中药新药与临床药理2025，Vol.36Issue(11)：1877-1891,15.DOI:10.19378/j.issn.1003-9783.2025.11.007
基于网络医学策略研究健脾化瘀解毒方干预胃癌前病变衰老表型的作用机制
Investigating the Mechanism of Jianpi Huayu Jiedu Formula in Modulating the Senescence Phenotype of Gastric Precancerous Lesions Using a Network Medicine Strategy
摘要
Abstract
Objective To employ an integrated network medicine strategy combining bioinformatics,network pharmacology,network proximity analysis,and molecular docking to elucidate the mechanism of Jianpi Huayu Jiedu Formula(JPHYJDF)in intervening in the senescence phenotype of gastric precancerous lesions(GPL).Methods Bioinformatics analysis was performed on GPL senescence-related gene data from the GEO database.Key genes associated with GPL senescence were identified through differential expression genes(DEGs)analysis,weighted gene co-expression network analysis(WGCNA),database screening,protein-protein interaction(PPI)network construction,Gene Ontology(GO)functional annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,and gene set enrichment analysis(GSEA).Network pharmacology and network proximity methods were further applied to screen potential active components of JPHYJDF and their corresponding targets,followed by molecular docking validation.Results(1)Differential gene expression analysis of the GSE130823 dataset identified 519 DEGs related to GPL senescence.WGCNA analysis revealed 50 gene modules associated with GPL senescence,while database screening yielded 76 potential senescence-related gene targets.PPI network analysis identified key genes,including TP53,HIF1A,STAT3,CDK1,AURKA,BIRC5,and CCNB1.GO and KEGG enrichment analyses demonstrated that these genes primarily participate in cell cycle regulation,DNA damage repair,and senescence-related processes.(2)Network pharmacology analysis identified 608 potential targets of JPHYJDF's active components,80 GPL senescence-related targets,and 19 potential interaction targets.Seven core active components of JPHYJDF were identified,with ATM,CDK1,and PARP1 serving as central targets.JPHYJDF's intervention in GPL senescence primarily involved GO biological processes such as cellular oxidative stress response,telomere maintenance,negative regulation of the cell cycle,cell division,and inflammatory response,with significant associations to the p53 signaling pathway and apoptosis-related pathways.Network proximity analysis screened 23 potential active components,including quercetin,kaempferol,soy isoflavones,β-sitosterol,and stigmasterol.Molecular docking confirmed strong binding affinity and stability between these active components and key targets(ATM,ESR1,CDK1,HIF1A,PARP1,SRC).Conclusion JPHYJDF exerts anti-senescence effects in GPL through a multi-component,multi-target mechanism,modulating the p53 signaling pathway,apoptosis,and DNA damage repair pathways.This study provides novel insights into the precision treatment of GPL.关键词
胃癌前病变/衰老/健脾化瘀解毒方/生物信息学分析/网络药理学/网络医学策略Key words
gastric precancerous lesions/senescence/Jianpi Huayu Jiedu Formula/bioinformatics analysis/network pharmacology/network medicine strategy分类
医药卫生引用本文复制引用
欧嘉胤,李佳雨,方淑环,潘华峰,赵心怡,高铭均,方坚松,郑琴娟,樊湘珍,李思怡,崔永超,司徒俊鹏..基于网络医学策略研究健脾化瘀解毒方干预胃癌前病变衰老表型的作用机制[J].中药新药与临床药理,2025,36(11):1877-1891,15.基金项目
国家自然科学基金面上项目(82174319) （82174319）
癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项(2024ZD0521000) （2024ZD0521000）
广东省中医药局重点研究室研究项目(20215005) （20215005）
广东省科技创新战略专项资金项目(pdjh2024a098) （pdjh2024a098）
广东省中医药局科研项目(20231253) （20231253）
广州市卫生健康委员会基础与应用基础研究项目(SL2022A03J00189) （SL2022A03J00189）
广州中医药大学"揭榜挂帅"研究生创新专项(D-2-10) （D-2-10）
2024年校级大学生创新创业计划项目(202410572104 （）
202410572034). （）
