中国临床药理学杂志2025，Vol.41Issue(17)：2496-2502,7.DOI:10.13699/j.cnki.1001-6821.2025.17.017
靶向代谢组学整合网络药理学研究栀子的"自解毒"效应及机制
Research of targeted metabolomics integrated network pharmacology on the"self-detoxification"effect and mechanism of Gardenia jasminoides Ellis
摘要
Abstract
Objective To investigate the effect of Gardenia jasminoides Ellis(Zhi-zi)in alleviating the hepatotoxicity induced by its constituent,genipin,which is called the"self-detoxification"effect,and to explore its mechanism through targeted metabolomics and integrated network pharmacology.Methods Male mice of the Kunming breed were randomly divided into three groups(n=8)including blank group,control group and experimental group.Blank group was administered a blank solvent 0.5％carboxymethyl cellulose(CMC-Na)by gavage;control group was administered genipin by gavage at a dose of 100 mg·kg-1·d-1,and experimental group was administered 100 mg·kg-1·d-1 genipin and 520 mg·kg-1·d-1 Zhi-zi aqueous extract powder by gavage.After 28 days of continuous administration,serum biochemical indicators were measured using an automated biochemical analyzer,liver tissue pathology was examined using hematoxylin and eosin(HE)staining,and differential metabolites were quantified and analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)for targeted metabolomics analysis.The targets associated with active compounds in Zhi-zi,genipin,and liver damage were predicted separately.Finally,the results of metabolomics and network pharmacology were integrated to screen the potential targets related to the self-detoxification effect of Zhi-zi.Results The alanine transaminase(ALT)levels in experimental group,control group and blank group were(35.75±8.50),(53.00±14.43)and(37.38±3.11)U·L-1,respectively;the aspartate transaminase(AST)levels were(123.38±31.40),(146.50±19.73)and(115.75±17.44)U·L-1,respectively.Compared with control group,experimental group showed significant decrease in ALT levels,with statistically significant difference(P＜0.05).Compared with control group,the AST levels in experimental group showed no statistically significant difference(P＞0.05).Targeted metabolomics identified 8 characteristic endogenous metabolites including fumaric acid,isocitric acid,maleic acid,ornithine,aminocaproic acid,isoLCA,pipecolic acid and pyrrole-2-carboxylic acid,and the metabolic pathways induced by these 8 differentially expressed metabolites were primarily associated with arginine biosynthesis and the tricarboxylic acidcycle(TCA)metabolic pathways.Conclusion Zhi-zi can improve the metabolic disorders of endogenous metabolites in the liver caused by genipin by affecting the arginine biosynthesis and the TCA metabolic pathway,and improve inflammation and oxidative stress by acting on the corresponding targets to alleviate the hepatic injuries caused by genipin and exerting the self-detoxification effect.关键词
栀子/京尼平/自解毒/肝毒性/靶向代谢组学Key words
Gardenia jasminoides Ellis/genipin/self-detoxification/hepatotoxicity/targeted metabolomics分类
中医学引用本文复制引用
吕东霞,张帆,高昕,张航星,王国旭,饶志,魏玉辉..靶向代谢组学整合网络药理学研究栀子的"自解毒"效应及机制[J].中国临床药理学杂志,2025,41(17):2496-2502,7.基金项目
国家自然科学基金资助项目(82174067) （82174067）
兰州大学2024年大学生创新创业推荐基金资助项目(202210730179) （202210730179）
