基于网络药理学的牛膝防治骨质疏松潜在分子机制研究

Potential Molecular Mechanisms of Puerarin in Treatment of Atherosclerosis Based on Network Pharmacology

目的通过网络药理学方法探讨牛膝防治骨质疏松(Osteoporosis)潜在的分子生物学机制。方法从文献资料及中药系统药理学分析平台(TCMSP)获取牛膝相关活性成分及靶点;通过Therapeutic Target Database、DrugBank以及DisGeNET数据库查找与Osteoporosis相关的靶点,并将牛膝及Osteoporosis靶点通过基因标准化后进行映射;利用STRING数据库筛选核心靶点,通过Cytoscape软件进行靶蛋白之间可视化分析;利用DAVID数据库对核心靶点蛋白进行GO及KEGG通路富集分析,并构建牛膝-成分-靶点-信号通路多维网络。结果共得到牛膝21个活性成分,主要成分有β-蜕皮甾酮、黄连碱、小檗碱、β-谷甾醇、黄连素、黄芩苷等;211个牛膝相关靶点,主要包括SELE、VCAM1、ICAM1、ESR1、AR、IL6、IL1B、MYC等;485个Osteoporosis相关靶点,主要包括VDR、ESR1、AR、PGR、CALCR、SOST、SHBG等。映射结果通过STRING筛选出TNF、ESR1、AR、IL6、IL1B等共35个核心靶点。GO注释分析筛选出280个生物学过程,包括对雌二醇的反应、血管内皮生长因子产生的正调控、细胞增殖的正调控、一氧化氮生物合成过程的正调控、血管生成等过程;20个细胞组分主要涉及线粒体、细胞器膜、蛋白质复合物等;50个分子功能主要包括蛋白质结合、维生素D24羟化酶活性、雌激素受体活性、血红素结合、铁离子结合等。KEGG富集分析结果有87条信号通路,主要涉及破骨细胞分化、NF-κB信号通路、MAPK信号通路、雌激素信号通路、肌萎缩侧索硬化(ALS)、造血细胞系等。结论牛膝是通过多成分、多靶点、多途径相互作用,从而达到防治骨质疏松的目的。

Objective To explore the potential molecular biological mechanism of Achyranthes bidentata preventing and treating osteoporosis by network pharmacology.Methods Byidentifying all related active ingredients and potential targets of Achyranthes bidentata from TCMSP, To retrieve Osteoporsis-related targets through TTD, DrugBank and DisGeNET databases,And standardizing all of the genes, so that mapping the targets between Achyranthes bidentata and Osteoporsis.Using STRING platform to construct PPI network and screen core targets.and using Cytoscape software to visualize the target proteins.GO classification and KEGG pathways enrichment analysis of the key target proteins was performed by DAVID database, and A multi-dimensional network of Achyranthes bidentata-ingredient-target-signal pathway was constructed.Results Twenty-one active ingredients of Achyranthes bidentata were obtained, including beta-ecdysterone, berberine, beta-sitosterol, berberine and baicalin, etc. 211 related targets of Achyranthes bidentata were obtained, including SELE, VCAM1, ICAM1, ESR1, AR, IL6, IL1 B, MYC and so on;485 related targets of Osteoporosis were obtained, including VDR, ESR1, AR, PGR, CALCR, SOST, SHBG, etc. 35 key targets such as TNF, ESR1, AR, IL6 and IL1 B were screened out by STRING. GO annotation analysis screened 280 biological processes, including response to estradiol, positive regulation of vascular endothelial growth factor production, positive regulation of cell proliferation, positive regulation of nitric oxide biosynthetic process, angiogenesis, etc.20 Cellular component information, mainly involving mitochondrion, organelle membrane, protein complex, etc. 50 Molecular function information mainly related to protein binding, vitamin D 24-hydroxylase activity, estrogen receptor activity, heme binding, iron ion binding, etc. KEGG enrichment analysis showed that 87 pathways were associated with Osteoporosis, including Osteoclast differentiation, NF-kappa B signaling pathway, MAPK signaling pathway, Estrogen signaling pathway, Amyotrophic lateral sclerosis(ALS), Hematopoietic cell lineage, etc.Conclusion Achyranthes bidentata participates in the process of therapeutic process by regulating various ingredients, targets and signaling pathways, so as to achieve the goal of treating Osteoporosis.