| 433 | 0 | 63 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 基于GEO数据库结合网络药理学、分子对接和细胞实验探讨山药改善炎症性肠病的作用机制。方法 采用网络药理学、生物信息学并结合细胞实验的方法，探讨山药改善炎症性肠病的潜在作用机制。通过TCMSP数据库筛选和预测山药的活性成分及潜在靶点，应用GEO数据库中的GSE227747数据集、GeneCards数据库收集炎症性肠病相关疾病靶点，利用韦恩图获取药物和疾病的交集靶点，通过String网站构建交集靶点的PPI网络，采用David数据库对交集靶点进行KEGG和GO富集分析，最后通过LPS诱导IEC-6细胞损伤模型进行验证。结果 从山药筛选得到71个活性成分，共有658个靶点；炎症性肠病共有10 745个潜在的治疗靶点，两者共有31个交集靶点；KEGG分析显示交集靶点主要通过调控TNF信号通路、IL-17信号通路、NF-κB信号通路等信号通路改善炎症性肠病，主要涉及炎症反应、凋亡途径和蛋白质水解等相关生物进程。细胞实验发现山药可明显改善脂多糖（lipopolysaccharide,LPS）诱导的IEC-6细胞炎症水平、增加紧密连接蛋白表达、降低肠道屏障通透性，减轻炎症性肠病。结论 山药可通过“多成分-多靶点-多途径”发挥改善炎症性肠病的作用，为阐释山药改善炎症性肠病的临床应用提供了科学依据。
Abstract：Objective To investigate the therapeutic mechanism of Dioscorea opposita Thunb.(Chinese yam,CY) in inflammatory bowel disease(IBD) by integrating GEO database analysis, network pharmacology, molecular docking, and cellular experiment validation. Methods An integrated approach combining network pharmacology,bioinformatics,and cellular experiments was employed. Active components of CY and their potential targets were identified using TCMSP database. Disease-associated targets for IBD were retrieved from the GEO database GSE227747 and the GeneCards database.Common targets between the drug and disease were identified by using Venn diagrams. A protein-protein interaction(PPI) network of the overlapping targets was constructed via the STRING platform,and functional enrichment analysis(KEGG and GO)was performed using the DAVID database. Finally,a lipopolysaccharide(LPS)-induced IEC-6 cell injury model was used for experimental validation. Results A total of 71 active components of CY corresponding to 658 targets were identified,while 10 745 potential therapeutic targets were associated with IBD. Thirty-one overlapping targets were obtained. KEGG enrichment analysis showed that these common targets are primarily involved in TNF,IL-17,and NF-κB signaling pathways,and are associated with the biological processes such as inflammation response, apoptosis, and proteolysis. Cellular experiments revealed that CY could significantly reduce inflammation in LPS-induced IEC-6 cells,increase the expression of tight junction proteins,decrease intestinal barrier permeability,and alleviate IBD-like injury. Conclusion This study suggests that CY ameliorates IBD through a ″ multicomponent,multi-target,multi-pathway″ mechanism,providing a scientific basis for its clinical application in IBD treatment.
[1]GILLILAND A,CHAN J J,DE WOLFE T J,et al. Pathobionts in inflammatory bowel disease:Origins,underlying mechanisms,and implications for clinical care[J]. Gastroenterology,2024,166(1):44-58.
[2]DIEZ-MARTIN E,HERNANDEZ-SUAREZ L,MUÑOZ-VILLAFRANCA C,et al. Inflammatory bowel disease:A comprehensive analysis of molecular bases,predictive biomarkers,diagnostic methods,and therapeutic options[J]. International Journal of Molecular Sciences,2024,25(13):7062.
[3]佚名.神农本草经[M].广州：广东科学技术出版社，2022:13.
[4]GUO Y,LIU F,ZHANG J,et al. Research progress on the structure,derivatives,pharmacological activity,and drug carrier capacity of Chinese yam polysaccharides:A review[J]. Int J Biol Macromol,2024,261(Pt2):129853.
[5]林长国.自拟通肠汤治疗粘连性肠梗阻50例[J].中国中医急症，2009,18(9):1473.
[6]高云航，李晗，李建良，等.基于网络药理学及蛋白质组学探讨优韧集胶囊改善骨质疏松的作用机制[J].中国中药杂志，2025,50(2):515-526.
[7]XIE Y,AN L,WANG X,et al. Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo:A phytochemical and pharmacological study[J]. J Ethnopharmacol,2024,333:118427.
[8]YAN S,YIN L,DONG R. Inhibition of IEC-6 cell proliferation and the mechanism of ulcerative colitis in C57BL/6 mice by dandelion root polysaccharides[J]. Foods,2023,12(20):3800.
[9]TÜLÜCE Y,KELEŞA Y,KÖSTEKCI S. Assessment of redox homeostasis via genotoxicity,cytotoxicity,apoptosis and NRF-2 in colorectal cancer cell lines after treatment withGanoderma lucidum extract[J]. Drug Chem Toxicol,2024,47(5):693-709.
[10]DE GREGORIO A,SERAFINO A,KRASNOWSKA E K,et al. Protective effect of limosilactobacillus fermentum ME-3 against the increase in paracellular permeability induced by chemotherapy or inflammatory conditions in Caco-2 cell models[J]. International Journal of Molecular Sciences,2023,24(7):6225.
[11]LI Y,LIU B,ZHAO T,et al. Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood-brain barrier permeability via regulating Caveolin-1-dependent ZO-1and Claudin-5 endocytosis in acute ischemic stroke[J]. Journal of Nanobiotechnology,2023,21(1):70.
[12]TANG X,HUANG G,ZHANG T,et al. Elucidation of colon-protective efficacy of diosgenin in experimental TNBS-induced colitis:inhibition of NF-κB/IkB-α and Bax/Caspase-1 signaling pathways[J]. Biosci Biotechnol Biochem,2020,84(9):1903-1912.
[13]YAMAKUNI T,AOKI K,NAKATANI K,et al. Garcinone B reduces prostaglandin E2 release and NF-κB-mediated transcription in C6 rat glioma cells[J]. Neuroscience Letters,2006,394(3):206-210.
[14]SAITO S,TANAKA M,SATOH-ASAHARA N,et al. Taxifolin:A potential therapeutic agent for cerebral amyloid angiopathy[J]. Front Pharmacol,2021,12:643357.
[15]HOU J,HU M,ZHANG L,et al. Dietary taxifolin protects against dextran sulfate sodium-induced colitis via NF-κB signaling,enhancing intestinal barrier and modulating gut microbiota[J]. Front Immunol,2020,11:631809.
[16]REDDY S D,SIVA B,POORNIMA B,et al. New free radical scavenging neolignans from fruits of Piper attenuatum[J]. Pharmacogn Mag,2015,11(42):235-241.
[17]MUSSAGY C U,FARIAS F O,TROPEA A,et al. Ketocarotenoids adonirubin and adonixanthin:Properties,health benefits,current technologies,and emerging challenges[J]. Food Chemistry,2024,443:138610.
基本信息:
DOI：10.16389/j.cnki.cn42-1737/n.2026.01.004
中图分类号:R285
引用信息:
[1]闫晓东,解玉军,范婉喻,等.基于GEO数据库结合网络药理学和分子对接技术探究山药改善炎症性肠病作用机制[J].江汉大学学报(自然科学版),2026,54(01):39-53.DOI:10.16389/j.cnki.cn42-1737/n.2026.01.004.
基金信息:
国家自然科学基金资助项目（81973471,82003937）