Shi Xue, Sun Ruimin, Zhao Yan, Fu Rong, Wang Ruiwen, Zhao Huanyu, Wang Zhecheng, Tang Fan, Zhang Ning, Tian Xiaofeng, Yao Jihong
Department of Pharmacology, Dalian Medical University Dalian 116044 China
Department of Pharmacy, First Affiliated Hospital of Xinxiang Medical University Xinxiang 453100 China.
RSC Adv. 2018 Jun 5;8(36):20411-20422. doi: 10.1039/c8ra00798e. eCollection 2018 May 30.
Salvianolic acid A (SalA) is a water-soluble phenolic carboxylic acid extracted from that has extensive pharmacological activities and plays an essential role in liver disease treatment. However, the mechanism of SalA in treating alcoholic liver disease (ALD) remains unclear. Here, we studied the protective effects of SalA on chronic ethanol-induced liver injury involving Sirtuin 1 (SIRT1)-mediated autophagy activation. The results showed that SalA pretreatment reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG) and cholesterol (TC) and enhanced hepatic cell viability while mitigating apoptosis and hepatic steatosis . Furthermore, SalA protected against chronic ethanol-induced liver injury by restoring autophagosome-lysosome fusion, as indicated by the increased expression levels of LC3-II, cathepsin B, lysosomal-associated membrane protein 2 (LAMP-2), and RAB7 and the decreased expression of SQSTM1. More importantly, pretreatment with SalA significantly up-regulated the expression of SIRT1, an NAD-dependent deacetylase. These increased levels of SIRT1 stimulated autophagy under conditions of chronic ethanol exposure. Interestingly, SIRT1 siRNA abrogated SalA-induced autophagosome-lysosome fusion. This finding indicates that the protective effects of SalA are associated with SIRT1 activation. Collectively, our study demonstrates that SalA pretreatment protects against chronic ethanol-induced liver injury the SIRT1-mediated restoration of autophagosome-lysosome fusion.
丹参酸A（SalA）是一种从[具体来源未给出]中提取的水溶性酚类羧酸，具有广泛的药理活性，在肝病治疗中发挥着重要作用。然而，SalA治疗酒精性肝病（ALD）的机制仍不清楚。在此，我们研究了SalA对慢性乙醇诱导的肝损伤的保护作用，涉及沉默调节蛋白1（SIRT1）介导的自噬激活。结果表明，SalA预处理降低了丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、甘油三酯（TG）和胆固醇（TC）的水平，增强了肝细胞活力，同时减轻了细胞凋亡和肝脂肪变性。此外，SalA通过恢复自噬体-溶酶体融合来保护肝脏免受慢性乙醇诱导的损伤，这表现为LC3-II、组织蛋白酶B、溶酶体相关膜蛋白2（LAMP-2）和RAB7表达水平升高以及SQSTM1表达降低。更重要的是，SalA预处理显著上调了NAD依赖性脱乙酰酶SIRT1的表达。在慢性乙醇暴露条件下，这些升高的SIRT1水平刺激了自噬。有趣的是，SIRT1 siRNA消除了SalA诱导的自噬体-溶酶体融合。这一发现表明SalA的保护作用与SIRT1激活有关。总体而言，我们的研究表明，SalA预处理通过SIRT1介导的自噬体-溶酶体融合恢复来保护肝脏免受慢性乙醇诱导的损伤。
