Hesperetin ameliorates cardiac inflammation and cardiac fibrosis in streptozotocin-induced diabetic rats by inhibiting NF-κB signaling pathway

Objective: Activation of several signal transduction pathways, including cardiac inflammation and fibrosis, are important parts of structural and functional changes in diabetic cardiomyopathy (DCM), which is a leading cause of cardiovascular complications. NF-kappa B signaling pathway plays critical roles in promoting cardiac inflammation and cardiac fibrosis. It has been reported that hesperetin could inhibit cardiac remodelling induced by pressure overload in mice. However, it is still not clear whether and how hesperetin plays a role in cardiac inflammation and fibrosis in diabetic rats. Methods: Diabetes mellitus (DM) was induced by streptozotocin (70 mg/kg body weight). Rats were received hesperetin (30 mg/kg/day) for 12 weeks. Effect of hesperetin on glycemic parameters was detected with blood glucose, glycated hemoglobin (HbA1c). After induction of diabetes, all rats were underwent echocardiography to evaluate cardiac function. Expressions of inflammation markers such as TNF-alpha, IL-1 beta, ICAM-1 and VCAM-1 were investigated by real-time PCR, gene expression of fibrosis markers such as collagen I and III, and histological analysis were applied to determine the level of cardiac fibrosis. NF-kappa B signaling pathway activation was also detected by western blot. Results: Hesperetin reduced expression levels of TNF-alpha, IL-1 beta, ICAM-1, VCAM-1, collagen I and III. The level of collagen deposition in diabetic myocardium was attenuated with the treatment of hesperetin. Additionally, administration of hesperetin inhibited activation of NF-kappa B signaling pathway. Conclusion: These results demonstrate that hesperetin inhibited cardiac inflammation and cardiac fibrosis post-diabetes through blocking NF-kappa B signaling pathway, which could be a key mechanism of hesperetin in attenuating cardiac remodeling in diabetic rats.