Key result
Astragaloside IV administration alleviated the severity of CVB3-induced myocarditis and attenuated cardiac inflammation by increasing A20 expression and inhibiting NF-κB signaling.
Why the study?
Does Astragaloside IV improve CVB3-induced myocarditis?
Does Astragaloside IV improve CVB3-induced myocarditis?
Astragaloside IV alleviates CVB3-induced myocarditis by up-regulating A20 expression and inhibiting NF-κB signalling, providing a potential therapeutic target.
AST-IV attenuates CVB3 myocarditis severity in mice via A20; leaves open clinical translation in human viral myocarditis.
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 (C41 H68 O14 , 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.
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Gui et al. (2015) studied CVB3-induced myocarditis. Astragaloside IV (AST-IV) was evaluated on Severity of myocarditis and cardiac inflammation. Astragaloside IV administration alleviated the severity of CVB3-induced myocarditis and attenuated cardiac inflammation by increasing A20 expression and inhibiting NF-κB signaling.
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