基于网络药理学的藤黄健骨胶囊治疗骨质疏松症作用机制研究

Material Basis and Mechanism of Tenghuang Jiangu Capsule in Treatment of Osteoporosis Based on Network Pharmacology

目的采用网络药理学研究藤黄健骨胶囊治疗骨质疏松症的有效活性成分及主要作用机制。方法采用TCMSP、Uniport、DrugBank数据库检索藤黄健骨胶囊的主要化学成分及作用靶点;基于DisGeNET、DrugBank、OMIM及Genecards数据库获取骨质疏松症的相关靶点;将藤黄健骨胶囊与骨质疏松症的靶点取交集,获取藤黄健骨胶囊治疗骨质疏松症的直接靶点;利用STRING数据库得到蛋白相互作用(PPI)关系;使用DAVID数据库进行GO和KEGG富集分析;采用Cytoscape 3.7.2软件构建PPI网络、"药物-活性成分-靶点"网络以及"活性成分-重要靶点-关键通路"网络,并进行相关网络分析。结果本研究初步筛选藤黄健骨胶囊69个成分和257个靶点;骨质疏松症4547个靶点,药物-疾病交集靶点178个;经过PPI、GO、KEGG及相关网络分析,最终得到药物的主要药效成分有槲皮素、木犀草素、山奈酚、β-谷甾醇、芒柄花黄素、淫羊藿苷元等;关键靶点为ESR2、PIK3CG、PPARG、CASP3、AKT1、MAPK1、JUN、TNF、ESR1等;映射的靶标通路为PI3K-Akt信号通路、MAPK信号通路、雌激素信号通路、胰岛素信号通路、钙信号通路、破骨细胞分化等;涉及的生物过程主要有细胞增殖分化、细胞凋亡调节、雌激素反应、血管收缩调节、炎症级联反应等。结论藤黄健骨胶囊主要通过抑制炎症反应、激素调节及钙调节等途径,起到抗骨质疏松的作用,该研究为进一步的药理实验研究奠定了基础,也为骨质疏松症靶点药物的开发提供了科学理论依据。

Objective To explore the material basis and mechanism of Tenghuang Jiangu capsule in the treatment of osteoporosis by using network pharmacology.Methods The main chemical components and targets of Tenghuang Jiangu capsules were searched through TCMSP,Uniport and DrugBank databases.Obtain the relevant targets of osteoporosis through DisGeNET,DrugBank,OMIM and Genecards databases.The target of Tenghuang Jiangu capsule and the target of osteoporosis were crossed to obtain the direct target of Tenghuang Jiangu capsule in the treatment of osteoporosis.Use the STRING database to get the protein-protein interaction(PPI)relationship.The DAVID database was used for GO and KEGG enrichment analysis.Cytoscape 3.7.2 software was used to construct PPI network,"medicine-active component-target"network and"active component-important target-critical pathway"network.Perform relevant network analysis.Results The Tenghuang Jiangu capsule had 69 components and 257 targets.There were 4547 targets for osteoporosis and 178 targets for drug-disease intersection.Through PPI,GO,KEGG and related network analysis,the main pharmacodynamic components of the drug were obtained,including quercetin,luteolin,kaempferol,beta-sitosterol,formononetin,icariin,etc.The key targets were ESR2,PIK3 CG,PPARG,CASP3,AKT1,MAPK1,JUN,TNF,ESR1,etc.The key pathways were PI3 K-Akt,MAPK,estrogen,insulin,calcium,osteoclast differentiation,etc.The biological processes involved mainly include response to estradiol,apoptosis regulation,cell proliferation and differentiation,inflammatory cascade reaction,vasoconstriction regulation,etc.Conclusion The treatment of osteoporosis with Tenghuang Jiangu capsule is mainly through inhibiting inflammatory response,hormone regulation and calcium regulation.This study lays a foundation for further pharmacological experiments and provide a scientific theoretical basis for the development of osteoporosis target drugs.