数字中医药（英文）2022，Vol.5Issue(2)：178-188,11.DOI:10.1016/j.dcmed.2022.06.007
基于网络药理学探讨地黄治疗糖尿病肾病合并抑郁症的作用机制
Mechanisms of Dihuang (Rehmanniae Radix) in treating diabetic nephropathy complicated with depression based on network pharmacology
摘要
Abstract
Objective To predict the molecular mechanism of Dihuang (Rehmanniae Radix) in the treat-ment of diabetic nephropathy (DN) complicated with depression based on network pharma-cology. Methods The components of Dihuang (Rehmanniae Radix) were identified from the Integ-rated Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), Tra-ditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and relevant literature. The component targets were detected by combining the SwissTarget-Prediction and PubChem databases. Disease targets were collected from the Therapeutic Tar-get Database (TTD), DisGeNET, and Ensembl databases with "diabetic nephropathy" and"depression" as keywords. The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cyto-scape 3.7.2. The co-expression genes of the key targets were collected based on the COXPRES-db 7.3. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrich-ment analysis were performed for potential targets using R language. Target-component docking was verified and evaluated using Discovery Studio 4.5. Results According to the databases and literature reports, Dihuang (Rehmanniae Radix) con-tained 65 active components, and had 155 related targets for the treatment of DN complic-ated with depression. PPI screening showed that the key targets included serine/threonine protein kinase 1 (AKT1), signal transducer and activator transcription 3 (STAT3), interleukin 6 (IL-6), mitogen-activated protein kinase 1 (MAPK1), and vascular endothelial growth factor A (VEGFA), etc. GO enrichment analysis mainly involved biological processes, such as lipid metabolism, protein secretion regulation, cell homeostasis, and phosphatidylinositol 3 kinase activity. KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements, insulin resistance (IR), neurotrophin signal path, Toll-like receptor signaling pathway, relaxin signaling pathway, epidermal growth factor receptor tyr-osine kinase inhibitors (EGFR-TKIs), etc. Molecular docking showed that the target had high affinity for stachyose, manninotriose, verbascose, nigerose, etc. Conclusion Based on network parmacology, this study preliminarily predict the effects of Di-huang (Rehmanniae Radix) in treating DN complicated with depression by regulating inflam-mation, glucose metabolism, nution nerve, etc.关键词
地黄/糖尿病肾病/抑郁症/网络药理学/分子对接/异病同治/本虚标实/炎症Key words
Dihuang (Rehmanniae Radix)/Diabetic nephropathy/Depression/Network pharmacology/Molecular docking/Simultaneous treatment of different dis-eases/True deficiency with false excess pat-terns/Inflammation引用本文复制引用
雷星,王芳,陈青垚,王小平,徐杰,高亚珍,林巧红,叶祖文,ZHANG Jieyan,SI Qin..基于网络药理学探讨地黄治疗糖尿病肾病合并抑郁症的作用机制[J].数字中医药（英文）,2022,5(2):178-188,11.基金项目
National Natural Science Foundation of China(81960714),and Jiangxi University of Chinese Medicine Graduate Innovation Project(JZYC21S52). （81960714）
