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2015 ; 19
(4
): 850-64
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Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires
A20 (TNFAIP3) up-regulation
#MMPMID25728713
Gui J
; Chen R
; Xu W
; Xiong S
J Cell Mol Med
2015[Apr]; 19
(4
): 850-64
PMID25728713
show ga
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-?B) signalling. Importantly, we further identified
that the inhibitory effect of AST-IV on NF-?B 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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