Biochemical and biophysical research communications · 2025
Astragaloside IV regulates the IRF7/NLRP3 axis to inhibit neutrophil extracellular trap formation and alleviate coxsackievirus B3-induced myocarditis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Min, Cheng Xiaobin, Chen Miaoqi, Qin Rui, Dong Qiufen, Li Gang
Аннотация
BACKGROUND: Coxsackievirus B3 (CVB3) infection is a common cause of myocarditis, and the resulting inflammatory response and cellular damage can lead to severe cardiac dysfunction. Astragaloside IV (AS-IV), a natural compound with anti-inflammatory and antiviral properties, has shown potential therapeutic value in various inflammatory and immune-related diseases. Our study aims to explore the potential effects and underlying mechanisms of AS-IV in CVB3-induced viral myocarditis (VMC).
METHODS: An animal model of VMC was established by infecting C57BL/6 mice with CVB3. Histopathological examinations, inflammatory cytokine levels, cardiac injury markers, fibrosis levels, cardiac function parameters, and neutrophil markers were assessed to evaluate the effects of AS-IV on the regulation of the Interferon regulatory factor 7 (IRF7)/Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) axis and neutrophil extracellular traps (NETs) formation about myocardial inflammation and cardiac damage.
RESULTS: AS-IV attenuated CVB3-induced myocardial fibrosis and inflammation in mice, preserving cardiac function. Mechanistically, AS-IV promoted cardiac recovery by reducing NLRP3 inflammasome activation and ameliorating fibrosis and inflammatory responses. Moreover, overexpression of IRF7 enhanced NLRP3 expression, increased NETs formation, and exacerbated fibrosis and inflammation, resulting in greater myocardial cell damage. However, the effects of IRF7 overexpression on myocardial cells were reversed when a PAD4 inhibitor was added to suppress NETs formation.
CONCLUSION: AS-IV mitigates CVB3-induced myocarditis in mice by regulating the IRF7/NLRP3 axis to inhibit NETs formation. This study reveals the potential therapeutic role of AS-IV in the treatment of VMC and provides a theoretical basis and experimental support for the development of new antiVMC medications.
METHODS: An animal model of VMC was established by infecting C57BL/6 mice with CVB3. Histopathological examinations, inflammatory cytokine levels, cardiac injury markers, fibrosis levels, cardiac function parameters, and neutrophil markers were assessed to evaluate the effects of AS-IV on the regulation of the Interferon regulatory factor 7 (IRF7)/Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) axis and neutrophil extracellular traps (NETs) formation about myocardial inflammation and cardiac damage.
RESULTS: AS-IV attenuated CVB3-induced myocardial fibrosis and inflammation in mice, preserving cardiac function. Mechanistically, AS-IV promoted cardiac recovery by reducing NLRP3 inflammasome activation and ameliorating fibrosis and inflammatory responses. Moreover, overexpression of IRF7 enhanced NLRP3 expression, increased NETs formation, and exacerbated fibrosis and inflammation, resulting in greater myocardial cell damage. However, the effects of IRF7 overexpression on myocardial cells were reversed when a PAD4 inhibitor was added to suppress NETs formation.
CONCLUSION: AS-IV mitigates CVB3-induced myocarditis in mice by regulating the IRF7/NLRP3 axis to inhibit NETs formation. This study reveals the potential therapeutic role of AS-IV in the treatment of VMC and provides a theoretical basis and experimental support for the development of new antiVMC medications.