Active component and protective effects of Cornus officinalis on cardiomyocyte hypertrophy via AMPK

Background Chronic heart failure (CHF) is characterized by pathological cardiac remodeling and metabolic dysfunction, with cardiomyocyte hypertrophy as a key cellular process driving disease progression. Cornus officinalis Sieb. et Zucc. (Cor) has demonstrated cardioprotective effects in heart failure, yet its cellular mechanisms in relation to cardiomyocyte hypertrophy remain poorly defined. Methods Initial in vivo cardiac tissue analysis assessed Cor-associated alterations in AMP-activated protein kinase (AMPK)-related metabolic gene expression. Following this, in vitro studies employed an isoproterenol (ISO)-induced H9C2 cell hypertrophy model. Evaluations included cellular hypertrophy and intracellular reactive oxygen species (ROS) accumulation, with AMPK-related signaling and metabolic regulators analyzed via western blotting and RT-qPCR. Molecular docking predicted potential interactions between key constituents of Cor and AMPK, while CCK-8 assays assessed the effects on H9C2 cell viability. Results In cardiac tissues from heart failure rats, Cor mitigated the upregulation of AMPK-related metabolic genes observed in the Model group, significantly decreasing mRNA levels of FAS, G6Pase, cyclin D1, and SREBP1c (all P < 0.05). These effects were partially reversed by dorsomorphin (Dor, an AMPK inhibitor). In H9C2 cells, Cor-containing serum diminished ISO-induced cellular hypertrophy (p < 0.01) and intracellular ROS accumulation (p < 0.0001), while increasing the p-AMPK/AMPK ratio (P < 0.0001). Concurrently, G6Pase expression decreased, and PGC-1α levels increased (both P < 0.001). Dor treatment partially reversed these effects (both p < 0.05), indicating the involvement of AMPK-related signaling. Molecular docking analysis suggested a potential interaction between cornuside and AMPK (−7.9 kcal/mol), and cell viability assays identified cornuside (40 μM) as a candidate bioactive component contributing to Cor's protective effects (p < 0.05). Conclusion The findings of this study indicate that Cor provides protective effects against ISO-induced H9C2 cell hypertrophy, which are associated with the modulation of AMPK-related metabolic signaling and a reduction in intracellular ROS accumulation. Initial in vivo observations, supported by subsequent in vitro evidence, highlight a potential role for AMPK signaling in the effects of Cor. However, further validation is necessary to establish direct causality and target engagement. Cornuside may be a key bioactive constituent contributing to these protective effects.