Hesperetin protects against cardiac remodelling induced by pressure overload in mice

Area of Science:

• Cardiovascular Biology
• Pharmacology
• Natural Products Chemistry

Background:

• Cardiac remodelling, characterized by hypertrophy, fibrosis, oxidative stress, and apoptosis, is a key factor in heart failure (HF).
• Hesperetin, a citrus flavonoid found abundantly in oranges, exhibits various pharmacological activities, but its impact on cardiac remodelling is not well understood.

Purpose of the Study:

• To investigate the therapeutic potential of hesperetin in mitigating cardiac remodelling induced by pressure overload.
• To elucidate the underlying molecular mechanisms by which hesperetin exerts its cardioprotective effects.

Main Methods:

• Aortic banding (AB) mouse model was employed to induce pressure overload and cardiac remodelling.
• Mice were administered hesperetin orally, and cardiac function, hypertrophy, fibrosis, oxidative stress, and apoptosis were assessed.
• Key signaling pathways including PKCα/βII-AKT, JNK, and TGFβ1-Smad were analyzed to determine the mechanism of action.

Main Results:

• Hesperetin administration significantly attenuated cardiac hypertrophy, fibrosis, and dysfunction in AB mice, as evidenced by multiple physiological and histological parameters.
• Hesperetin effectively reduced oxidative stress and myocyte apoptosis associated with pressure overload.
• The cardioprotective effects were mediated through the inhibition of PKCα/βII-AKT, JNK, and TGFβ1-Smad signaling pathways.

Conclusions:

• Hesperetin demonstrates significant protective effects against cardiac remodelling induced by pressure overload.
• The study highlights hesperetin's ability to inhibit cardiac hypertrophy, fibrosis, oxidative stress, and myocyte apoptosis.
• Hesperetin shows promise as a potential therapeutic agent for managing cardiac remodelling and heart failure.