红花治疗糖尿病肾病网络药理学研究

Network Pharmacology Study of Honghua in the Treatment of Diabetic Nephropathy

目的预测红花治疗糖尿病肾病的主要活性成分及作用靶点,探究其多成分-多靶点-多通路的作用机制。方法借助中药系统药理学数据库与分析平台(TCMSP)检索红花的化学成分及作用靶点,用Genecards数据库检索糖尿病肾病相关基因,应用Cytoscape 3.7.2构建可视化网络,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。结果采用TCMSP数据库从红花中选出22个主要活性成分,并预测获得103个靶点。从疾病靶点数据库筛选出糖尿病肾病相关疾病靶点2572个,通过在线韦恩图获得红花潜在治疗糖尿病肾病作用靶点共68个,进而筛选出红花治疗糖尿病肾病的有效活性成分共14个,构建了"药物-活性成分-靶点-疾病"网络,该网络中有6个化合物能与10个及以上靶点发生相互作用。KEGG通路富集分析的结果发现68个作用靶点主要参与调控细胞流体切应力与动脉粥样硬化(Fluid shear stress and atherosclerosis)、糖尿病并发症中的AGERAGE信号通路(AGE-RAGE signaling pathway in diabetic complications)、卡波西氏肉瘤相关疱疹病毒感染(Kaposi sarcoma-associated herpesvirus infection)、癌症中蛋白聚糖(Proteoglycans in cancer)、人巨细胞病毒感染(Human cytomegalovirus infection)、细胞凋亡(Apoptosis)等信号通路,富集群还包括乙型肝炎等疾病,同时前列腺癌、大肠癌等癌症相关信号通路也被显著富集。结论红花有效活性成分可能通过参与调控血浆黏稠程度、血清总胆固醇等血液流变学保护肾脏,通过细胞凋亡能够将大量的增生细胞给予有效清除,进而对肾脏功能给予有效保护,通过调节糖尿病并发症中的AGE-RAGE信号通路等信号通路治疗糖尿病肾病等,有望对中药防治糖尿病肾病提供新的证据和研究思路。

Objective To predict the action targets of the main active ingredients of Honghua in the treatment of diabetic nephropathy(DN),and to explore its multi-component-multi-target-multipath mechanism of action. Methods The chemical composition and target of Honghua were retrieved by TCMSP,genes related to diabetic nephropathy were retrieved by Genecards database,a visual network was constructed using Cytoscape 3.7.2,and GO and KEGG pathway enrichment analysis were performed. Results TCMSP database was used to select 22 main active ingredients from Honghua,and 103 targets were predicted to be obtained. 2572 targets for diabetic nephropathy-related diseases were screened from the disease target database. A total of 68 Honghua potential therapeutic targets for diabetic nephropathy were obtained through online Venn diagrams,and a total of 14 active ingredients for Honghua for diabetic nephropathy were selected a"drug-active ingredient-target-disease"network has been constructed,in which 6 compounds can interact with 10 or more targets. The results of KEGG pathway enrichment analysis found that 68 action targets are mainly involved in regulating fluid shear stress and atherosclerosis,and AGE-RAGE signaling pathway in diabetes complications,Kaposi sarcomaassociated herpesvirus infection,proteoglycans in cancer,human cytomegalovirus infection,apoptosis ect. The rich cluster also includes diseases such as hepatitis B,and cancer-related signal pathways such as prostate cancer and colorectal cancer have also been significantly enriched. Conclusion Honghua active ingredient may protect the kidney by participating in the regulation of blood viscosity such as plasma viscosity,total serum cholesterol,etc.,and a large number of proliferative cells can be effectively eliminated through apoptosis,which can effectively protect kidney function and regulate diabetes signal pathways such as AGE-RAGE signaling pathway in the treatment of diabetic nephropathy. It is expected to provide new evidence and research ideas for the prevention and treatment of diabetic nephropathy by Chinese medicine.