采用网络药理学与分子对接技术研究筋骨痛消丸治疗髌骨软化症的作用机制

摘要/Abstract

摘要： 目的：通过网络药理学和分子对接技术研究筋骨痛消丸治疗髌骨软化症（chondromalacia patellae）的作用机制。方法：首先通过中药系统药理学数据库与分析平台（TCMSP）挖掘筋骨痛消丸中各种中药的活性成分并预测其作用靶点，TCMSP数据库中缺失的中药利用文献检索与Swiss Target Prediction数据库获得有效成分及对应靶点。利用UniProt数据库，将获得的靶点蛋白的名称标准化。登录GeneCards、PharmGkb等数据库，获取髌骨软化症的疾病靶点。之后将药物靶点和疾病靶点取交集，制作出韦恩图。运用Cytoscape 软件，筛选并构建“药物-活性成分-交集靶点-疾病”网络；利用String数据库构建蛋白互作（PPI）网络，并使用R语言对预测靶点进行GO富集分析和KEGG通路分析。最后通过Autodock软件对药物的主要活性成分和核心作用靶点进行分子对接验证。结果：研究结果显示筛选得到筋骨痛消丸治疗髌骨软化症的活性成分188个及靶点249个，主要活性成分为槲皮素、柚皮素、山奈酚、木犀草素、β-谷甾醇等，PPI网络主要计算出AKT1、CASP8、CASP3、JUN、BCL2L1、MYC等6个关键靶点。GO富集分析涉及生物过程（BP）1458个，细胞组分（CC）19个，分子功能（MF）65个；KEGG通路富集分析筛选得到43条与髌骨软化相关的通路，主要作用于脂质和动脉粥样硬化信号通路、细胞凋亡信号通路、AGE-RAGE信号通路以及病毒相关信号通路等。分子对接结果表明，药物组成中的主要活性化合物能够分别与代表性的靶点结合并展现出较好的亲和力。结论：本研究表明筋骨痛消丸治疗髌骨软化症涉及多条信号通路及生物学过程，其主要活性成分山奈酚、木犀草素、槲皮素与关键靶点AKT1、CASP3、MYC的结合可能是发挥作用的重要机制之一。

关键词: font-size:medium, ">网络药理学；分子对接；筋骨痛消丸；髌骨软化症；作用机制

Abstract: Objective：To study the action mechanism of Jingutongxiao pill in the treatment of chondromalacia patellae based on network pharmacology and molecular docking. Methods： Firstly， the active ingredients of various Chinese herbs in Jingutongxiao pill were explored through the TCMSP database and their action targets were predicted. The active ingredients and action targets of the missing Chinese herb components in the TCMSP database were obtained by literature search and Swiss Target Prediction database， and the names of the obtained target proteins were standardized using the UniProt database. The disease targets of chondromalacia patellae were obtained by logging into GeneCards， PharmGkb databases. The intersection of drug targets and disease targets was then used to make a Wayne diagram.Cytoscape software was used to screen and construct "drug-active ingredient-intersection target-disease" network. The protein interaction (PPI) network was constructed using String database， and the predicted targets were analyzed by GO enrichment analysis and KEGG pathway analysis using R language. Finally， the molecular docking validation of the main active ingredients and core targets of the drug was performed by Autodock software.Results：The results showed that 188 active ingredients and 249 targets of Jingutongxiao pill in the treatment of chondromalacia patellae were screened out. The main active ingredients were quercetin， naringenin， kaempferol， luteolin， beta-sitosterol， etc. The PPI network mainly calculated out 6 key targets including AKT1， CASP8， CASP3， JUN， BCL2L1， and MYC. GO enrichment analysis involved 1458 biological processes (BP)， 19 cellular components (CC)， and 65 molecular functions (MF). KEGG pathway enrichment analysis screened out 43 pathways related to chondromalacia patellae， mainly acting on lipid and atherosclerotic signaling pathways， apoptosis signaling pathways， AGE-RAGE signaling pathways， and virus-related signaling pathways.Molecular docking results showed that the main active ingredients in the drug components could bind to representative targets and show good affinity， respectively. Conclusion： This study shows that the treatment of chondromalacia patellae with Jingutongxiao pill involves multiple signaling pathways and biological processes， and the combination of its main active ingredients kaempferol， luteolin， and quercetin with the key targets AKT1， CASP3， and MYC may be one of the important mechanisms of action.

Key words: font-size:medium, ">Network pharmacology； Molecular docking； Jingutongxiao pill；Chondromalacia patellae；Mechanism of action

中图分类号:

曹坤燕, 谭新访, 郭艳幸, 郭珈宜 , 李峰. 采用网络药理学与分子对接技术研究筋骨痛消丸治疗髌骨软化症的作用机制[J]. 中国医药导刊, 2022, 24(9): 856-865.

CAO Kunyan, TAN Xinfang, GUO Yanxing, GUO Jiayi, LI Feng. Study on Action Mechanism of Jingutongxiao Pill in the Treatment of Chondromalacia Patellae Based on Network Pharmacology and Molecular Docking[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2022, 24(9): 856-865.

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