海南医科大学学报2025,Vol.31Issue(8):617-627,11.DOI:10.13210/j.cnki.jhmu.20241101.003
基于代谢组学和网络药理学探讨二至丸治疗LPS诱导小鼠肝炎的药效物质及机制研究
Active components and mechanism of Erzhi pills in treating LPS-induced hepatitis in mice based on metabolomics and network pharmacology
摘要
Abstract
Objective:To explore the active components basis and mechanism of Erzhi pills in treating hepatitis.Method:39 C57BL/6J mice were randomly divided into blank group(Control),model group(LPS)and Erzhi pills group(EZP).Lipopoly-saccharide(LPS)was injected intraperitoneal to replicate the hepatitis mouse model.The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum of mice were measured by automatic biochemical instrument.The expres-sion levels of tumor necrosis factor α(TNF-α)and interleukin-1β(IL-1β)in mouse liver were determined by enzyme-linked immu-nosorbent assay(ELISA).The liver morphology was observed by HE staining.UPLC-Q-TOF-MS/MS was used to detect the hepatic components of Erzhi pills.Metabolomics was used to detect different metabolites in liver tissue of mice in each group.Net-work pharmacology predicted the potential target and pathway of the hepatic components of Erzhi pills.Result:Compared with the Control group,ALT and AST levels in the serum,TNF-α and IL-1β levels in liver tissue were increased significantly in LPS group,the structure of liver lobules was abnormal,and a large number of inflammatory cells were infiltrated.After the intervention of Erzhi pills in LPS group,the above indexes could be reversed effectively.A total of 24 components such as luteolin,apigenin and ferulic acid were identified by LC-MS.31 different metabolites of ADP,glutamic acid and glutathione were identified by liver metabolomics,and 6 metabolic pathways were mainly concentrated in phenylalanine,tyrosine and tryptophan biosynthesis,phe-nylalanine metabolism and glutathione metabolism.Network pharmacology predicted 303 intersection targets of Erzhi pills and hep-atitis,and 22 core targets were identified by PPI network screening,involving HIF-1,PI3K-AKT,MAPK and other signaling pathways.Conclusion:This study preliminarily revealed the pharmacodynamic material basis of Erzhi pills and its mechanism of improving LPS-induced hepatitis in mice,which provided a basis for further research.关键词
二至丸/肝炎/UPLC-Q-TOF-MS/MS/药效物质/网络药理学/非靶向代谢组学Key words
Erzhi pills/Hepatitis/UPLC-Q-TOF-MS/MS/Active components/Network pharmacology/Non-targeted metabolomics分类
医药卫生引用本文复制引用
李雪,薛傲,李光,杨萌,赵红梅,赵灿,任毅帆,张亚峰,张宁..基于代谢组学和网络药理学探讨二至丸治疗LPS诱导小鼠肝炎的药效物质及机制研究[J].海南医科大学学报,2025,31(8):617-627,11.基金项目
General Project of National Natural Science Foundation of China(82174007) (82174007)
Central Support for Local University Reform and Development Fund Talent Training Project(Research on the Mechanism of Erzhi Pill in Preventing and Treating AD) (Research on the Mechanism of Erzhi Pill in Preventing and Treating AD)
Jiangsu Province Traditional Chinese Medicine Degenerative Osteoarthritis Clinical Medical Innovation Center Funding Project(20210405) 国家自然科学基金面上项目(82174007) (20210405)
中央支持地方高校改革发展资金人才培养项目(二至丸防治AD作用机理研究) (二至丸防治AD作用机理研究)
江苏省中医退行性骨关节病临床医学创新中心资助项目(20210405) (20210405)