麻黄-葛根药对治疗糖尿病周围神经病变的药理作用

Study on the Pharmacological Mechanism of Herba Ephedrae and Radix Puerariae on the Treatment of Diabetic Peripheral Neuropathy

目的:利用中药整合药理学平台及分子对接研究探讨麻黄-葛根药治疗糖尿病周围神经病变的分子机制。方法:首先在疾病靶点筛选数据库和中药系统药理学数据库与分析平台(TCMSP)检索获取与糖尿病周围神经病变(DPN)相关的靶标基因及麻黄、葛根的活性成分;然后使用Excel查重获得药物与疾病的共同靶点,使用Cytoscape绘制蛋白质-蛋白质相互作用(PPI)网络图,对共同靶点进行基因本体(GO)富集分析,通过DAVID网站进行京都基因和基因组百科全书(KEGG)通路富集分析;最后用Cytoscape软件构建“药物-活性成分-关键靶点基因”关系网络,并用Systems Dock网站进行分子对接,评估活性成分及靶点结合的稳定性。结果:麻黄-葛根药对作用于DPN的活性成分有21个,共同靶点基因138个。该药对治疗DPN富集结果主要集中于去除超氧自由基等7个功能组别中,主要富集的通路包括蛋白激酶C通路、多元醇通路等,治疗作用的靶标主要是PKC、PTGS2、Nrf2等。结论:麻黄-葛根药可能是通过对抗氧化应激及炎症反应、减缓神经髓鞘及施万细胞的损害、改善微循环等途径来治疗DPN的。

Objective:To explore the molecular mechanism of Herba Ephedrae and Radix Puerariae drug pair in the treatment of diabetic peripheral neuropathy by using the integrated pharmacology platform of traditional Chinese medicine and molecular docking research.Methods:Firstly searched the disease target screening database and TCMSP platform to obtain the related target genes of DPN,Herba Ephedrae and Radix Puerariae and the active ingredients of the latter;then use excel to checked the common targets of drugs and diseases,and used Cytoscape to draw PPI Network diagram,GO enrichment analysis of common targets,and KEGG pathway analysis through DAVID website;finally used Cytoscape software to construct a“drug-active ingredient-key target-Gene”relationship network,and use the Systems Dock website for molecular docking to evaluate the stability of active ingredients and target binding.Results:Herba Ephedrae and Radix Puerariae drug pair had 21 active ingredients that act on diabetic peripheral neuropathy,and 138 common target genes.The results of the drug′s treatment of DPN enrichment mainly focused on removal of Among the seven functional groups such as removal of superoxide radicals,the main enriched pathways included PKC signaling pathway,Polyol pathway activation,etc.The main therapeutic target is PKC,PTGS2,Nrf2,etc.Conclusion:Herba Ephedrae and Radix Puerariae may be treated by anti-oxidative stress and inflammatory response,slowing down the damage of nerve myelin and Schwann cells,and improving microcirculation.