基于网络药理学和分子对接研究白花丹治疗骨性关节炎的分子机制

Molecular mechanism of action of Plumbago zeylanica L.in treatment of osteoarthritis: A study based on network pharmacology and molecular docking

目的:利用网络药理学与分子对接技术分析白花丹有效成分的作用靶标,探讨其治疗骨性关节炎(OA)的作用机制。方法:通过查阅文献获取白花丹相关的40种药物化学成分,利用Pubchem数据库检索获取有效成分信息,采用Swiss Target Prediction数据库筛选成分作用靶点,运用CytoScape 3.7.2软件构建白花丹有效成分-成分靶点网络。通过OMIM、GeneCards和DisGeNET数据库获取OA疾病相关的靶点。基于String数据库、Gene MANIA数据库,在CytoScape 3.7.2软件中构建蛋白相互作用(PPI)网络,其核心靶点涉白细胞介素6(IL-6)、血管内皮生长因子(VEGFA)、丝裂原活化蛋白激酶1(MAPK1)、丝裂原活化蛋白激酶8(MAPK8)、前列腺素内过氧化物合酶2(PTGS2)等。进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)的功能注释和富集分析以及反应物途径分析。结果:获得252个GO条目,71条和OA有关通路,主要涉及肿瘤、癌症中的蛋白多糖、雌激素信号通路、肿瘤坏死因子信号通路、类风湿性关节炎等以及18条反应物途径。分子对接结果显示核心成分与核心靶点能够较好地结合。结论:本文预测了白花丹治疗OA的作用机制,为进一步明确其有效成分和作用机制奠定了基础。

Objective: To investigate the mechanism of action of Plumbago zeylanica L.in the treatment of osteoarthritis by analyzing the action targets of the effective constituents of Plumbago zeylanica L.based on network pharmacology and molecular docking.Methods: Related articles were reviewed to obtain 40 chemical components associated with Plumbago zeylanica L.,and Pubchem database was used to obtain the information of effective constituents.Swiss Target Prediction database was used to screen out the action targets of the effective constituents, and CytoScape 3.7.2 software was used to construct the effective constituent-target network for Plumbago zeylanica L.OMIM,GeneCards, and DisGeNET databases were used to obtain the targets of OA.Based on String and Gene MANIA databases, CytoScape 3.7.2 software was used to construct a protein-protein interaction network, and core targets involved interleukin-6,vascular endothelial growth factor A,mitogen-activated protein kinase 1,mitogen-activated protein kinase 8,and prostaglandin-endoperoxide synthase 2.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes functional annotation and enrichment analysis were performed, as well as a reactant pathway analysis.Results: A total of 252 GO items and 71 OA-related pathways were obtained, including tumor, proteoglycan in cancer, estrogen signaling pathway, tumor necrosis factor signaling pathway, rheumatoid arthritis, and 18 reactant pathways.Molecular docking showed that the core constituents were well bound to the core targets.Conclusion: This article predicts the mechanism of action of Plumbago zeylanica L.in the treatment of OA,which lays a foundation for further clarification of its effective constituents and mechanism of action.