Anti–viral effects of curcumin on influenza A virus–induced myocarditis via inhibiting Wnt/β–catenin signaling

Influenza A virus (IAV) is a widespread human pathogen which plays an important role in the development and exacerbation of myocarditis and causes a significant impairment of the cardiac function and even mortality. Curcumin is an important component of traditional Chinese and Indian medicine with well-documented anti-inflammatory effects to prevent the cardiovascular disease. However, no study to date has addressed the effects and possible mechanism of curcumin on IAV-induced myocarditis in mice. In this study, a mouse model was firstly established for the study of IAV-induced myocarditis. H1N1-infected mice were apparently ill with lethargy, poor coat condition, anorexia, irritability, back arching and even survival. After treatment with curcumin (100 mg/kg/day), the weight loss and survival rate were ameliorated throughout the study. On day 5 after infection, both the heart weight to body weight ratio and the left ventricular weight to body weight ratio were significantly decreased in mice treated with curcumin. The area of myocardial necrosis was significantly smaller in the hearts of mice treated with curcumin compared to IVA-infected mice. Gene expression of NS1, TNF-α, IL-6 and IL-1β, I collagen, and MMP-2 mRNA in the heart tissue was markedly increased in IAV-infected mice, while curcumin significantly attenuated the expression of these genes. RT-PCR analysis revealed that curcumin inhibited the mRNA expression of Wnt3, Tcf4 and β-catenin. Curcumin also suppressed mRNA levels of Wnt target genes, c-Myc and cyclin D1. Our results provided the first evidence for the effect of curcumin to treat IVA-induced myocardial damage in particular via inhibiting Wnt/β-catenin signaling.