{"title":"Exploring the mechanism of <i>Epimedium</i> in treating diabetic nephropathy based on network pharmacology and experimental validation study.","authors":"Leyu Huang, Hui Li, Ying Han","doi":"10.1007/s10616-025-00748-0","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by chronic inflammation, metabolic disturbances, and progressive renal damage. Natural perennial herb, such as <i>Epimedium</i>, has shown potential therapeutic effects on DN, but its underlying mechanisms remain unclear. This study aimed to explore the pharmacological mechanisms of <i>Epimedium</i> in the treatment of DN through network pharmacology, molecular docking, and experimental validation. Active components of <i>Epimedium</i> were identified using TCMSP and SwissTargetPrediction databases, while DN-related targets were retrieved from GeneCards, DisGeNET, OMIM, and TTD databases. Overlapping targets were analyzed via PPI network and Cytoscape's cytoHubba plugin to identify hub genes. GO and KEGG enrichment analyses were conducted to explore functional pathways. Molecular docking validated the binding affinity between key targets and active components. Finally, high-glucose-induced HK-2 cell injury models were used to verify the protective effects of <i>Epimedium</i> through RT-qPCR, western blotting, and mitochondrial function assays. A total of 224 overlapping targets were identified, with <i>AKT1, TNF, HSP90AA1</i>, and <i>SRC</i> serving as key hub genes. GO and KEGG analyses revealed significant enrichment in pathways such as the PI3K-Akt signaling pathway and lipid metabolism. Molecular docking demonstrated strong interactions between <i>Epimedium</i> components and hub targets. Experimental validation showed that <i>Epimedium</i> restored nephrin and WT1 protein levels, mitigated mitochondrial dysfunction, and reversed high-glucose-induced overexpression of key targets. <i>Epimedium</i> exerts therapeutic effects on DN through multi-target interactions, primarily via the PI3K-Akt pathway, highlighting its potential as a novel treatment for DN.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-025-00748-0.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 3","pages":"82"},"PeriodicalIF":2.0000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937453/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotechnology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-025-00748-0","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by chronic inflammation, metabolic disturbances, and progressive renal damage. Natural perennial herb, such as Epimedium, has shown potential therapeutic effects on DN, but its underlying mechanisms remain unclear. This study aimed to explore the pharmacological mechanisms of Epimedium in the treatment of DN through network pharmacology, molecular docking, and experimental validation. Active components of Epimedium were identified using TCMSP and SwissTargetPrediction databases, while DN-related targets were retrieved from GeneCards, DisGeNET, OMIM, and TTD databases. Overlapping targets were analyzed via PPI network and Cytoscape's cytoHubba plugin to identify hub genes. GO and KEGG enrichment analyses were conducted to explore functional pathways. Molecular docking validated the binding affinity between key targets and active components. Finally, high-glucose-induced HK-2 cell injury models were used to verify the protective effects of Epimedium through RT-qPCR, western blotting, and mitochondrial function assays. A total of 224 overlapping targets were identified, with AKT1, TNF, HSP90AA1, and SRC serving as key hub genes. GO and KEGG analyses revealed significant enrichment in pathways such as the PI3K-Akt signaling pathway and lipid metabolism. Molecular docking demonstrated strong interactions between Epimedium components and hub targets. Experimental validation showed that Epimedium restored nephrin and WT1 protein levels, mitigated mitochondrial dysfunction, and reversed high-glucose-induced overexpression of key targets. Epimedium exerts therapeutic effects on DN through multi-target interactions, primarily via the PI3K-Akt pathway, highlighting its potential as a novel treatment for DN.
Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00748-0.
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The scope of the Journal includes:
1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products.
2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools.
3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research.
4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy.
5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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