基于网络药理学的墨旱莲-女贞子药对“异病同治”糖尿病肾病与糖尿病视网膜病变的机制研究

Treating different disease with same method in traditional Chinese medicine: mechanisms of Eclipta alba-glossy privet fruit medicinal pair in treating diabetic nephropathy and diabetic retinopathy based on network pharmacology

关键词:  墨旱莲  女贞子  糖尿病肾病  糖尿病视网膜病变  异病同治

Key words:  Eclipta alba  glossy privet fruit  diabetic nephropathy  diabetic retinopathy  treating different disease with same method

摘要:

[目的] 通过网络药理学的方法，研究墨旱莲-女贞子药对"异病同治"糖尿病肾病（DN）与糖尿病视网膜病变（DR）的药理作用机制，验证国医大师吕仁和教授治疗DN与DR的临床经验。[方法] 利用TCMSP、TCMID和Uniprot数据库，搜集并获取墨旱莲、女贞子的化学成分及其作用靶点。利用NCBI-gene、Genecards和OMIM数据库搜集DN和DR的疾病相关靶点。通过String数据库、Cytoscape3.7.2软件、TBtools软件构建药物靶点蛋白相互作用网络，获取交集靶点。利用BioGPS数据库和Cytoscape3.7.2软件构建作用靶点-组织分布网络图，运用GO数据库和Cytoscape3.7.2软件的ClueGO插件对交集靶点进行GO和KEGG富集分析。[结果] 墨旱莲-女贞子药对主要含有14个活性成分和124个潜在作用靶点，DN相关靶点2 614个，DR相关靶点2 587个，其中药对同时作用于DN和DR的共同靶点有63个。有11个作用靶点在胰岛、视网膜和肾脏高表达，KEGG富集分析得到共同靶点主要富集在糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路和IL-17信号通路等115条通路上，涉及对含氧化合物的反应、细胞对化学刺激的反应、对脂质的反应和细胞群增殖的调节等1 686个生物过程。[结论] 墨旱莲-女贞子药对可能通过调节多个靶点、多条通路和多个生物反应过程，达到对DN与DR的"异病同治"作用，为吕仁和教授的临床经验用药提供了网络药理学验证，也为今后进一步研究墨旱莲-女贞子药对的药理作用机制提供了依据。

Abstract:

[Objective] The study aims to explore the pharmacological mechanisms of treating different disease with same method of Eclipta alba-glossy privet fruit medicinal pair in treating diabetic nephropathy(DN) and diabetic retinopathy(DR) through network pharmacology,which could validate the clinical experience of national medical master Professor LYU Renhe.[Methods] After excavating all the chemical components and medicine targets related to the Eclipta alba-glossy privet fruit medicinal pair from TCMSP,TCMID and Uniprot database,the targets of diabetic nephropathy and diabetic retinopathy were screened out through NCBI-geng,Genecards and OMIM database. Protein-protein interaction network of medicinal pair was constructed through String platform,Cytoscape software (3.7.2 version) and TBtools software;and common targets were obtained. BioGPS database and Cytoscape software were used to constructed targets-tissues network. GO database and ClueGO program in Cytoscape software were used to perform GO function enrichment analysis and KEGG pathway enrichment analysis on common targets.[Results] Totally 14 active ingredients and 124 potential targets of Eclipta alba-glossy privet fruit medicinal pair were screened out,the 2 614 and 2 587 targets were related to diabetic nephropathy and diabetic retinopathy;respectively,the 63 targets were related to treating both diabetic nephropathy and diabetic retinopathy in Eclipta alba-glossy privet fruit medicinal pair. The results of network analysis indicated that 11 targets were expressed highly in pancreatic islet,retina and kidney;the 115 pathways were regulated in treating DN and DR,including AGE-RAGE signaling pathway in diabetic complications,TNF signaling pathway,IL-17 signaling pathway,PI3K-Akt signaling pathway and HIF-1 signaling pathway;furthermore,1 686 biological response processes were enriched as well,such as oxidative stress,inflammation,and metabolism of glucose and lipid.[Conclusion] Eclipta alba-glossy privet fruit medicinal pair may regulate multiple targets,pathways and biological process in the treatment of diabetic nephropathy and diabetic retinopathy,which deciphered the clinical medication experiences of Professor LYU Renhe from the viewpoint of pharmacological network and provided further basis for understanding the pharmacological mechanisms of Eclipta alba-glossy privet fruit medicinal pair.