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

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.

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

“…The HFD‐fed hamster is thought to be a convenient and sensitive model for rapid establishment of atherosclerosis (Singhal, Finver‐Sadowsky, McSherry, & Mosbach, ; Zhao, Chen, Mao, Min, & Cao, ). It had been confirmed that AEE can prevent the severe atherosclerotic lesions in the aorta of HFD‐fed Syrian golden (Ma, Yang, Liu, Kong, et al, ), while the mechanism by which AEE protects against the injury of aorta induced by HFD is still unknown. The metabolomic analysis of HFD‐fed hamsters and AEE‐treated HFD‐fed hamsters suggested that protective effect of AEE against the injury of aorta might be related to a reduction in oxidative stress (Ma, Yang, Liu, Kong, et al, ).…”

“…It had been confirmed that AEE can prevent the severe atherosclerotic lesions in the aorta of HFD‐fed Syrian golden (Ma, Yang, Liu, Kong, et al, ), while the mechanism by which AEE protects against the injury of aorta induced by HFD is still unknown. The metabolomic analysis of HFD‐fed hamsters and AEE‐treated HFD‐fed hamsters suggested that protective effect of AEE against the injury of aorta might be related to a reduction in oxidative stress (Ma, Yang, Liu, Kong, et al, ). In the present study, the oxidative balance was disturbed in plasma of HFD‐fed atherosclerotic hamsters, and AEE treatment significantly attenuated the oxidative imbalance caused by HFD ( P < 0.05).…”

“…The atherosclerosis model of Syrian golden hamsters was developed, and the treatments were prepared following the methods described in our previous studies (Ma, Yang, Liu, Kong, et al, ). In brief, All hamsters were housed in facilities by group at a controlled relative humidity (45–65%),12 h light/12 h dark cycle and temperature (22 ± 2°C).…”

“…However, the molecular mechanisms through which AEE inhibits atherosclerosis, thrombus, and oxidative stress are unclear. A metabolomic analysis in high fat diet (HFD)‐induced atherosclerotic hamsters and AEE‐treated hamsters suggested that AEE protects the aorta from injury, and this suggests it has an effect on oxidative stress (Ma, Yang, Liu, Kong, et al, ). Oxidative stress is a well‐known cause of cardiovascular diseases.…”

Antihypertensive activity of oleanolic acid is mediated via downregulation of secretory phospholipase A2 and fatty acid synthase in spontaneously hypertensive rats

“…At 12 h after the last treatment, the rats were anesthetized with sodium pentobarbital (40 mg/kg, intraperitoneal) ( 73 ) and blood samples were collected into normal vacuum tubes via cardiac puncture. The serum was collected by centrifuging the blood at 2,300 × g at 4°C for 10 min ( 74 ). The liver tissues were also excised under anesthetic conditions, and the serum and liver tissues were stored at -80°C prior to further experimentation.…”