Chelidonic Acid Monohydrate Attenuates Isoproterenol-Induced Myocardial Infarction via Modulation of Nuclear Factor Erythroid 2-Related Factor 2/Nuclear Factor Kappa B–Mediated Oxidative Stress and Inflammation

Abstract This study aimed to assess the cardioprotective activity of chelidonic acid monohydrate in an isoproterenol-induced myocardial infarction model in rats. Chelidonic acid monohydrate was administered orally at doses of 5, 10, and 20 mg/kg for 7 days, and its effects were evaluated using hemodynamic, electrocardiographic, morphometric, biochemical, and histopathological parameters. Chelidonic acid monohydrate demonstrated significant cardioprotective activity at doses of 10 and 20 mg/kg, as evidenced by improvements in hemodynamic and biochemical parameters, along with attenuation of structural changes such as cardiac hypertrophy and the normalization of electrocardiographic patterns. Treatment with chelidonic acid monohydrate also significantly reduced myocardial injury and fibrosis. Furthermore, chelidonic acid monohydrate modulated oxidative stress and inflammatory pathways as indicated by increased levels of antioxidant enzymes (superoxide dismutase and catalase) and decreased levels of pro-inflammatory mediators (nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6). Molecular docking studies confirmed strong binding affinities of chelidonic acid monohydrate to key myocardial infarction–related targets, including nuclear factor erythroid 2–related factor 2, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6, with binding free energy values of−7.84,−7.59,−6.12, and−6.41 kcal/mol, respectively. Overall, these findings suggest that the cardioprotective effects of chelidonic acid monohydrate are mediated through modulation of the nuclear factor erythroid 2–related factor 2/nuclear factor kappa B pathway. This study provides compelling evidence supporting chelidonic acid monohydrate as a potential therapeutic agent for myocardial infarction, warranting further studies to assess its long-term efficacy.