Activation of AMPK-dependent SIRT-1 by astragalus polysaccharide protects against ochratoxin A-induced immune stress in vitro and in vivo

Int J Biol Macromol. 2018 Dec;120(Pt A):683-692. doi: 10.1016/j.ijbiomac.2018.08.156. Epub 2018 Aug 28.

Abstract

Recent studies have highlighted the immune stress caused by ochratoxin A (OTA), but little attention was paid to its alleviation. In the present study, the protective effects of astragalus polysaccharide (APS) against OTA-induced immune stress in vitro and in vivo and its mechanism/(s) involved were investigated. The in vitro results showed that APS (20 μg/ml) induced a significant decrease in cytotoxicity, apoptosis and pro-inflammatory cytokine expressions elevated by OTA (1.5 μg/ml) in porcine alveolar macrophages (PAMs). In vivo, APS (200 mg/kg b.w.) significantly alleviated OTA-induced (75 μg/kg b.w.) spleen damages and decreased the expressions of OTA-promoted apoptosis-related protein and pro-inflammatory cytokine. Further study indicated that APS caused significant enhancement of AMPK/SIRT-1 and inhibition of NFκB in PAMs and mice. The down-regulation of SIRT-1 by EX527 in vivo or EX527 and SIRT-1 knockdown in vitro abolished the inhibitory effects of APS on OTA-induced cytotoxicity, apoptosis, spleen damages and pro-inflammatory cytokine expressions. Taken together, these findings indicate that APS could attenuate the immune stress induced by OTA in vitro and in vivo via activation of the AMPK/SIRT-1 signaling pathway.

Keywords: AMPK; Astragalus polysaccharide; Immune stress; Ochratoxin A; SIRT-1.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / immunology
  • Animals
  • Astragalus Plant / chemistry*
  • Cell Line
  • Gene Expression Regulation / drug effects*
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / pharmacology*
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Ochratoxins / antagonists & inhibitors*
  • Ochratoxins / toxicity
  • Plant Extracts / chemistry
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Protective Agents / isolation & purification
  • Protective Agents / pharmacology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / genetics
  • Sirtuin 1 / immunology
  • Spleen / drug effects*
  • Spleen / immunology
  • Swine

Substances

  • Immunologic Factors
  • NF-kappa B
  • Ochratoxins
  • Plant Extracts
  • Polysaccharides
  • Protective Agents
  • RNA, Small Interfering
  • ochratoxin A
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1