Table_4_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.

研究背景：中药方剂参益（Shenyi, SY）由中国人民解放军总医院肾病科研发而成。该制剂主要用于治疗由糖尿病肾病（Diabetic nephropathy, DN）引发的慢性肾脏病（Chronic kidney disease, CKD），且临床疗效确切。但目前参益的活性成分、与DN治疗相关的分子靶点及其效应机制仍未明确。
研究方法：本研究采用中药系统药理学数据库（Traditional Chinese Medicine Systems Pharmacology, TCMSP）与中国科学院上海有机化学研究所中药化学成分数据库，筛选参益中的活性成分；通过TCMSP数据库及Swiss Target Prediction数据库收集参益活性成分的作用靶点；借助Gene Cards数据库与在线人类孟德尔遗传（Online Mendelian Inheritance in Man, OMIM）数据库筛选DN发病相关靶点。将成分靶点与疾病靶点取交集，以获得治疗靶点。利用METASCAPE数据库对治疗靶点进行基因本体（Gene Ontology, GO）及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，并构建参益治疗DN的调控网络。
研究结果：本研究共筛选得到参益中的62种活性成分、497个活性成分效应靶点、3260个DN相关靶点以及271个参益治疗DN的靶点。其中包含17个核心靶点，如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，参益对DN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。
研究结论：参益中的多种活性成分可通过调控代谢、抑制炎症及影响细胞结构生长等方式发挥对DN的治疗作用。