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

Area of Science:

• Cardiology
• Pharmacology
• Biochemistry

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a growing health concern characterized by preserved left ventricle ejection fraction (LVEF), diastolic dysfunction, and systemic inflammation.
• Daucosterol (DAU), a natural glycoside of β-sitosterol, possesses known anti-inflammatory and antioxidative properties.
• The therapeutic potential of DAU in HFpEF remains unexplored.

Purpose of the Study:

• To investigate the efficacy of Daucosterol (DAU) in alleviating HFpEF.
• To elucidate the underlying molecular mechanisms by which DAU exerts its effects in a preclinical HFpEF model.

Main Methods:

• C57BL/6J male mice were induced with HFpEF using N-nitro-l-arginine methyl ester (L-NAME) and a high-fat diet (HFD).
• Mice were treated with Daucosterol (DAU) via oral gavage for 10 weeks.
• Key molecular pathways including PPARα and NF-κB phosphorylation were analyzed to assess oxidative stress and inflammation.

Main Results:

• DAU treatment significantly ameliorated HFpEF symptoms in the mouse model.
• DAU administration effectively reduced oxidative stress and inflammatory responses.
• Mechanistically, DAU modulated PPARα activity and inhibited NF-κB phosphorylation.

Conclusions:

• Daucosterol (DAU) demonstrates significant therapeutic potential for mitigating HFpEF.
• DAU's mechanism involves the reduction of oxidative stress and inflammation via PPARα and NF-κB pathways.
• This study identifies Daucosterol as a promising natural product for future HFpEF therapeutic development.