基于空间代谢组学方法研究人参治疗阿尔兹海默症大鼠的药效物质及作用机制  

Spatial Metabolomics Approach Reveals the Pharmacodynamic Substances and Mechanism of Panax ginseng in Alzheimer’s Disease Mice

作　　者：范宇婷 刘志强[1,2] 邢俊鹏[1] 郑重[1] 宋凤瑞[1,2] 刘舒[1,2] FAN Yu-ting;LIU Zhi-qiang;XING Jun-peng;ZHENG Zhong;SONG Feng-rui;LIU Shu(National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026,China)

机构地区：[1]中国科学院长春应用化学研究所,长春质谱中心&吉林省中药化学与质谱重点实验室,吉林长春130022 [2]中国科学技术大学应用化学与工程学院,安徽合肥230026

出　　处：《质谱学报》2024年第6期723-738,I0001,共17页Journal of Chinese Mass Spectrometry Society

基　　金：国家自然科学基金面上项目(81873193,U19A2012)。

摘　　要：本文采用基于空气动力辅助解吸电喷雾离子化质谱成像(AFADESI-MSI)技术的空间代谢组学方法,全面探讨了人参在分子水平上治疗阿尔兹海默症(AD)的药效物质基础及作用机制。药效学结果表明,人参提取物可显著改善AD模型大鼠的脑病理损伤状态,提高空间学习记忆能力;代谢组学结果表明,人参显著回调了与AD密切相关的19种生物标志物水平,涉及精氨酸和脯氨酸代谢、嘌呤代谢、三羧酸(TCA)循环和脂肪酸代谢等8条代谢通路。最后,在脑组织中检测出7种人参活性成分,这些物质可能通过调节与神经炎症、神经元损伤、能量缺失以及脂肪酸异常代谢密切相关的代谢途径上游靶点发挥作用,实现对关键代谢物水平的精确调控,从而达到治疗AD的目的。利用质谱成像可以将内外源性物质的空间分布进行对应分析,更清晰地阐释药物成分的具体作用机制。Panax ginseng,a venerable herb in traditional Chinese medicine,boasts a rich history of usage in the treatment of dementia,particularly in its various manifestations.However,despite its long-standing popularity and empirical evidence of effectiveness,the precise mechanisms underlying its therapeutic actions have remained elusive.Currently,research on pharmacodynamic components and mechanisms predominantly utilizes serum pharmacology and metabolomics research methods that are based on liquid chromatography-mass spectrometry technology.However,these methods are unable to capture the spatial distribution information of relevant substances,leading to a lack of comprehensive understanding of the pharmacodynamic components and their underlying mechanisms.To bridge this gap in knowledge,a method of spatial metabolomics and air flow assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI),was used to delve into the molecular mechanisms of Panax ginseng in treating Alzheimer’s disease(AD).The pharmacodynamic results demonstrated that Panax ginseng extract can significantly improve the state of brain pathological damage and spatial learning memory ability in AD model rats.This finding highlights the potential of ginseng as a therapeutic agent in AD management.Furthermore,the metabolomics analysis revealed that Panax ginseng modulates the levels of 19 biomarkers that are intricately linked to AD.These biomarkers span across 8 key metabolic pathways,including arginine and proline metabolism,purine metabolism,the tricarboxylic acid(TCA)cycle,and fatty acid metabolism.These pathways are essential for maintaining neuronal health and function,and their dysregulation is often associated with the pathogenesis of AD.Importantly,the study identified 7 active ginseng constituents that accumulate in brain tissue.These compounds work in a holistic manner to treat AD by modulating metabolites related to neuroinflammation,neuronal damage,energy deficits,and abnormal fatty acid metabolism.The comprehensive appr

关 键 词：空间代谢组学 质谱成像 人参 阿尔兹海默症(AD) 

分 类 号：O657.63[理学—分析化学]