引发了肝细胞损伤，还抵消了 Sin A 体外保护肝细胞的作用。
我们的研究结果表明，Sin A 通过上调 DDAH1 来改善肝纤维化，从而保护肝细胞免受损伤。这些结果为 Sin A 治疗肝纤维化提供了有力的证据。
