aspirin-eugenol-ester and Body-Weight

Based 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.. Suspension 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.. In 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.. Anti-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.

Topics: Administration, Oral; Amino Acids; Animals; Aspirin; Bile Acids and Salts; Body Weight; Cholesterol, LDL; Diet, High-Fat; Eugenol; Fatty Acids; Feces; Glycerophospholipids; Hyperlipidemias; Hypolipidemic Agents; Lipid Metabolism; Liver; Male; Metabolome; Principal Component Analysis; Purines; Rats; Rats, Sprague-Dawley; Triglycerides

The subchronic toxicity of aspirin eugenol ester (AEE) was evaluated after 15-day intragastrically administration in rats at daily doses of 50, 1000, and 2000 mg/kg. AEE at low-dose showed no toxicity to the tested rats. Following repeated exposure to medium- or high-dose of AEE, apparent changes were observed in the levels of blood glucose, AST, ALP, ALT and TB in both male and female rats, and appeared to be dose-independent. There were no significant gender differences in most indexes of subchronic toxicity throughout the experimental period with the exception of food consumption and body weight. The no-observed-adverse-effect level (NOAEL) of AEE was considered to be 50 mg/kg/day under the present study conditions.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Aspirin; Bilirubin; Blood Cell Count; Blood Chemical Analysis; Blood Glucose; Body Weight; Eating; Eugenol; Female; Intubation, Gastrointestinal; Liver Function Tests; Male; No-Observed-Adverse-Effect Level; Organ Size; Rats; Rats, Wistar; Tissue Fixation