基于网络药理学探讨鸡血藤在膝骨性关节炎中的作用

Study on Mechanism of Caulis spatholobi on Knee Osteoarthritis Based on Network Pharmacology

摘要: 目的：采用网络药理学研究方法，明确“鸡血藤”治疗膝骨性关节炎的药理机制。方法：通过TCMSP检索筛选鸡血藤的活性成分及靶点，并通过UniProt数据库将靶点的蛋白名转化成基因名格式，在GeneCards数据库中寻找膝骨性关节炎相关靶点，采用STRING数据库构建靶点相互作用网络图，筛选出前十靶点蛋白，采用Cytoscape 3.6.1软件绘制前十靶点蛋白图。运用Cytoscape 3.6.1软件绘制“药物活性成分–靶点–疾病”网络图，最后将共有靶点导入DAVID数据库中进行GO富集分析及KEGG富集分析。结果：共筛选出符合条件的鸡血藤化学成分23个。得到木樨草素、刺芒柄花素、β-谷甾醇、甘草查尔酮A等关键化合物。从GeneCards数据库中得到膝骨性关节炎相关靶点2101个，鸡血藤靶点与膝骨性关节炎共同靶点64个，排名前十的靶点分别为肿瘤坏死因子(TNF)、丝氨酸/苏氨酸蛋白激酶(AKT1)、白细胞介素-6 (IL-6)、细胞肿瘤抗原p53 (TP53)、信号传导及转录激活因子3 (STAT3)、基质金属蛋白酶-9 (MMP-9)、半胱氨酸蛋白酶3 (CASP3)、前列腺素G/H合成酶2 (PTGS2)、转录因子AP-1 (JUN)、白细胞介素-1β (IL-1β)。GO富集分析主要涉及RNA聚合酶所有启动子对转录的正向调控、正向调节细胞增殖、序列特异性DNA结合转录因子活性的正向调节；KEGG富集分析涉及TNF信号通路、HIF-1信号通路和PI3K-AKT通路等。结论：鸡血藤治疗KOA具有多成分、多靶点、多通路的特点。

Abstract: Objective: To investigate the pharmacological mechanism of Caulis spatholobi in the treatment of knee osteoarthritis. Methods: The active components and targets of Caulis spatholobi were screened by TCMSP retrieval, and the protein names of the targets were converted into gene names by Uni-Prot database. The targets related to knee osteoarthritis were searched in GeneCards database, the target interaction network diagram was constructed by STRING database, and the top ten target proteins were screened out. Cytoscape 3.6.1 software was used to draw the top ten target protein diagram and the network diagram of “drug active components-target-disease” was drawn by Cyto-scape 3.6.1 software. Finally, the common targets were imported into DAVID database for GO enrichment analysis and KEGG enrichment analysis. Results: A total of 23 chemical constituents of Caulis spatholobi were screened out. Key compounds such as luteolin, formononetin, β-sitosterol and glycyrrhiza chalcone A were obtained. 2101 targets related to knee osteoarthritis and 64 common targets of Caulis spatholobi and knee osteoarthritis were obtained from GeneCards database. The top 10 targets were tumor necrosis factor (TNF), serine/threonine protein kinase (AKT1), interleukin-6 (IL-6), cell tumor antigen p53 (TP53), signal transduction and transcription activator 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and cysteine proteinase 3 (CASP3), prostaglandin G/H synthase 2 (PTGS2), transcription factor AP-1 (JUN), and interleukin-1β (IL-1β). GO enrichment analysis mainly involved the positive regulation of transcription by all promoters of RNA polymer-ase, the positive regulation of cell proliferation, and the positive regulation of sequence-specific DNA-binding transcription factor activity. KEGG enrichment analysis involved TNF signaling pathway, HIF-1 signaling pathway and PI3K-Akt pathway, etc. Conclusion: Caulis spatholobi has the characteristics of multiple components, multiple targets and multiple pathways in treatment of KOA.