Influence of Cinnamaldehyde on Viral Myocarditis in Mice

Introduction: This study was designed to examine the effects of cinnamaldehyde on coxsackievirus B-3 (CVB3)-induced viral myocarditis (VMC) and underlying signaling, with a focus on the toll-like receptor (TLR)4-nuclear factor (NF)-kappa B pathway. Methods and Results: The antiviral and myocardial effects of cinnamaldehyde and its metabolite cinnamic acid were evaluated both in vitro and in vivo. Our results showed that cinnamic acid but not cinnamaldehyde reduced the viral titer in CVB3-infected myocardial cells. Our in vivo study demonstrated that intraperitoneal injection of either cinnamaldehyde or cinnamic acid significantly enhanced the survival rate and reduced myocardial viral titer in VMC mice compared with CVB3-infected controls (P < 0.05). There was no significant difference in effectiveness between the cinnamic acid and the cinnamaldehyde groups (P < 0.05). Cinnamaldehyde reduced plasma nitric oxide (NO) content, NF-kappa B, inducible nitric oxide synthase and TLR4 expression and decreased inflammatory cell infiltrate in myocardium from VMC mice 7 days after viral inoculation (P < 0.05). However, these effects were not observed with cinnamic acid treatment. Statistical significance was present between cinnamic acid and cinnamaldehyde in their effects on plasma NO content, NF-kappa B, inducible nitric oxide synthase and TLR4 expression (P < 0.05). Conclusion: Our data suggest that although cinnamaldehyde has antiviral effects on VMC through its metabolite, cinnamic acid, it directly reduces the inflammation in VMC by inhibiting the TLR4-NF-kappa B signal transduction pathway.