山药-黄芪药对治疗2 型糖尿病性骨质疏松的网络药理学机制研究
Network pharmacology mechanism of Dioscoreae Rhizoma and Astragali Radix in treating type 2 diabetic osteoporosis
  
DOI:10.3969/j.issn.1006-7108.2021.06.017
中文关键词:  山药-黄芪  2 型糖尿病性骨质疏松  网络药理学  作用机制  药对
英文关键词:Dioscoreae Rhizoma-Astragali Radix  type 2 diabetic osteoporosis  network pharmacology  mechanism  drug pair
基金项目:国家自然科学基金项目(81804052);广东省自然科学基金项目(2018A030313305)
作者单位
赵元1,2 李香斌3 张尚斌1,2 陈剑平,2* 1. 广州中医药大学第四临床医学院广东 深圳 518033 2. 深圳市中医院/深圳市医院中药制剂研究重点实验室广东 深圳 518033 3. 北京中医药大学深圳医院广东 深圳 518172 
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中文摘要:
      目的 筛选山药-黄芪药对的化学成分并预测其作用靶点,建立药物活性成分-作用靶点-信号通路网络,分析山药-黄芪药对治疗2 型糖尿病性骨质疏松(type 2 diabetic osteoporosis,T2DOP)的作用机制。方法 通过中药系统药理数据库和分析平台(TCMSP)检索山药、黄芪的所有潜在活性成分及其对应的作用靶点,通过GeneCards和OMIM数据库检索2 型糖尿病性骨质疏松的相关靶基因,构建山药、黄芪“化学成分-候选靶标-T2DOP相关靶标”网络,筛选节点并对节点中的靶标进行基因本体(GO)分析和京都基因与基因组百科全书( KEGG) 通路分析。最终利用Cytoscape软件绘制“化学成分-关键作用靶点-信号通路”网络。结果 筛选得到活性化合物36 个,其中山药16 个、黄芪20 个,共涉及698 个靶点,T2DOP直接相关靶基因3 305 个;筛选节点40 个,其中31 个为T2DOP相关靶基因。这些基因主要涉及56 个生物学过程,21 个分子功能,10 个细胞组分条目,作用于17 条信号通路中的关键靶点;山奈酚等13 个化合物可能为核心活性分子,CDK2等15 个靶标为核心靶标。结论 本研究结果初步阐释了山药-黄芪药对治疗T2DOP的物质基础及作用机制,体现了中药多成分、多靶点、多途径的特点,为进一步深入揭示其作用机制奠定了良好基础。
英文摘要:
      Objective The chemical constituents and action targets of Dioscoreae Rhizoma-Astragali Radix, were screened by network pharmacological method, a network of active ingredients-targets-signaling pathways was established, and the mechanism of the combination of Dioscoreae Rhizoma- Astragali Radix in the treatment of type 2 diabetic osteoporosis (T2DOP) was analyzed. Methods All potential active ingredients of Dioscoreae Rhizoma and Astragali Radix and their corresponding targets were retrieved through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the related target genes of type 2 diabetic osteoporosis were retrieved through Gene Cards and OMIM database to construct Dioscoreae Rhizoma and Astragali Radix of "chemical composition-candidate target-T2DOP related targets" network. Main nodes are screened and performed by GO and KEGG analysis; Finally, a "chemical components- key role targets-signal pathway" network was constructed by using Cytoscape software. Results 36 active compounds were screened, including 16 compounds in Dioscoreae Rhizoma and 20 compounds in Astragali Radix, a total of 698 targets. 3305 target genes were directly related to T2DOP and 40 key nodes were selected, of which 31 nodes were identified to be related to T2DOP. These genes are mainly involved in 56 biological processes, 21 molecular functions, 10 cell component entries, and these genes were acted on key targets in 17 signaling pathways; 13 compounds may be the core active molecules such as kaempferol, and 15 targets are the core targets such as CDK2. Conclusion The results of this study preliminarily explained the material basis and mechanism of action of Dioscoreae Rhizoma and Astragali Radix for the treatment of T2DOP, which reflected the characteristics of multi-components-multi-targets-multi-paths of traditional Chinese medicine, which laid a good foundation for further revealing its mechanism.
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