Evaluation on antithrombotic effect of aspirin eugenol ester from the view of platelet aggregation, hemorheology, TXB2/6-keto-PGF1α and blood biochemistry in rat model

Ma, Ning; Liu, Xi Wang; Yang, Ya; Shen, Dong Shuai; Zhao, Xiao Le; Mohamed, Isam; Kong, Xiao Jun; Li, Jian Yong

doi:10.1186/s12917-016-0738-0

Cited by 27 publications

(18 citation statements)

References 41 publications

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“…As a promising drug candidate, AEE reduce the side effects of aspirin and eugenol, and can generate synergistic effects to improve therapeutic effects. Results of pharmacodynamics experiments revealed that AEE carried many biological activities, including anti-inflammation, anti-thrombosis, anti-oxidation, analgesia and antipyresis [ 5 , 15 , 16 ]. In our previous study, AEE treatment could regulate the disorders of serum lipid in hyperlipidemic rat model fed with HFD [ 10 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

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

Liu

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.

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Section: Discussionmentioning

confidence: 99%

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

Liu

Kong

et al. 2017

Lipids Health Dis

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“…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

Liu

et al. 2019

British J Pharmacology

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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.

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“…Therefore, AEE could improve structural stability and reduce gastrointestinal side effects [14]. Currently, the teratogenicity, metabolism, acute and sub chronic toxicity and pharmacodynamics of AEE have been estimated, and the relative results indicate that AEE is a safe and promising drug candidate [14,15,16,17,18].…”

Section: Introductionmentioning

confidence: 99%

UPLC-Q-TOF/MS-Based Plasma Metabolomics to Evaluate the Effects of Aspirin Eugenol Ester on Blood Stasis in Rats

Shen

Yang

et al. 2019

Molecules

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Aspirin eugenol ester (AEE) is a novel compound that is formed from the esterification of aspirin (acetylsalicylic acid (ASA)) and eugenol. This study aimed to investigate the effects of AEE on blood stasis in rats and to characterize the underlying mechanisms using a plasma metabolomic study. The results indicate that AEE and ASA could modulate whole blood viscosity (WBV), plasma viscosity (PV), blood coagulation parameters, platelet count, platelet aggregation, lactate dehydrogenase (LDH), creatinine (CR) and the levels of thromboxane A2 (TXA2) and 6-keto prostaglandin F1α (6-keto-PGF1α). The metabolic profiles of the plasma samples from all groups were clearly separated in the score plots. Nineteen potential metabolites were selected and identified, and disordered levels of these metabolites could be regulated by AEE and ASA. Pathway analysis showed that the mechanism of action of AEE on blood stasis might be principally related to the metabolism of amino acid, fatty acid, energy and glycerophospholipid. The above results indicate that AEE protected the rats against blood stasis, and that this effect might have been caused by the anticoagulation activity of AEE and its abilities to maintain a balance between TXA2 and PGI2, reduce blood viscosity, inhibit platelet aggregation and normalize the plasma metabolic profile.

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Evaluation on antithrombotic effect of aspirin eugenol ester from the view of platelet aggregation, hemorheology, TXB2/6-keto-PGF1α and blood biochemistry in rat model

Cited by 27 publications

References 41 publications

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

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

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

UPLC-Q-TOF/MS-Based Plasma Metabolomics to Evaluate the Effects of Aspirin Eugenol Ester on Blood Stasis in Rats

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