College of Pharmacy, Beihua University, 3999 Binjiang East Road, Jilin, Jilin, 132013, China.
College of Pharmacy, Beihua University, 3999 Binjiang East Road, Jilin, Jilin, 132013, China.
Eur J Pharmacol. 2021 Nov 5;910:174442. doi: 10.1016/j.ejphar.2021.174442. Epub 2021 Sep 4.
The aim of this study was to analyze the active components of Schisandra chinensis on liver injury and its mechanism in mice by network pharmacology. The active components of S. chinensis were found through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and their corresponding targets were predicted. The targets of liver injury were searched through Therapeutic Targets Database (TTD), DisGeNET and drugbank databases, and the Venn diagram was constructed to obtain the action targets. The "drug-active component-target" network and protein-protein interaction network (PPI) were constructed by using STRING database and Cytoscape software, and the key targets were further screened by the enrichment analysis of relevant KEGG pathways. Finally, a CCl-induced mouse liver injury model was established to verify the efficacy and related targets of S. chinensis and clarify its mechanism. Eight active components and 56 related targets of S. chinensis were screened out based on their oral bioavailability (OB) and drug likeness (DL). Five targets of S. chinensis related to liver injury were found by using the Venn diagram. The key targets, namely Ptgs2 and Nos2 genes, were further screened out by constructing a PPI network, and Schisandrol B (SCB) was considered the key component most closely related to the liver injury in S. chinensis. The results indicate that SCB may play a role in the treatment of the CCl-induced liver injury by down-regulating the expression of iNOS and COX-2, and regulating the expression of NF-κB and IL-17 signaling pathway to inhibit the expression of proinflammatory factors.
本研究旨在通过网络药理学分析五味子对小鼠肝损伤的活性成分及其作用机制。通过中药系统药理学数据库和分析平台（TCMSP）找到了五味子的活性成分，并预测了它们的相应靶点。通过治疗靶点数据库（TTD）、DisGeNET 和 drugbank 数据库搜索肝损伤的靶点，并构建 Venn 图以获得作用靶点。通过 STRING 数据库和 Cytoscape 软件构建“药物-活性成分-靶点”网络和蛋白质-蛋白质相互作用网络（PPI），并通过相关 KEGG 通路的富集分析进一步筛选关键靶点。最后，建立 CCl 诱导的小鼠肝损伤模型，验证五味子的疗效及其相关靶点，阐明其作用机制。基于口服生物利用度（OB）和药物相似性（DL），筛选出五味子的 8 种活性成分和 56 个相关靶点。通过 Venn 图发现五味子与肝损伤相关的 5 个靶点。通过构建 PPI 网络进一步筛选出关键靶点，即 Ptgs2 和 Nos2 基因，认为五味子中与肝损伤关系最密切的关键成分是五味子醇 B（SCB）。结果表明，SCB 可能通过下调 iNOS 和 COX-2 的表达，调节 NF-κB 和 IL-17 信号通路的表达，抑制促炎因子的表达，从而发挥治疗 CCl 诱导的肝损伤的作用。
