Lowering effects of aspirin eugenol ester on blood lipids in rats with high fat diet

Kong

et al. 2017

Lipids Health Dis

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BackgroundBased on the pro-drug principle, aspirin and eugenol were esterified to synthesize aspirin eugenol ester (AEE). The anti-hyperlipidemia effect of aspirin eugenol ester has been confirmed in hyperlipidemic rat induced by high fat diet (HFD). However, its effect on liver and feces metabonomic profiles remains unknown.MethodsSuspension of AEE was prepared in 5% carboxymethyl cellulose sodium (CMC-Na). Thirty rats were divided into control, model and AEE groups. The control and model rats were fed with normal diet or HFD for 13 weeks, respectively. Rats in AEE-treated group were fed with HFD for 8 weeks to induce hyperlipidemia, and then given AEE once daily by oral gavage for 5 weeks at the dosage of 54 mg/kg body weight. After drug intervention, lipid profile analysis and oil red O staining were carried out to confirm the lipid accumulation in liver tissue. UPLC-Q-TOF/MS-based liver and feces metabonomics coupled with pathway analysis were conducted to evaluate the changes of metabolic profile and endogenous metabolites.ResultsIn liver tissue, oral administration of AEE significantly reduced lipid droplets and the levels of triglyceride (TG) and low-density lipoprotein (LDL). Using principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA), distinct changes in metabolite patterns in feces and liver were observed. Liver and feces samples in control, model and AEE groups were scattered in PLS-DA score plots. 28 metabolites in liver and 22 in feces were identified as potential biomarkers related to hyperlipidemia. As possible drug targets, the perturbations of those biomarkers can be regulated by administration of AEE.ConclusionAnti-hyperlipidemia effect of AEE was confirmed by lipid analysis, oil red O staining and metabolomics analysis. The mechanism of AEE might be associated with the changes in the metabolism of glycerophospholipid, amino acid, fatty acid, sphingolipid, purine, bile acid and glutathione.Electronic supplementary materialThe online version of this article (10.1186/s12944-017-0633-0) contains supplementary material, which is available to authorized users.

Section: Discussionmentioning

confidence: 99%

Feces and liver tissue metabonomics studies on the regulatory effect of aspirin eugenol eater in hyperlipidemic rats

Kong

et al. 2017

Lipids Health Dis

Self Cite

“…Aspirin eugenol ester (AEE) is synthesized by combining aspirin with eugenol based on the prodrug principal (Li et al, ). Pharmacological and pharmacodynamic studies showed that AEE has significantly reduced side effects and enhanced pharmacological activity as an anti‐thrombus, anti‐atherosclerosis, and anti‐oxidant, compared with either aspirin or eugenol alone (Karam et al, ; Karam et al, ; Li et al, ; Ma et al, ; Ma et al, ; Ma, Yang, Liu, Yang, et al, ; Ye et al, ). However, the molecular mechanisms through which AEE inhibits atherosclerosis, thrombus, and oxidative stress are unclear.…”

Section: Introductionmentioning

confidence: 99%

Aspirin eugenol ester attenuates oxidative injury of vascular endothelial cells by regulating NOS and Nrf2 signalling pathways

Huang

Yang

et al. 2019

British J Pharmacology

Background and Purpose: Aspirin eugenol ester (AEE) is a new drug compound synthesized by combining aspirin with eugenol. It was reported to possess antithrombotic, anti-atherosclerotic, and anti-oxidative effects. However, its molecular mechanism against oxidative injury is unclear. This study investigated how AEE affected the oxidative injury of vascular endothelial cells in vivo and in vitro. Experimental Approach: A hamster model of atherosclerosis induced by a high fat diet (HFD) and an in vitro model of oxidative stress, H 2 O 2 -induced apoptosis of HUVECs, were used to investigate the anti-oxidative effects of AEE. Key Results: AEE significantly reduced the stimulatory effect of HFD on malondialdehyde, the inhibitory effect of HFD on SOD activity and GSH/GSSG ratio, and the overexpression of inducible NOS (iNOS) in the aorta. In vitro, incubation of HUVECs with H 2 O 2 led their apoptosis, dysfunctions of the NO systems (including increased iNOS activity, decreased endothelial NOS activity, and increased production of NO), an imbalance in calcium homeostasis and energy metabolism with an increase in intracellular free calcium and decrease in ATP, and a down-regulation of Nrf2. In contrast, in the HUVECs pretreated with 1 μM AEE for 24 hr, the above adverse effects induced by H 2 O 2 were significantly ameliorated. Moreover, the decrease in NO production and activity of iNOS induced by AEE was significantly attenuated in Nrf2-inhibited HUVECs.Conclusion and Implication: AEE protects vascular endothelial cells from oxidative injury by regulating NOS and Nrf2 signalling pathways. This suggests that AEE is a novel potential agent for the prevention of atherosclerosis.

“…We previously established the hyperlipidemia model in rats induced by HFD, and investigated the regulation effects of AEE on blood lipids [16, 17]. Moreover, the effects of AEE on the metabonomics profiles of plasma, urine, liver and feces were also explored [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Aspirin eugenol ester regulates cecal contents metabolomic profile and microbiota in an animal model of hyperlipidemia

Kong

et al. 2018

BMC Vet Res

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BackgroundHyperlipidemia, with an increasing of prevalence, has become one of the common metabolic diseases in companion animal clinic. Aspirin eugenol ester (AEE) is a novel compound that exhibits efficacious anti-hyperlipidemia activities. However, its mechanisms are still not completely known. The objective of present study was to investigate the intervention effects of AEE on cecal contents metabonomics profile and microbiota in hyperlipidemia rats.ResultsThree groups of rats were fed with a control diet, or high fat diet (HFD) containing or not AEE. The results showed the beneficial effects of AEE in HFD-fed rats such as the reducing of aspartate aminotransferase (AST) and total cholesterol (TCH). Distinct changes in metabonomics profile of cecal contents were observed among control, model and AEE groups. HFD-induced alterations of eight metabolites in cecal contents mainly related with purine metabolism, linoleic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and pyrimidine metabolism were reversed by AEE treatment. Principal coordinate analysis (PCoA) and cluster analysis of microbiota showed altered patterns with distinct differences in AEE group versus model group, indicating that AEE treatment improved the negative effects caused by HFD on cecal microbiota. In addition, the correction analysis revealed the possible link between the identified metabolites and cecal microbiota.ConclusionsThis study showed regulation effects of AEE on cecal contents metabonomics profile and microbiota, which could provide information to reveal the possible underlying mechanism of AEE on hyperlipidemia treatment.Electronic supplementary materialThe online version of this article (10.1186/s12917-018-1711-x) contains supplementary material, which is available to authorized users.