基于网络药理学研究鸡血藤治疗骨质疏松的分子作用机制

Study on the Molecular Mechanism of Jixueteng in the Treatment of Osteoporosis Based on Network Pharmacology

目的预测鸡血藤在治疗骨质疏松症(osteoporosis,OP)的主要活性成分的作用靶点,来探究其多成分-多靶点-多通路的作用机制。方法借助中药系统药理学分析平台(TCMSP)检索鸡血藤的化学成分及作用靶点。借助GeneCards、 NCBI等数据库检索OP相关基因。应用STRING数据库构建蛋白质相互作用关系网络,并进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,应用cytoscape3.8.0中进行中药-成分-疾病-通路-靶点网络图的绘制,并针对关键靶点进行分子对接以验证结果的可靠性。结果化合物靶点关系网络包括24个化合物和对应的88个靶点,其中涉及关键靶点包括ATK1、VEGFA、IL-6、MAPK1等。GO功能富集分析得到1937条生物过程,113项分子功能相关,62项细胞组成相关。在KEGG通路富集筛选得到144条信号通路。分子对接结果显示,筛选出的潜在活性成分与关键靶点之间具有较高的结合活性。结论鸡血藤中活性成分主要通过ATK1、VEGFA、IL-6、MAPK1等靶点调节相关通路来治疗骨质疏松,研究体现了鸡血藤"多成分-多靶点-多途径"的作用特点,为鸡血藤临床应用和进一步开发提供了科学依据。

Objective To predict the targets of the main active components of Caulis spatholobi in the treatment of osteoporosis(OP),to explore the mechanism of its multi-component,multi-target,multi-pathway.Methods With the aid of the TCM System Pharmacology Analysis Platform(TCMSP),the chemical constituents and targets of Caulis spatholobi were searched.Search OP related genes with the help of GeneCards,NCBI and other-databases.Use STRING database to construct protein interaction relationship network,and perform gene ontology(GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genome(KEGG) pathway enrichment analysis,apply cytoscape 3.8.0 for traditional Chinese medicine-components-disease-Draw the path-target network diagram,and conduct molecular docking for key targets to verify the reliability of the results.Results The compound target relationship network includes 24 compounds and corresponding 88 targets.The key targets involved include ATK1,VEGFA,IL-6,MAPK1,etc.GO function enrichment analysis revealed 1937 biological processes,113 molecular functions related,and 62 cell composition related.144 signal pathways were obtained through enrichment and screening of KEGG pathway.The results of molecular docking show that the potential active ingredients screened out have high binding activity with key targets.Conclusion The active components of Caulis spatholobi mainly regulate pathways through ATK1,VEGFA,IL-6,MAPK1 and other targets to treat osteoporosis.The research reflects the multi-component,multi-target,multi-pathway of Caulis spatholobi.The function characteristics provide a scientific basis for the clinical application and further-development of Caulis spatholobi.