Saponarin: a shield against coronary heart disease-related myocardial injury via NF-κB pathway inhibition

Objective Coronary heart disease (CHD) is a major cardiovascular disorder characterized by myocardial ischemia and injury. Saponarin is a natural flavonoid glycoside with anti-inflammatory and tissue-protective activities. This study evaluated the protective effect of saponarin against CHD-related myocardial injury and explored the potential involvement of the NF-κB signaling pathway. Methods H9C2 cells were exposed to DOX alone or co-treated with saponarin. Cell viability was assessed using CCK-8, and LDH release was used to assess cell injury. Cell apoptosis was assessed by flow cytometry and cleaved caspase-3 expression using western blotting. Inflammatory responses were evaluated by measuring IL-1 β and IL-6 mRNA expression using RT-qPCR. NF-κB pathway activity was assessed by western blotting and immunofluorescence staining, and rescue experiments were performed using the NF-κB pathway activator RANKL. In addition, a CHD rat model induced by high-fat emulsion combined with pituitrin administration was used to evaluate the in vivo cardioprotective effect of saponarin. Cardiac function was assessed by echocardiography, myocardial infarct area was evaluated by TTC staining, myocardial histopathological injury was examined by HE staining, myocardial apoptosis was detected by TUNEL staining. Results Saponarin improved DOX-induced H9C2 cell injury, as reflected by increased cell viability and reduced LDH release. Saponarin also reduced apoptosis, cleaved caspase-3 expression, and IL-1 β and IL-6 mRNA expression in DOX-treated H9C2 cells. In CHD rats, saponarin improved cardiac function, reduced myocardial infarct area, alleviated myocardial histopathological injury, and decreased serum CK, CK-MB, LDH, and cTnT levels. In addition, saponarin reduced myocardial apoptosis and inflammatory factor expression in CHD rats. Given the reported regulatory effect of saponarin on NF-κB p65 and the role of NF-κB p65 in myocardial injury, NF-κB signaling was further investigated. Mechanistically, saponarin decreased p-I κ B α /I κ B α and p-NF-κB/NF-κB ratios and reduced NF-κB p65 nuclear translocation. RANKL-mediated NF-κB pathway activation partially attenuated the protective effects of saponarin against DOX-induced H9C2 cell injury. Conclusion Saponarin alleviated CHD-related myocardial injury, ameliorated cardiac dysfunction, and attenuated apoptosis and inflammatory responses. These protective effects may involve suppression of NF-κB signaling.