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代谢组学方法评估冷应激大鼠体内人参皂苷的代谢变化及内外源性代谢相互作用

Metabonomics Approach to Assessing the Metabolism Variation and Endoexogenous Metabolic Interaction of Ginsenosides in Cold Stress Rats.

作者信息

Zhang Zhihao, Wang Xiaoyan, Wang Jingcheng, Jia Zhiying, Liu Yumin, Xie Xie, Wang Chongchong, Jia Wei

机构信息

Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine and ‡Instrumental Analysis Center of SJTU, Shanghai Jiao Tong University , Shanghai, 200240, P. R. China.

出版信息

J Proteome Res. 2016 Jun 3;15(6):1842-52. doi: 10.1021/acs.jproteome.6b00015. Epub 2016 May 13.

DOI:10.1021/acs.jproteome.6b00015
PMID:27150950
Abstract

Metabolic profiling technology, a massive information provider, has promoted the understanding of the metabolism of multicomponent medicines and its interactions with endogenous metabolites, which was previously a challenge in clarification. In this study, an untargeted GC/MS-based approach was employed to investigate the urinary metabolite profile in rats with oral administration of ginsenosides and the control group. Significant changes of urinary metabolites contents were observed in the total ginsenosides group, revealing the impact of ginsenosides as indicated by the up- or down-regulation of several pathways involving neurotransmitter-related metabolites, tricarboxylic acid (TCA) cycle, fatty acids β-oxidation, and intestinal microflora metabolites. Meanwhile, a targeted UPLC-QQQ/MS-based metabonomic approach was developed to investigate the changes of urinary ginsenoside metabolites during the process of acute cold stress. Metabolic analysis indicated that upstream ginsenosides (rg1, re, and rf) increased significantly, whereas downstream ginsenosides (ck, ppd, and ppt) decreased correspondingly after cold exposure. Finally, the relationships between ginsenosides and significantly changed metabolites were investigated by correlation analysis.

摘要

代谢谱分析技术作为大量信息的提供者,促进了对多组分药物代谢及其与内源性代谢物相互作用的理解,而这在以前是难以阐明的挑战。在本研究中,采用基于非靶向气相色谱/质谱联用的方法来研究口服人参皂苷的大鼠和对照组的尿液代谢物谱。在总人参皂苷组中观察到尿液代谢物含量的显著变化,揭示了人参皂苷的影响,表现为涉及神经递质相关代谢物、三羧酸(TCA)循环、脂肪酸β-氧化和肠道微生物群代谢物的几条途径的上调或下调。同时,开发了一种基于靶向超高效液相色谱-串联四极杆质谱联用的代谢组学方法来研究急性冷应激过程中尿液人参皂苷代谢物的变化。代谢分析表明,冷暴露后上游人参皂苷(rg1、re和rf)显著增加,而下游人参皂苷(ck、ppd和ppt)相应减少。最后,通过相关性分析研究了人参皂苷与显著变化的代谢物之间的关系。

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