PDF(Pubmed)
Abstract：
Liver fibrosis is currently a global health challenge with no approved therapy, with the activation of hepatic stellate cells being a principal factor. Lipophilic constituents in Salvia miltiorrhiza (LS) have been reported to improve liver function and reduce the indicators of liver fibrosis for patients with chronic hepatitis B induced hepatic fibrosis. However, the pharmacological mechanisms of LS on liver fibrosis have not been clarified. In this study, 71 active compounds, 342 potential target proteins and 22 signaling pathways of LS were identified through a network pharmacology strategy. Through text mining and data analysis, the JAK1/STAT3 signaling pathway was representatively selected for further experimental validation. We firstly confirmed the protective effect of LS on liver fibrosis in vivo by animal experiments. Hepatic stellate cells, which proliferated and displayed a fibroblast-like morphology similar to activated primary stellate cells, were applied to evaluate its underlying mechanisms. The results showed that LS could inhibit the cell viability, promote the cell apoptosis, decrease the expression of liver fibrosis markers, and downregulate the JAK1/STAT3 signaling pathway. These results demonstrated that LS could exert anti-liver-fibrosis effects by inhibiting the activation of HSCs and regulating the JAK1/STAT3 signaling pathway, which is expected to benefit its clinical application.
摘要：
肝纤维化目前是一个全球性的健康挑战，没有批准的治疗，肝星状细胞的激活是主要因素。据报道，丹参（LS）中的亲脂性成分可改善慢性乙型肝炎诱导的肝纤维化患者的肝功能并降低肝纤维化指标。然而,LS对肝纤维化的药理机制尚未阐明。在这项研究中,71个活性化合物，通过网络药理学策略鉴定了342个潜在的靶蛋白和22个LS信号通路。通过文本挖掘和数据分析,选择了代表性的JAK1/STAT3信号通路进行进一步的实验验证.我们首先通过动物实验证实了LS对体内肝纤维化的保护作用。肝星状细胞，其增殖并显示出类似于激活的原代星状细胞的成纤维细胞样形态，用于评估其潜在机制。结果表明，LS可以抑制细胞活力，促进细胞凋亡，降低肝纤维化标志物的表达，并下调JAK1/STAT3信号通路。这些结果表明，LS可以通过抑制HSCs的活化和调节JAK1/STAT3信号通路发挥抗肝纤维化作用，有望有利于其临床应用。
