Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1

文献类型： 外文期刊

第一作者： Lu, Xiao-Rong

作者： Lu, Xiao-Rong;Ma, Ning;Liu, Xi-Wang;Li, Shi-Hong;Qin, Zhe;Bai, Li-Xia;Yang, Ya-Jun;Li, Jian-Yong;Ma, Ning

作者机构：

关键词： aspirin eugenol ester; hyperlipidemia; metabolomics; bile acids; cholesterol

期刊名称：FRONTIERS IN PHARMACOLOGY （ 影响因子：5.988； 五年影响因子：6.455 ）

ISSN：

年卷期： 2021 年 12 卷

页码：

收录情况： SCI

摘要： Hyperlipidemia is an important lipid disorder and a risk factor for health. Aspirin eugenol ester (AEE) is a novel synthetic compound which is made up of two chemical structural units from aspirin and eugenol. Therapeutic effect of AEE on hyperlipidemia has been confirmed in animal model. But the action mechanism of AEE on hyperlipidemia is still poorly understood. In this study, we investigated the effects of AEE on liver and feces metabolic profile through UPLC-Q-TOF/MS-based untargeted metabolomics in hyperlipidemia hamster induced with high fat diet (HFD), and the effects of AEE on the expression of genes and proteins related to cholesterol and bile acid (BA) in HFD-induced hyperlipidemia SD rat. The concentrations of 26 bile acids (BAs) in the liver from hyperlipidemia SD rat were also quantified with the application of BA targeted metabolomics. The results of untargeted metabolomics showed that the underlying mechanism of AEE on hyperlipidemia was mainly associated with amino acid metabolism, glutathione metabolism, energy metabolism, BA metabolism, and glycerophospholipid metabolism. AEE induced the expression of the BA-synthetic enzymes cholesterol 7 alpha-hydroxylase (CYP7A1) by the inhibition of BA nuclear receptor farnesoid X receptor (FXR) in liver, which resulted in accelerating the conversion of cholesterol into bile acids and excrete in feces. The results of BA targeted metabolomics showed that AEE elevated the glycine-conjugated BA level and decreased the tauro-conjugated BA level. In conclusion, this study found that AEE decreased FXR and increased CYP7A1 in the liver, which might be the possible molecular mechanisms and targets of AEE for anti-hyperlipidemia therapies.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序