Background: Oxidative stress plays a pivotal role in the pathogenesis of heart failure and is closely linked to myocardial remodeling, which includes myocardial hypertrophy and fibrosis. Chrysin (CHR) has multiple medicinal effects such as antioxidant, anti-inflammatory, and anti-apoptosis. This research seeks to investigate whether CHR can protect against pressure overload–induced myocardial remodeling and to explore the underlying mechanism.
Methods: Transverse aortic constriction (TAC) surgery was conducted to establish a model of cardiac hypertrophy on male C57BL/6J mice. A model of cardiomyocyte hypertrophy in H9C2 cells induced by angiotensin II (Ang II) was also established.
Results: The results showed that CHR significantly improved survival and cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited the expression of inflammatory mediators TNF-α and IL-1β, suppressed cell apoptosis rate, downregulated the levels of Bcl-2 Associated X protein (BAX) and Cleaved-Caspase-3, and upregulated B-cell lymphoma/leukemia 2 (BCL-2) expression in TAC surgical mice or Ang II-treated H9C2 cells. CHR could also upregulate the levels of antioxidant enzymes SOD1 and HO-1 by mediating the nuclear translocation and expression of NRF2 to counteract oxidative stress response. The further mechanism investigation utilizing bioinformatics analysis and western blot revealed that the disease of heart failure is associated with the phosphatidylinositol-3-kinase (PI3K)/serine/threonine-protein kinase B (AKT) signaling pathway.
Conclusions: Collectively, our findings demonstrated that CHR might exert the improvement effects on pressure overload–induced myocardial remodeling with hypertrophy and fibrosis through regulating the PI3K/AKT/NRF2 pathway–mediated oxidative stress response to alleviate myocardial cell inflammation and apoptosis, suggesting that CHR may be a promising therapeutic agent for cardiac diseases induced by pressure overload.
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2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences
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