Hesperetin protects against inflammatory response and cardiac fibrosis in postmyocardial infarction mice by inhibiting nuclear factor κB signaling pathway

Cardiac inflammation and cardiac fibrosis are important parts of cardiac remodeling following myocardial infarction (MI), which may be the basic mechanisms of the development of chronic heart failure. The nuclear factor (NF)-kappa B signaling pathway promotes cardiac inflammation and fibrosis. It has reported that hesperetin inhibits cardiac remodeling induced by pressure overload in mice. However, it has remained elusive whether and how hesperetin has a role in cardiac fibrosis post-MI. Therefore, a mouse model of MI was established by left anterior descending coronary artery ligation. Mice received hesperetin (30 mg/kg/day) or vehicle after surgery. After 8 weeks, all mice underwent echocardiography to evaluate cardiac function. Gene expression of cardiac fibrosis markers such as connective tissue growth factor (CTGF) as well as collagen I and III, and histological analysis were applied to determine the level of cardiac fibrosis. The expression of inflammatory markers such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 were assessed by reverse-transcription quantitative PCR and ELISA, and activation of the NF-kappa B signaling pathway was detected by western blot analysis. It was found that hesperetin reduced the expression levels of TNF-alpha, IL-1 beta, IL-6 and CTGF as well as collagen I and III. The level of collagen deposition in post-MI myocardium was attenuated with the treatment of hesperetin. In additionally, administration of hesperetin inhibited the activation of the NF-kappa B signaling pathway. These findings indicated that hesperetin may inhibit cardiac inflammation post-MI through blocking the NF-kappa B signaling pathway, which may be a key mechanism via which hesperetin attenuates cardiac fibrosis.