Huang Ming-Yue, Wang Zhen-Zhen, Long Jiang-Lan, Yang Xin-Yu, Zhang Yi, Yan Dan
School of Pharmacy, Chengdu University of Traditional Chinese Medicine Chengdu 610075, China.
Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
Zhongguo Zhong Yao Za Zhi. 2021 Oct;46(20):5341-5350. doi: 10.19540/j.cnki.cjcmm.20210713.402.
The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic β cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic β cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic β cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic β cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, β-carotene and β-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic β cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic β cell dysfunction.
本研究基于网络药理学和分子对接技术，探讨金芪降糖片（JQJT）对胰腺β细胞功能障碍的治疗效果及潜在机制。利用中药系统药理学数据库与分析平台（TCMSP）检索JQJT三种中药材的化学成分和靶点。通过UniProt将基因转换为基因符号，并获取其与基因卡片（GeneCards）和比较毒理基因组学数据库（CTD）中胰腺β细胞功能相关靶点的交集。将药物、活性成分和共同靶点导入Cytoscape 3.8.2以绘制药物-成分-靶点网络。通过软件分析获得主要有效成分和靶点。将药物靶点和胰腺β细胞功能相关靶点分别导入STRING平台构建蛋白质-蛋白质相互作用（PPI）网络。通过Cytoscape 3.8.2合并两个PPI网络，并使用插件CytoNCA获得关键靶点。将从药物-成分-靶点网络和PPI网络获得的靶点导入DAVID进行基因本体（GO）分析和京都基因与基因组百科全书（KEGG）富集分析。使用AutoDock对主要活性成分和核心靶点进行分子对接，并使用Pymol绘制分子对接图。结果显示，与JQJT相关的活性成分有371个、靶点有203个，与胰腺β细胞损伤相关的靶点有2523个，涵盖136个共同靶点。结果揭示了核心靶点（如环氧化酶2（PTGS2）、环氧化酶1（PTGS1）、一氧化氮合酶2（NOS2）、雌激素受体1（ESR1）和视黄酸受体α（RXRA））和有效关键成分（如槲皮素、山奈酚、木犀草素、β-胡萝卜素和β-谷甾醇）。KEGG富集分析表明，主要涉及细胞凋亡、炎症等信号通路。分子对接结果表明，主要活性成分可与靶点自发结合。本研究初步揭示了JQJT通过多成分、多靶点、多途径改善胰腺β细胞损伤的机制，为JQJT治疗胰腺β细胞功能障碍提供了理论依据。
