基于网络药理学研究梅花入骨丹治疗骨性关节炎的潜在靶点和作用机制

Potential Targets and Mechanism of Meihua Rugu Dan in Treating Osteoarthritis Based on Network Pharmacology

目的采用网络药理学和生物信息学方法探讨中药梅花入骨丹治疗骨性关节炎的主要成分、潜在作用靶点和作用机制。方法收集获取梅花入骨丹化学成分及SDF结构,利用Swiss ADME和Swiss Target Prediction数据库筛选其有效活性成分并预测其作用靶点;通过GeneCards、OMIM、TTD数据库检索骨性关节炎发病相关基因,应用Venny 2.1.0构建梅花入骨丹治疗骨性关节炎作用靶点;应用Cytoscape 3.7.2软件构建药物-成分-靶点-疾病调控网络;通过STRING构建PPI网络图并进行拓扑及聚类分析,筛选核心靶点;将药物-疾病关键靶点蛋白进行KEGG通路富集分析。结果梅花入骨丹治疗骨性关节炎的主要活性成分为黄酮类和槲皮素,AKT、VEGFA、RELA、TNF、STAT3、MARK、MMPs、TLR4是梅花入骨丹治疗骨性关节炎的关键靶点,蛋白聚糖与肿瘤、PI3K-Akt、MARK、IL-17、TNF和Toll样受体介导的信号通路是梅花入骨丹治疗骨性关节炎的主要机制通路。结论梅花入骨丹可以通过多成分、多靶点、多通路机制协同治疗骨性关节炎。

OBJECTIVE To explore the main components,potential targets,and mechanism of traditional Chinese medicine Meihua Rugu Dan in treating osteoarthritis with network pharmacology and bioinformatics.METHODS The chemical components combined with SDF structures of Meihua Rugu Dan were collected and obtained,and the Swiss ADME database and Swiss Target Prediction database were used to screen the effective active components and their targets.The genes related to osteoarthritis were collected through GeneCards,OMIM and TTD databases,and then the targets of Meihua Rugu Dan for the treatment of osteoarthritis were constructed using Venny 2.1.0 software.The Cytoscape 3.7.1 software was used to build a drug-component-target-disease regulation network.The STRING database was used to construct the PPI network diagram,and then the topological analysis and cluster analysis were performed to screen core targets.Finally,the drug-disease target proteins were analyzed for KEGG pathway enrichment.RESULTS It showed that flavonoids and quercetin are the main active ingredients of Meihua Rugu Dan for the treatment of osteoarthritis.AKT,VEGFA,RELA,TNF,STAT3,MARK,MMPs and TLR4 were showed to be the key targets of Meihua Rugu Dan in treating osteoarthritis.The analysis of KEGG pathway enrichment showed that proteoglycans and tumors,PI3 K-Akt,MARK,IL-17,TNF and Toll-like receptor signaling pathways may be the main mechanism pathways for Meihua Rugu Dan in the treatment of osteoarthritis.CONCLUSION Meihua Rugu Dan can treat osteoarthritis through multiple components,multiple targets and multiple pathways.