基于网络药理学和分子对接技术分析二味杜仲汤治疗绝经后骨质疏松的作用机制

Mechanism of Erwei Duzhong Decoction in treatment of postmenopausal osteoporosis based on network pharmacology and molecular docking technology

目的 采用网络药理学和分子对接技术分析二味杜仲汤治疗绝经后骨质疏松的作用机制。方法 通过检索文献获取二味杜仲汤包含的活性成分,并通过Swiss Target Prediction平台预测二味杜仲汤各成分作用的靶点;使用Drugbank、Genecards、OMIM、DisGeNET数据库检索绝经后骨质疏松相关靶点,将药物作用的靶点与疾病靶点进行映射得到交集基因,使用STRING数据库绘制蛋白相互作用(PPI)网络获取网络中核心靶点,通过Metascape平台进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,使用Cytoscape3.8.2构建“药物成分–靶点–通路”网络筛选核心成分,利用Vina软件对核心靶点和核心成分进行分子对接。结果 共筛选到25种有效成分,主要为牛蒿素(vulgarin)、伞形花内酯(7-hydroxycoumarin)、阿魏酸(ferulic acid)、异绿原酸(isochlorogenic acid C)、哈巴俄苷(harpagoside)等;药物与疾病共有278个靶点,核心靶点有白蛋白(ALB)、肿瘤坏死因子-α(TNF-α)、丝氨酸/苏氨酸激酶1(AKT1)、表皮生长因子受体(EGFR)、非受体酪氨酸激酶(SRC)等。二味杜仲汤涉及到的生物过程有细胞对肽的反应、细胞对激素刺激的反应、激素水平的调节、细胞对脂质的反应,KEGG富集分析得到的通路主要有癌症通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路、类固醇激素生物合成等。结论 二味杜仲汤可以通过vulgarin、7-hydroxycoumarin、ferulic acid等成分与ALB、TNF-α、AKT1、等靶点产生相互作用,调节PI3K/Akt信号通路、EGFR等通路实现治疗绝经后骨质疏松的作用。

Objective To analyze the active components of Erwei Duzhong Decoction and its mechanism of action in treatment of postmenopausal osteoporosis based on network pharmacology and molecular docking technology. Methods The active ingredients contained in Erwei Duzhong Decoction were obtained by searching literature, and the targets of Erwei Duzhong Decoction were predicted by Swiss Target Prediction platform. Drugbank, Genecards, OMIM, and DisGeNET databases were used to search for postmenopausal osteoporosis-related targets. The target of drug action was mapped to the target of disease to obtain the intersection gene. The protein interaction network was mapped using STRING database to obtain the core target in the network. Metascape platform was used for enrichment analysis of gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomics(KEGG). A drug composition-target-pathway network was constructed using Cytoscape 3.8.2 to screen core components, and Vina software was used for molecular docking of core targets and core components. Results A total of 25 active components were selected, which mainly include vulgarin,7-hydroxycoumarin, ferulic acid, isochlorogenic acid C, harpagoside, etc. There are 278 targets of drugs and diseases, and the core targets are albumin(ALB), tumor necrosis factor-α(TNF-α), Serine/threonine kinase 1(AKT1), epidermal growth factor receptor(EGFR), and non-receptor tyrosine kinase(SRC). The biological processes involved in Erwei Eucommia Decoction include cell response to peptides, cell response to hormone stimulation, hormone levels. The main pathways obtained by KEGG enrichment analysis include cancer pathway, phosphatidylinositol 3-kinase signaling pathway, and steroid hormone biosynthesis. Conclusion Erwei Duzhong Decoction can interact with ALB, TNF-α, AKT1 and other targets by vulgarin, 7-hydroxycoumarin and ferulic acid, and adjust PI3K/Akt signaling pathway, EGFR and other pathways to treat postmenopausal osteoporosis.