Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation.
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.
Institute for Immunobiology, Shanghai Medical College, Fudan University, Shanghai, China.
Jun
J
Gui
Ruizhen
R
Chen
Wei
W
Xu
Sidong
S
Xiong
D000818:Animals; D015153:Blotting, Western; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D003546:Cysteine Endopeptidases / Q000235:genetics*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004452:Echocardiography; D004770:Enterovirus / Q000187:drug effects* / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006321:Heart / Q000187:drug effects / Q000503:physiopathology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D015854:Up-Regulation / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse
A20; Astragaloside IV; CVB3; NF-κB; Viral myocarditis