Auricularia auricula polysaccharides attenuate ventricular remodeling in mice by suppressing oxidative stress and apoptosis via activation of the Keap1/Nrf2/HO-1 pathway

Ventricular remodeling (VR) represents a critical pathological process in heart failure, for which therapeutic strategies remain limited. Auricularia auricula , an edible and medical fungus, contains bioactive polysaccharides (AAP), but its role in VR is unclear. This study investigated the cardioprotective effects and underlying mechanism of AAP on isoproterenol (ISO)-induced VR. Structural analysis revealed AAP as a porous aggregated polysaccharide. In vivo , AAP (100 and 150 mg/kg) significantly improved cardiac function and attenuated myocardial hypertrophy, fibrosis, and ultrastructural damage in ISO-challenged mice. Mechanistically, AAP suppressed oxidative stress (reducing MDA/ROS, enhancing GSH/SOD) and cardiomyocyte apoptosis (decreasing TUNEL + cells and cleaved caspase-3). Proteomic profiling and molecular validation demonstrated that AAP consistently activated the Keap1/Nrf2/HO-1 pathway, promoting Nrf2 nuclear translocation while downregulating Keap1 both in vivo and in ISO-stimulated H9C2 cells. These findings identify AAP as a potential functional food ingredient for preventing pathological cardiac remodeling through modulation of antioxidant defense. • AAP alleviates ISO-induced cardiac dysfunction and structural remodeling in mice. • Proteomics and molecular assays confirm AAP activates the Keap1/Nrf2 antioxidant pathway. • AAP inhibits cardiomyocyte apoptosis, oxidative stress and fibroblast activation. • AAP shows potential as functional food ingredient for preventing pathological cardiac remodeling.