Abstract
Heart failure with preserved ejection fraction (HFpEF), a complex disease that is increasingly prevalent due to population aging, pose significant challenges in its treatment. The present study utilized the HFpEF rat model and H9C2 cells as research subjects to thoroughly investigate the potential mechanisms of alarin in protecting cardiac function in HFpEF. The study shows that under HFpEF conditions, oxidative stress significantly increases, leading to myocardial structural damage and dysfunction of calcium ion channels, which ultimately impairs diastolic function. Alarin, through its interaction with NADPH oxidase 1 (NOX1), effectively alleviates oxidative stress and modulates the activities of type 2 ryanodine receptor (RyR2) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2), thereby facilitating the restoration of Ca2+ homeostasis and significantly improving cardiac function in the HFpEF model. This research not only uncovers the cardioprotective effects of alarin and its underlying molecular mechanisms but also provides new insights and potential therapeutic targets for HFpEF treatment strategies, suggesting a promising future for alarin and related therapies in the management of this debilitating condition.