基于网络药理学的中药复方参芪益肾方治疗糖尿病肾病分子机制的研究
Network Pharmacology-Based Investigation of the Molecular Mechanisms of the Chinese Herbal Formula Shenyi in the Treatment of Diabetic Nephropathy.
作者信息
Chen Keng, Deng Yiyao, Shang Shunlai, Li Ping, Liu Linchang, Chen Xiangmei
机构信息
Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, China.
First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.
出版信息
Front Med (Lausanne). 2022 Jun 10;9:898624. doi: 10.3389/fmed.2022.898624. eCollection 2022.
BACKGROUND
The 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.
METHODS
The 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.
RESULTS
Sixty-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.
CONCLUSION
Multiple active ingredients in SY exhibit treatment effects on DN by affecting metabolism, inhibiting inflammation, and affecting cell structure growth.
背景
中药复方肾益（SY）是中国人民解放军总医院肾病科研发的方剂。该制剂主要用于治疗糖尿病肾病（DN）引起的慢性肾脏病（CKD），且疗效显著。然而，SY的活性成分、与DN治疗相关的分子靶点及作用机制仍不明确。
方法
利用中药系统药理学（TCMSP）数据库和上海有机化学研究所中药与化学成分数据库筛选SY中的活性成分，使用TCMSP数据库和瑞士靶点预测数据库收集SY活性成分的靶点，并利用基因卡片和人类孟德尔遗传在线（OMIM）数据库筛选DN发病机制靶点。将成分靶点与疾病靶点的交集进行映射以获得治疗靶点。利用METASCAPE数据库对治疗靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。使用Cytoscape 3.7.2分析拓扑参数并构建SY治疗DN的网络。
结果
确定了SY中的62种活性成分和497个活性成分效应靶点、3260个与DN相关的靶点以及271个SY治疗DN的靶点。在这些靶点中，17个为核心靶点，包括AKT1、肿瘤坏死因子（TNF）、白细胞介素-6（IL6）和TP53。GO和KEGG富集分析表明，SY对DN的治疗作用主要通过晚期糖基化终产物（AGE）-RAGE、PI3K-Akt和IL-17等途径实现。
结论
SY中的多种活性成分通过影响代谢、抑制炎症和影响细胞结构生长对DN发挥治疗作用。
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