Astragaloside IV prevents enterovirus 71-induced pyroptosis through the TCF12-TXNIP-Keap1/Nrf2 axis

[Display omitted] •AST-IV is a food or dietary ingredient with excellent disease prevention potential.•AST-IV has been used to treat inflammation.•AST-IV inhibited EV71 induced-pyroptosis.•AST-IV inhibited EV71 induced-pyroptosis through the TCF12-TXNIP-Keap1/Nrf2 axis. This study aimed to investiga...

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Published inJournal of functional foods Vol. 118; p. 106290
Main Authors Hao, JinFang, Zhang, Xiaoyan, Wang, Hui, Du, Jianping, Han, Qian, Sun, Chenxi, Li, Qingshan
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 01.07.2024
Elsevier
Subjects
Astragaloside IV
Enterovirus 71
Keap1/Nrf2 signaling
Pyroptosis
Thioredoxin interacting protein
Transcription factor 12
PBS
Enterovirus 71
Pyroptosis
Keap1/Nrf2 signaling
Thioredoxin interacting protein
DAPI
EV71
Astragaloside IV
AM
TCID50
GES-1
PCD
DMEM
SARS-CoV2
Transcription factor 12
RD
HFMD
TXNIP
AST-IV
TRX
CVB3
HBV
EB
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Summary:[Display omitted] •AST-IV is a food or dietary ingredient with excellent disease prevention potential.•AST-IV has been used to treat inflammation.•AST-IV inhibited EV71 induced-pyroptosis.•AST-IV inhibited EV71 induced-pyroptosis through the TCF12-TXNIP-Keap1/Nrf2 axis. This study aimed to investigate the inhibitory effect of astragaloside IV (AS-IV) on enterovirus 71 (EV71)-induced pyroptosis. The results indicated that AST-IV inhibited EV71-induced pyroptosis in normal human gastric epithelial (GES-1) cells. Therefore, we investigated the mechanisms underlying pyroptosis inhibition by AST-IV. We found that EV71 inhibited the Nrf2-Keap1 pathway, whereas AST-IV treatment activated it. Overexpression of Nrf2 led to the inhibition of EV71-induced pyroptosis. EV71 infection and AST-IV treatment upregulated and downregulated thioredoxin interacting protein (TXNIP), respectively. Downregulation of TXNIP activated the Keap1/Nrf2 signaling pathway and inhibited EV71-induced pyroptosis. Furthermore, transcription factor 12 (TCF12) reduced the protein and mRNA levels of TXNIP, and AST-IV treatment upregulated TCF12. These results demonstrate that the TCF12-TXNIP-Keap1/Nrf2 axis participates in the inhibition of pyroptosis by AST-IV in EV71-infected GES-1 cells, suggesting that AST-IV could be used as a dietary supplement to alleviate EV71-induced pyroptosis.
ISSN:1756-4646
2214-9414
DOI:10.1016/j.jff.2024.106290