Icariside II alleviates heart failure in mice by modulating Wnt/β-catenin and mitochondrial apoptotic pathways

Heart failure (HF) represents a major global health challenge, characterized by progressive cardiac dysfunction and remodeling. Current standard-of-care treatments often fall short in fully addressing the underlying pathological mechanisms, such as ventricular remodeling and apoptosis. A key signaling mechanism, the Wnt/β-catenin pathway, is closely linked to HF dysregulation, alongside mitochondrial apoptotic pathways that drive cell death in stressed cardiomyocytes. Understanding and targeting these pathways offers a promising avenue for novel therapeutic interventions to prevent or reverse HF progression.

Using an isoproterenol (ISO)-induced mice model of HF and H9c2 cell injury, researchers investigated the effects of Icariside II on cardiac function, ventricular remodeling, and apoptosis. The study focused on the Wnt/β-catenin and mitochondrial apoptotic pathways. Key endpoints included cardiac function assessment, measurement of left ventricular hypertrophy, and expression levels of HF markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). In vitro, H9c2 cells were subjected to ISO-induced injury, with cell area and apoptosis evaluated. The role of GSK-3β was probed using the inhibitor SB216763 to reverse observed effects.

Icariside II significantly improved cardiac function in the ISO-induced HF mouse model. It effectively reduced left ventricular hypertrophy and decreased the expression of HF markers, specifically atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Western blot analysis of cardiac tissue from Icariside II-treated HF mice revealed reduced levels of both Wnt/β-catenin pathway proteins and apoptotic markers. > Consistent with in vivo findings, Icariside II also protected H9c2 cells from ISO-induced injury in vitro, leading to a decrease in cell area and apoptosis. This cellular protection was accompanied by a similar suppression of Wnt/β-catenin pathway proteins. Crucially, the GSK-3β inhibitor SB216763 reversed Icariside II's protective effects, increasing H9c2 cell apoptosis and restoring Wnt/β-catenin pathway activity (except for Wnt3A), thereby confirming the pathway's involvement.