Daucosterol alleviates heart failure with preserved ejection fraction through activating PPARα pathway

Heart failure with preserved ejection fraction (HFpEF) has been increasing in the population in recent years and is mainly characterized by preserved left ventricle ejection fraction (LVEF), diastolic dysfunction and systemic inflammation. Daucosterol (DAU), a glycoside of β-sitosterol, has good anti-inflammatory and antioxidative properties; however, its effects and mechanisms in HFpEF have not been investigated. To detect whether DAU could alleviate HFpEF, C57BL/6J male mice were fed with N-nitro-l-arginine methyl ester (L-NAME) in drinking water and high fat diet (HFD) and treated with DAU by gavage (i.g.) for 10 weeks. The results showed that DAU treatment significantly alleviated HFpEF in mice. Mechanistically, by controlling PPARα and preventing NF-κB phosphorylation, DAU reduced oxidative stress and the inflammatory response. In conclusion, our study provides a new clue for natural product DAU in alleviating HFpEF.