南方医科大学学报2024，Vol.44Issue(8)：1485-1496,12.DOI:10.12122/j.issn.1673-4254.2024.08.07
隔山消治疗溃疡性结肠炎的机制:基于UPLC-QE-MS、网络药理学及代谢组学技术
Therapeutic mechanism of Cynanchum wilfordii for ulcerative colitis:an analysis using UPLC-QE-MS,network pharmacology and metabolomics
摘要
Abstract
Objective To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis(UC).Methods UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract,and their targets were screened using public databases for construction of the core protein-protein interaction(PPI)network and GO and KEGG enrichment analyses.Forty male C57 mice were randomized into normal control group,model group,mesalazine group and Cynanchum wilfordii group(n=10),and in the latter 3 groups,mouse UC models were established by treatment with 2.5%DSS and the latter 2 groups drug interventions by gavage.The therapeutic effect was evaluated by recording body weight changes and DAI score.Pathological changes of the colon tissue were observed with HE and AB-PAS staining,and JAK2 and STAT3 protein expressions were detected with Western blotting.The metabolites and metabolic pathways were identified by metabonomics analysis.Results We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts,including 19 steroids.A total of 177 Cynanchum wilfordii targets,5406 UC genes,and 117 intersection genes were obtained.JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways.Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice(P<0.05),alleviated intestinal pathologies,and decreased JAK2 and STAT3 protein expressions in the colon tissues.Most of the 83 intersecting differential metabolites between the control,model and Cynanchum wilfordii groups were identified as glycerophospholipids,arachidonic acid,and amino acids involving glycerophospholipid metabolism and other pathways.Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites.Conclusion Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.关键词
隔山消/溃疡性结肠炎/代谢组学/UPLC-QE-MS/甾体类Key words
Cynanchum wilfordii(Maxim.)Hook.F/ulcerative colitis/metabolomics/UPLC-QE-MS/steroids引用本文复制引用
于官正,程炜强,涂星,张满,李鸿,聂娟..隔山消治疗溃疡性结肠炎的机制:基于UPLC-QE-MS、网络药理学及代谢组学技术[J].南方医科大学学报,2024,44(8):1485-1496,12.基金项目
国家自然科学基金青年科学基金(82304829) （82304829）
恩施州科技项目技术支撑类重点项目(D20220065)Supported by Natural Science Foundation for the Youth(NSFY)of China(82304829). （D20220065）
