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

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 ac...

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Autores principales:	Lu Xiao-Rong, Ma Ning, Liu Xi-Wang, Li Shi-Hong, Qin Zhe, Bai Li-Xia, Yang Ya-Jun, Li Jian-Yong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	aspirin eugenol ester hyperlipidemia metabolomics bile acids cholesterol Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4652ceaa0694413b81991a410eb6af3a
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spelling	oai:doaj.org-article:4652ceaa0694413b81991a410eb6af3a2021-12-01T01:35:28ZUntargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A11663-981210.3389/fphar.2021.733789https://doaj.org/article/4652ceaa0694413b81991a410eb6af3a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.733789/fullhttps://doaj.org/toc/1663-9812Hyperlipidemia 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 7α-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.Lu Xiao-RongMa NingMa NingLiu Xi-WangLi Shi-HongQin ZheBai Li-XiaYang Ya-JunLi Jian-YongFrontiers Media S.A.articleaspirin eugenol esterhyperlipidemiametabolomicsbile acidscholesterolTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aspirin eugenol ester hyperlipidemia metabolomics bile acids cholesterol Therapeutics. Pharmacology RM1-950
spellingShingle	aspirin eugenol ester hyperlipidemia metabolomics bile acids cholesterol Therapeutics. Pharmacology RM1-950 Lu Xiao-Rong Ma Ning Ma Ning Liu Xi-Wang Li Shi-Hong Qin Zhe Bai Li-Xia Yang Ya-Jun Li Jian-Yong Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1
description	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 7α-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.
format	article
author	Lu Xiao-Rong Ma Ning Ma Ning Liu Xi-Wang Li Shi-Hong Qin Zhe Bai Li-Xia Yang Ya-Jun Li Jian-Yong
author_facet	Lu Xiao-Rong Ma Ning Ma Ning Liu Xi-Wang Li Shi-Hong Qin Zhe Bai Li-Xia Yang Ya-Jun Li Jian-Yong
author_sort	Lu Xiao-Rong
title	Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1
title_short	Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1
title_full	Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1
title_fullStr	Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1
title_full_unstemmed	Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1
title_sort	untargeted and targeted metabolomics reveal the underlying mechanism of aspirin eugenol ester ameliorating rat hyperlipidemia via inhibiting fxr to induce cyp7a1
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4652ceaa0694413b81991a410eb6af3a
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Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1

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