代谢组学探讨布渣叶干预高脂血症小鼠降脂作用及精氨酸-脯氨酸-多胺代谢轴调控机制OA
Metabolomics Reveals Lipid-lowering Effects of Microctis Folium in Hyperlipidemic Mice via Modulation of the Arginine-Proline-Polyamine Axis
以高脂饮食诱导的高脂血症小鼠为模型,系统评价布渣叶(Microctis Folium)的降脂与护肝作用,并结合非靶向与靶向代谢组学阐明其对精氨酸-脯氨酸-多胺代谢轴的调控机制.采用超高效液相色谱-四极杆-飞行时间质谱开展血清非靶向代谢组学,筛选差异代谢物并进行通路富集;基于超高效液相色谱-三重四极杆串联质谱靶向代谢组学定量L-精氨酸、脯氨酸、肌酸及多胺(亚精胺、精胺)等关键代谢物.结果显示,布渣叶各剂量组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)显著降低并下调丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST),提升高密度脂蛋白胆固醇(HDL-C).非靶向结果提示高脂饮食致多通路紊乱,其中精氨酸-脯氨酸代谢富集显著;差异代谢物主要涉及氨基酸及衍生物、多胺、肌酸相关物质,伴随脂类与有机酸异常,布渣叶可整体逆转相关代谢失衡.靶向验证表明,模型组L-精氨酸、脯氨酸、肌酸、精胺、亚精胺水平下降,布渣叶可显著促其回升并趋近对照组.综上,布渣叶具有明确的降脂护肝活性,其机制可能通过调节精氨酸-脯氨酸-多胺代谢轴,改善氮代谢与能量代谢重构,促进代谢稳态恢复.研究结果可为布渣叶活性成分筛选与开发提供依据.
This study employed a high-fat diet(HFD)-induced hyperlipidemia mice model to system‑atically evaluate the lipid-lowering and hepatoprotective effects of Microctis Folium and to elucidate its regulatory mechanism on the arginine-proline-polyamine metabolic axis using integrated untarget‑ed and targeted metabolomics.Serum untargeted metabolomics was performed using UPLC-QTOF-MS/MS to screen for differential metabolites and conduct pathway enrichment analysis.Subsequently,targeted metabolomics based on UPLC-TQ-MS/MS was employed to quantify key metabolites includ‑ing L-arginine,proline,creatine,and polyamines(spermidine and spermine).Microctis Folium significantly reduced TC,TG,and LDL-C levels and decreased ALT and AST while increasing HDL-C across dose groups.Untargeted metabolomics revealed broad metabolic disturbances induced by HFD,with significant enrichment of arginine and proline metabolism;differential metabolites mainly involved amino acids and derivatives,polyamines,creatine-related metabolites,as well as lipids and organic acids.Microctis Folium treatment globally reversed these metabolic abnormalities.Targeted quantification further confirmed that L-arginine,proline,creatine,and polyamines(spermine/spermidine)were decreased in the model group,and Microctis Folium markedly restored their levels toward those of controls.Collectively,Microctis Folium exhibits pronounced lipid-lower‑ing and hepatoprotective activities,which may be mediated by modulation of the arginine-proline-polyamine metabolic axis and associated metabolic remodeling of nitrogen and energy metabolism,thereby promoting restoration of metabolic homeostasis.These findings provide metabolomics-based evidence for the mechanism of action of Microctis Folium and support future screening of its bioactive constituents and translational development.
肖观林;陈婉纯;刘焰嫦;欧阳云徽;张靖年;陈伟韬;毕晓黎
广东省中医药工程技术研究院,广东省中医药研究开发重点实验室,广东 广州 510095广州中医药大学第五临床医学院,广东 广州 510405广州中医药大学第五临床医学院,广东 广州 510405广州中医药大学第五临床医学院,广东 广州 510405广东省中医药工程技术研究院,广东省中医药研究开发重点实验室,广东 广州 510095广东省中医药工程技术研究院,广东省中医药研究开发重点实验室,广东 广州 510095广东省中医药工程技术研究院,广东省中医药研究开发重点实验室,广东 广州 510095
化学化工
布渣叶高脂血症精氨酸-脯氨酸-多胺代谢超高效液相色谱-四极杆-飞行时间质谱超高效液相色谱-三重四极杆串联质谱
Microcos Foliumhyperlipidemiaarginine-proline-polyamine metabolismUPLC-QTOF-MS/MSUPLC-TQ-MS/MS
《分析测试学报》 2026 (5)
930-939,10
广东省基础与应用基础研究基金项目(2024A1515012809)广州地区中医药重大科技项目(2025QN003)广东省中医药局科研项目(20251034)广州中医药大学校院联合科技创新基金(GZYSE2024G07)2025年度国家中医药管理局-广东省国家中医药综合改革示范区科技共建项目(GZY-KJS-GD-2025-017)
评论