基于网络药理学与分子对接探究桃红四物汤治疗糖尿病周围神经病变作用机制

Study on the Mechanism of Taohong Siwu Decoction(桃红四物汤)in the Treatment of Diabetic Peripheral Neuropathy Based on Network Pharmacology and Molecular Docking

目的探索桃红四物汤治疗糖尿病周围神经病变的作用机制。方法对桃红四物汤6味中药主要化学成分和作用的靶点进行检索,通过GeneCards、人类在线孟德尔遗传(OMIM)、治疗靶点(TTD)、PharmGkb、DrugBank5个数据库找出糖尿病周围神经病变相关靶点。取药物与疾病的共同靶点绘制韦恩图。利用Cytoscape构建药物-活性成分-核心靶点网络,在STRING数据库构建蛋白相互作用(protein protein interaction,PPI)网络并筛选出核心靶点,运用R软件进行基因本体(gene ontology,GO)功能注释、京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。运行AutoDock Vina进行分子对接,对接结果用Pymol显示。结果得到桃红四物汤治疗糖尿病周围神经病变的有效化合物成分44个,靶点208个,交集基因131个。GO分析得到生物过程(BP)2433个结果,细胞组成(CC)81个结果,分子功能(MF)181个结果。KEGG结果显示,桃红四物汤活性成分可能通过参与调节晚期糖基化终末产物及其受体(AGE-RAGE)、液体剪切应力和动脉粥样硬化、白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)、丝裂原活化蛋白激酶(MAPK)等信号通路发挥对糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)的治疗作用。分子对接结果显示核心化合物槲皮素、β-谷甾醇与核心靶点有较好的结合力。结论本研究挖掘桃红四物汤治疗糖尿病周围神经病变的作用机制,为后续研究提供新的理论依据。

Objective Explore the mechanism of Taohong Siwu Decoction(桃红四物汤)in the prevention and treatment of diabetic peripheral neuropathy.Methods To search the main chemical components and targets of Taohong Siwu Decoction,and find out the related targets of diabetic peripheral neuropathy by GeneCards,OMIM,TTD,PharmGkb and DrugBank.Take the common target of drugs and diseases and draw the Wayne map.The drug active ingredient core target network was constructed by using Cytoscape.PPI network was constructed in string database and the core target was screened.GO annotation and KEGG pathway enrichment analysis were performed by R software.Run autodock Vina for molecular docking,and the docking results are displayed in Pymol.Results The results showed that there were 44 effective compounds,208 targets and 131 cross genes in the treatment of diabetic peripheral neuropathy with Taohong Siwu Decoction.Go analysis obtained 2433 results of BPs,81 results of CCS and 181 results of MFS.KEGG results showed that Taohong Siwu Decoction may play a role in the treatment of DPN by regulating AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,IL-17 signaling pathway,tumor necrosis factor signaling pathway,MAPK and other signaling pathways.Molecular docking results showed that the core compounds quercetin andβ-sitosterol had good binding ability with the core target.Conclusion This study explores the mechanism of Taohong Siwu Decoction in the treatment of diabetic peripheral neuropathy,and provides a new theoretical basis for the follow-up study.