基于网络药理学的续断-补骨脂药对治疗骨关节炎作用机制研究

Study on Osteoarthritis Mechanisms of Couplet Medicine of Dipsaci Radix-Psoraleae Fructus Based on Network Pharmacology

关键词:  网络药理学  骨关节炎  续断  补骨脂  药对  靶蛋白相互作用

Key words:  network pharmacology  osteoarthritis  Dipsaci Radix  Psoraleae Fructus  couplet medicine  target protein interaction

摘要:

目的 基于网络药理学研究续断-补骨脂药对治疗骨关节炎的分子作用机制。方法 采用中药系统药理学分析平台（TCMSP）等数据库寻找与续断-补骨脂药对相关的所有化学成分以及靶点；利用OMIM数据库、DrugBank数据库以及GeneCards数据库查找与骨关节炎相关的靶点。通过Cytoscpae 3.7.1软件构建续断-补骨脂药对主要化学成分-潜在靶点网络。将续断、补骨脂以及续断-补骨脂药对治疗的潜在靶点与疾病靶点在相互作用基因/蛋白搜索工具平台STRING V10.5分别构建其蛋白-蛋白相互作用（PPI）网络。应用网络拓扑参数筛选出药物治疗疾病的关键靶点，并采用R中的Clusterprolifer对关键靶点进行Gene Ontology （GO）分析和KEGG通路富集分析。结果 选择口服利用度≥ 30%作为化合物分子的筛选条件，并通过文献挖掘进行补充，共筛选出续断-补骨脂药对的20个潜在活性成分和473个潜在靶点；通过度、介质中心度、接近度等网络拓扑特征参数评价筛选出与续断-补骨脂药对治疗骨关节炎相互作用的关键靶点19个，GO分析包含121条富集结果，其中生物过程67条，分子功能45条，细胞组件9条；得到KEGG富集通路89条。结论 续断-补骨脂药对与单味药材相比，具有更多成分，更多途径，更多靶点协同作用的特点，为后续从续断-补骨脂药对中开发出治疗骨关节炎的新药提供依据。

Abstract:

OBJECTIVE To study the molecular mechanism of couple medicine of Dipsaci Radix-Psoraleae Fructus for the treatment of osteroarthrits(OA) based on network pharmacology. METHODS The Chinese Medicine System Pharmacology Analysis Platform(TCMSP) was used to search for all chemical constituents and related targets. The OMIM database, DrugBank database and GeneCards database were used to find OA-related targets. The bioactive compound-target network was established by Cytoscape 3.7.1 software. The screened targets were used to construct the protein-protein interaction(PPI) network of Dipsaci Radix, Psoraleae Fructus and couple medicine of Dipsaci Radix-Psoraleae Fructus treating OA on the STRING V10.5 platform. The network topological parameters were used to screen out the hub genes and Clusterprolifer in R was employed to perform Gene Ontology(GO) analysis and KEGG pathway enrichment analysis on hub targets. RESULTS Used the oral bioavailability ≥ 30% as screening condition for the compounds, combined with supplement literatures searched, 20 active components and 473 corresponding potential targets of couplet medicine of Dipsaci Radix-Psoraleae Fructus. The network topological characteristic parameters, such as Degree, Betweenness, and Closeness were used to screen out 19 hub targets for the treatment of OA. A total of 121 enrichment results were obtained from 19 hub genes of couplet medicine of Dipsaci Radix-Psoraleae Fructus in OA, included 67 biological processes, 45 molecular functions, and 9 cell compositions. The hub genes were enriched by KEGG and 89 pathways played an important role in OA were screen out. CONCLUSION Compared with the signle traditional Chinese medicine, the synergetic effect of couplet medicine of Dipsaci Radix-Psoraleae Fructus with more multi-component, more multi-target, more multi-pathway is confirmed by network pharmacology, which lay a foundation for developing a new drug for the treatment of OA from the couplet medicine of Dipsaci Radix-Psoraleae Fructus.