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)-κB 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)-α,
interleukin (IL)-1β and
IL-6 were assessed by reverse-transcription quantitative PCR and ELISA, and activation of the NF-κB signaling pathway was detected by western blot analysis. It was found that
hesperetin reduced the expression levels of TNF-α, IL-1β,
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-κB signaling pathway. These findings indicated that
hesperetin may inhibit cardiac
inflammation post-MI through blocking the NF-κB signaling pathway, which may be a key mechanism via which
hesperetin attenuates cardiac
fibrosis.