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基于 UPLC-Q-TOF/MS 的阿司匹林丁香酚酯对动脉粥样硬化模型大鼠代谢组学干预作用研究。

UPLC-Q-TOF/MS-based metabonomic studies on the intervention effects of aspirin eugenol ester in atherosclerosis hamsters.

机构信息

Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Science of Chinese Academy of Agricultural Sciences, Lanzhou, China.

出版信息

Sci Rep. 2017 Sep 5;7(1):10544. doi: 10.1038/s41598-017-11422-7.

Abstract

Based on the pro-drug principle, aspirin and eugenol were used to synthesize aspirin eugenol ester (AEE) by esterification reaction. In present study, the anti-atherosclerosis effects of AEE were investigated in hamsters with the utilization of metabonomic approach based on UPLC-Q-TOF/MS. Biochemical parameters and histopathological injures in stomach, liver and aorta were evaluated. In atherosclerotic hamster, oral administration of AEE normalized biochemical profile such as reducing TG, TCH and LDL, and significantly reduced body weight gain, alleviated hepatic steatosis and improved pathological lesions in aorta. Slight damages in stomach mucous were found in AEE group. Plasma and urine samples in control, model and AEE groups were scattered in the partial least squares-discriminate analysis (PLS-DA) score plots. Thirteen endogenous metabolites in plasma such as lysophosphatidylcholine (LysoPC), leucine and valine, and seventeen endogenous metabolites in urine such as citric acid, phenol sulphate and phenylacetylglycine were selected as potential biomarkers associated with atherosclerosis. They were considered to be in response to anti-atherosclerosis effects of AEE, mainly involved in glycerophospholipid metabolism, amino acid metabolism and energy metabolism. This study extended the understanding of endogenous alterations of atherosclerosis and offered insights into the pharmacodynamic activity of AEE.

摘要

基于前药原理,采用酯化反应将阿司匹林和丁香酚合成阿司匹林丁香酚酯(AEE)。本研究采用基于 UPLC-Q-TOF/MS 的代谢组学方法研究 AEE 的抗动脉粥样硬化作用。评估了胃、肝和主动脉的生化参数和组织病理学损伤。在动脉粥样硬化的仓鼠中,AEE 的口服给药使生化特征正常化,如降低 TG、TCH 和 LDL,并显著减轻体重增加、缓解肝脂肪变性和改善主动脉的病理损伤。在 AEE 组中发现胃黏膜有轻微损伤。对照、模型和 AEE 组的血浆和尿液样本在偏最小二乘判别分析(PLS-DA)得分图中分散。血浆中 13 种内源性代谢物,如溶血磷脂酰胆碱(LysoPC)、亮氨酸和缬氨酸,以及尿液中 17 种内源性代谢物,如柠檬酸、苯酚硫酸盐和苯乙酰甘氨酸被选为与动脉粥样硬化相关的潜在生物标志物。它们被认为是对 AEE 的抗动脉粥样硬化作用的反应,主要涉及甘油磷脂代谢、氨基酸代谢和能量代谢。这项研究扩展了对动脉粥样硬化内源性变化的理解,并深入了解了 AEE 的药效活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f137/5585262/0e6790af2533/41598_2017_11422_Fig1_HTML.jpg

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