Hyperlipidemia is an important
lipid disorder and a risk factor for health.
Aspirin eugenol ester (AEE) is a novel synthetic compound which is made up of two chemical structural units from
aspirin and
eugenol.
Therapeutic effect of AEE on
hyperlipidemia has been confirmed in animal model. But the action mechanism of AEE on
hyperlipidemia is still poorly understood. In this study, we investigated the effects of AEE on liver and feces metabolic profile through UPLC-Q-TOF/MS-based untargeted metabolomics in
hyperlipidemia hamster induced with high fat diet (HFD), and the effects of AEE on the expression of genes and
proteins related to
cholesterol and
bile acid (BA) in HFD-induced
hyperlipidemia SD rat. The concentrations of 26
bile acids (BAs) in the liver from
hyperlipidemia SD rat were also quantified with the application of BA targeted metabolomics. The results of untargeted metabolomics showed that the underlying mechanism of AEE on
hyperlipidemia was mainly associated with
amino acid metabolism,
glutathione metabolism, energy metabolism, BA metabolism, and
glycerophospholipid metabolism. AEE induced the expression of the BA-synthetic
enzymes cholesterol 7α-hydroxylase (CYP7A1) by the inhibition of BA
nuclear receptor farnesoid X receptor (FXR) in liver, which resulted in accelerating the conversion of
cholesterol into
bile acids and excrete in feces. The results of BA targeted metabolomics showed that AEE elevated the
glycine-conjugated BA level and decreased the tauro-conjugated BA level. In conclusion, this study found that AEE decreased FXR and increased CYP7A1 in the liver, which might be the possible molecular mechanisms and targets of AEE for anti-
hyperlipidemia therapies.