菟丝子—黄芪治疗骨质疏松症的网络药理学机制研究

Network Pharmacological Mechanism Research of Herba Cuscutae-Radix Astragali in Treating Osteoporosis

【目的】运用网络药理学方法探讨菟丝子-黄芪治疗骨质疏松症的作用机制。【方法】首先采用中药系统药理学分析平台(TCMSP)和GeneCards数据库,分别筛选菟丝子、黄芪的中药活性成分,中药靶标及骨质疏松症的疾病靶标,将中药靶标一一映射到疾病靶标,得到中药-疾病靶标并构建中药-成分-疾病-靶标调控网络。其次通过构建中药-疾病靶标的蛋白互作网络和条形图,筛选核心靶标。最后将中药-疾病靶标进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,得出中药-疾病靶标涉及的功能和信号通路。【结果】筛选得到菟丝子-黄芪治疗骨质疏松症的21个有效成分和127个中药-疾病靶标,中药-疾病靶标涉及的GO功能主要包括转录激活活性、转录因子活性、辅因子结合、核受体活性、类固醇激素受体活性、RNA聚合酶Ⅱ转录因子结合、泛素样蛋白连接酶结合、类固醇结合等。中药-疾病靶标涉及的KEGG通路主要包括前列腺癌信号通路、糖尿病并发症的晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)信号通路、动脉粥样硬化信号通路、结直肠癌信号通路、乙肝信号通路、肿瘤坏死因子(TNF)信号通路、小细胞肺癌信号通路、内分泌失调信号通路、细胞凋亡信号通路、乳腺癌信号通路等。【结论】运用网络药理学研究方法可预测出菟丝子-黄芪治疗骨质疏松症的主要活性成分、功能活动和信号通路。

Objective To explore the mechanism of Herba Cuscutae-Radix Astragali for the treatment of osteoporosis by network pharmacology.Methods Firstly,traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and GeneCards database were used to screen out the active ingredients,traditional Chinese medicine(TCM)targets and disease targets.The common targets of TCM-disease was obtained by intersecting TCM targets and disease targets,and the regulatory network of TCM-ingredient-disease-target was constructed.Then,the core targets was screened by constructing the protein protein interaction(PPI)network and bar graph of TCM-disease target.Finally,gene ontology(GO)function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out for TCM-disease targets,and the functions and signal pathways related to TCM-disease target were obtained.Results Twenty-one effective ingredients and 127 TCM-disease targets were screened out for the treatment of osteoporosis.The GO functions of TCM-disease targets mainly included transcriptional activator activity,transcription factor activity,cofactor binding,nuclear receptor activity,steroid hormone receptor activity,RNA polymeraseⅡtranscription factor binding,ubiquitin-like protein ligase binding,steroid binding and so on.KEGG pathways involved in TCM-disease targets mainly included prostate cancer signaling pathway,advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE)signaling pathway in diabetic complications,atherosclerosis signaling pathway,colorectal cancer signaling pathway,hepatitis B signaling pathway,tumor necrosis factor(TNF)signaling pathway,small cell lung cancer signaling pathway,endocrine resistance signaling pathway,cell apoptosis signaling pathway,breast cancer signaling pathway and so on.Conclusion Network pharmacology may predict the main active components,functional activities and signaling pathways in Herba Cuscutae-Radix Astragali treatment for osteoporosis.