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基于网络药理学和分子对接技术探讨恒古骨伤愈合剂促进骨折愈合的作用机制
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Abstract:
目的：采用网络药理学以及分子对接技术分析恒古骨伤愈合剂促进骨折愈合的机制。方法：通过检索TCMSP等数据库获得恒古的主要化合物成分和靶点及疾病靶点。将药物和疾病共有靶点制作成韦恩图，建立PPI网络，对PPI网络进行拓扑分析，MC0DE版块进行聚类分析，筛选出核心基因。构建成分–疾病–靶点网络图。使用R4.0.3软件进行GO功能富集和KEGG信号通路富集分析，之后构建成分–疾病–通路–靶点网络。采用AutoDockTools 1.5.7软件将关键活性成分和核心靶点进行分子对接，运用PyMOL对对接结果进行可视化。结果：获得恒古相关药物化合物成分106个，相关靶点946个；骨折愈合靶点2519个，疾病和药物共有靶点164个。PPI网络中有164个节点，3347条边。拓扑分析总共筛选出个82关键靶点。MCODE聚类分析总共得到6个基因簇和5个核心基因，成分–疾病靶点拓扑分析筛选出5个关键成分。GO富集总共富集到2474条生物过程，160项分子功能相关，91项细胞组成相关。KEGG通路富集总共富集到168条信号通路。分子对接结果显示，恒古的活性成分与骨折愈合的靶点基因有着很好的结合作用。结论：恒古骨伤愈合剂促进骨折愈合具有多通路、多成分、多靶点、多机制的特点。
Objective: To analyze the mechanism of Osteoking promoting fracture healing by network pharmacology and molecular docking technology. Methods: By searching TCMSP, Batman-TCM, NCBI and other databases, the main compounds, targets and disease targets of Osteoking were obtained. The selected common targets of drugs and diseases were made into Wayne diagram, and then imported into STRING database to obtain PPI network. The PPI network was imported into Cystoscape3.8.0, and the Network Analyzer tool was used for topology analysis, and MC0DE was used for cluster analysis to screen out the core genes and construct the component-disease-target network diagram. AutoDockTools1.5.7 software was used to make molecular docking between key active ingredients and core targets, and PyMOL was used to visualize the docking results. Results: 106 components and 946 related targets of Osteoking related drugs were obtained. There are 2519 targets for fracture healing, and 164 targets for diseases and drugs. There are 164 nodes and 3347 edges in PPI network. A total of 82 key targets were selected by topological analysis. A total of 6 gene clusters and 5 core genes were obtained by MCODE cluster analysis, and 5 key components were selected by component-disease target topology analysis. GO enriched a total of 2474 biological processes, 160 related to molecular functions and 91 related to cell composition. KEGG pathway is enriched to a total of 168 signal pathways. The results of molecular docking show that the core target protein has a strong binding ability with the corresponding main components, which indicates that the active components of Osteoking have a good binding effect with the target genes of fracture healing. Conclusion: Osteoking has the characteristics of multi-pathway, multi-component, multi-target and multi-mechanism in promoting fracture healing.
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