Abstract
Viral myocarditis (VMC) most prevalently caused by coxsackievirus B3 (CVB3) infection is characterized by severe cardiac inflammation. Therapeutic options for the disease are still limited. Astragaloside IV (AST-IV), a purified small molecular saponin (C41H68O14, MW 784), is the main active component of Chinese medical herb Astragalus which has been empirically prescribed for the treatment of heart dysfunction for centuries. In this study, we investigated the effect of AST-IV on CVB3-induced myocarditis and explored its possible mechanism involved. The results showed that AST-IV administration alleviated the severity of myocarditis and attenuated cardiac inflammation, which was mediated by inhibition of nuclear factor-kappaB (NF-κB) signalling. Importantly, we further identified that the inhibitory effect of AST-IV on NF-κB signalling was through increasing A20 (TNFAIP3) expression. Moreover, we validated that A20 was critical for the therapeutic efficacy of AST-IV on CVB3-induced myocarditis. Finally, we revealed that AST-IV enhanced A20 expression at post-transcriptional level by stabilization of mRNA. Our findings uncover a previously unknown mechanism for AST-IV in the treatment of VMC because of modulating inflammatory response via increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC.
Highlights
Viral myocarditis (VMC) characterized by myocardial inflammation represents one of the most challenging clinical problems in cardiology, associated with a broad spectrum of pathological triggers and a wide range of clinical presentations that vary from mild dyspnoea to acute heart failure
We investigated the effect of Astragaloside IV (AST-IV) on coxsackievirus B3 (CVB3)-induced myocarditis
The results showed that CVB3 infected mice without AST-IV treatment underwent a dramatic and continuous loss of bodyweight as maximal to 29.7%, and more than 70% mice died within 10 days post infection
Summary
Viral myocarditis (VMC) characterized by myocardial inflammation represents one of the most challenging clinical problems in cardiology, associated with a broad spectrum of pathological triggers and a wide range of clinical presentations that vary from mild dyspnoea to acute heart failure. The dominant aetiology of VMC is considered to be the enteroviruses of picornavirus family, with coxsackievirus B3 (CVB3) being the most common one, and the same virus strain induced similar inflammatory heart. There is no specific therapy for VMC patients, though extensive investigations on therapeutic approaches have been conducted. Several proposed clinical treatment strategies that target specific points were reported, including the application of immunosuppressive agents (azathioprine, prednisone and cyclosporine) [8,9,10], intravenous immunoglobulin which may replace antibodies, neutralize pathogens and enhance clearance of inflammatory cytokines that contribute to myocytes destruction [11, 12], and antiviral agents, such as interferons and pleconaril, which may target the causative organism, possibly halting the cascade of myocyte destruction [13,14,15].
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