基于网络药理学和分子对接技术分析六味地黄丸治疗骨质疏松症的作用机制

Study on the mechanism of Liuwei Dihuang Pills in the treatment of osteoporosis based on network pharmacology and molecular docking

基于网络药理学和分子对接技术分析六味地黄丸治疗骨质疏松症(osteoporosis,OP)的作用机制。通过TCMSP数据库进行六味地黄丸潜在化学成分获取和靶点预测,运用TTD、Disgenet、GeneCards数据库预测筛选与骨质疏松症相关的基因,利用Cytoscape 3.7.0软件建立中药-化合物-靶点-疾病可视化网络,借助String数据平台进行蛋白互作网络构建,运用Metascape数据库进行GO及KEGG作用通路分析。利用AutoDock 4.2.6软件对筛选所得化学成分与核心靶点进行分子对接验证。结果表明:六味地黄丸治疗骨质疏松症的有效成分69个,靶点125个,潜在有效成分主要包括槲皮素、豆甾醇、山柰酚、薯蓣皂苷元等,核心靶点有AKT1、IL6、VEGFA、TP53、TNF等32个;六味地黄丸通过关键靶点活化缺氧诱导因子1信号通路(HIF-1)、肿瘤坏死因子(TNF)信号通路、磷酸肌醇3激酶(PI3k-Akt)信号通路、Toll样受体信号通路等通路,涉及RNA聚合酶Ⅱ启动子转录的调控以及细胞凋亡的调控,细胞对缺氧、脂多糖、肿瘤坏死因子的反应、炎症应答等生物过程来治疗OP。分子对接结果显示,槲皮素、谷甾醇、山柰酚等与AKT1、TP53、IL6等关键靶点有着较好的结合活性。六味地黄丸通过调节骨代谢、调控炎症反应、细胞增殖分化等来预防和治疗OP,具有多成分、多靶点、多通路的作用特征,为进一步的基础研究及临床应用提供了新的思路和线索。

To analyze the mechanism of Liuwei Dihuang Pills in treating osteoporosis(OP)based on the network pharmacology and molecular docking.The acquisition of potential chemical component and target prediction of Liuwei Dihuang Pills was carried out through the TCMSP database.TTD,Disgenet,and GeneCards database were adopted to forecast and filtrate the gene related to osteoporosis,and Cytoscape 3.7.0 software was used to build TCM-chemical compound-targets-disease visualization network.The construction of protein interaction network was carried out in virtue of the String data platform,and Metascape database was used to analyze the role access of GO and KEGG.Finally,the AutoDock4.2.6 software was used to verify the molecular docking between the selected chemical component and the core target spots.In the end,the results showed that the effective constituents of Liuwei Dihuang Pills in treating the osteoporosis are 69,the target spots are 125;the potential effective constituents mainly include quercetin,stigmasterol,kaempferol,diosgenin,etc.,and there are 32 core targes,such as AKT1,IL6,VEGFA,TP53,TNF,etc.;Liuwei Dihuang Pills activates hypoxia-inducible factor 1 signaling pathway(HIF-1),tumor necrosis factor(TNF)signaling pathway,phosphatidylinositol-3 kinase(PI3k-Akt)signaling pathway,Toll-like receptors signaling pathway and other signaling pathways through the key target spots,which involve the adjustment and control of RNA polymerase Ⅱ promoter transcription and the cell apoptosis,the response and inflammatory response of cells to oxygen deficit,lipopolysaccharide,tumor necrosis factor,and other biological processes,to treat OP.The results of molecular docking show that quercetin,sitosterol and kaempferol,etc.have good binding activity with the key target spots such as AKT1,TP53 and IL6,etc.Liuwei Dihuang Pills prevents and treats OP by adjusting the bone metabolism,inflammatory response,cell proliferation and differentiation,etc.It has the characteristics of multi-component,multiple-targets and muti-pathway,which provide the new mentalities and threads for the further fundamental research and clinical application.