Remission of CVB3‐induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up‐regulation. Issue 4 (1st March 2015)

• Record Type: Journal Article
• Authors: Gui, Jun; Chen, Ruizhen; Xu, Wei; Xiong, Sidong
• Is Part Of: Journal of cellular and molecular medicine. Volume 19:Issue 4(2015)
• Page Start: 850
• Page End: 864
• Publication Date: 2015-03-01
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12459
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12459-abs-0001"> <title>Abstract</title> <p>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 (C<sub>41</sub>H<sub>68</sub>O<sub>14</sub>, 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 <italic>via</italic> increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC.</p> </abstract>