Table_2_Network Pharmacology-Based Investigation of the Molecular Mechanisms of the Chinese Herbal Formula Shenyi in the Treatment of Diabetic Nephropathy.XLSX

BackgroundThe Chinese herbal formula Shenyi (SY) is a prescription that was developed by the Department of Nephrology, Chinese People's Liberation Army General Hospital. This preparation is mainly used to treat chronic kidney disease (CKD) caused by Diabetic nephropathy (DN) and is effective. However, the active ingredients of SY, DN treatment-related molecular targets and the effector mechanisms are still unclear.
MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and the Traditional Chinese Medicine and Chemical Component Database of Shanghai Institute of Organic Chemistry were used to screen the active ingredients in SY, the TCMSP database and Swiss Target Prediction database were used to collect the targets of the active ingredients of SY, and the Gene Cards and Online Mendelian Inheritance in Man (OMIM) databases were used to screen for DN pathogenesis targets. The intersections of the component targets and disease targets were mapped to obtain the therapeutic targets. The METASCAPE database was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the therapeutic targets. Cytoscape 3.7.2 was used to analyze topological parameters and construct a network of SY for the treatment of DN.
ResultsSixty-two active ingredients and 497 active ingredient effector targets in SY, 3260 DN-related targets, and 271 SY treatments for DN targets were identified. Among these targets, 17 were core targets, including AKT1, tumor necrosis factor (TNF), interleukin-6 (IL6), and TP53. The GO and KEGG enrichment analyses show that SY's therapeutic effects for DN occur mainly through pathways such as advanced glycation end product (AGE)-RAGE, PI3K-Akt, and IL-17.
ConclusionMultiple active ingredients in SY exhibit treatment effects on DN by affecting metabolism, inhibiting inflammation, and affecting cell structure growth.

背景 中药方剂参芪方（Shenyi, SY）由中国人民解放军总医院肾病科研发，该制剂主要用于治疗糖尿病肾病（Diabetic nephropathy, DN）所致慢性肾脏病（Chronic kidney disease, CKD），且疗效确切。但目前参芪方的有效成分、抗糖尿病肾病相关分子靶点及作用机制尚不明确。
方法 本研究借助中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology, TCMSP）及上海有机化学研究所中药与化学成分数据库，筛选参芪方中的有效成分；通过TCMSP数据库与瑞士靶点预测（Swiss Target Prediction）数据库收集参芪方有效成分的靶点信息，并从Gene Cards数据库及人类孟德尔遗传在线（Online Mendelian Inheritance in Man, OMIM）中筛选糖尿病肾病致病靶点。将成分靶点与疾病靶点取交集，获得参芪方抗糖尿病肾病的治疗靶点。使用METASCAPE数据库对治疗靶点开展基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析；采用Cytoscape 3.7.2软件分析拓扑参数，构建参芪方治疗糖尿病肾病的调控网络。
结果 本研究共筛选得到参芪方中的62种有效成分及497个有效成分作用靶点，糖尿病肾病相关靶点共3260个，参芪方抗糖尿病肾病的治疗靶点共271个。其中核心靶点共17个，包括AKT1、肿瘤坏死因子（tumor necrosis factor, TNF）、白细胞介素-6（interleukin-6, IL6）及TP53。GO与KEGG富集分析结果显示，参芪方抗糖尿病肾病的治疗作用主要通过晚期糖基化终末产物（advanced glycation end product, AGE）-RAGE、PI3K-Akt及IL-17等通路实现。
结论 参芪方中的多种有效成分可通过调控代谢、抑制炎症反应及影响细胞结构生长等方式发挥抗糖尿病肾病的治疗作用。