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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.