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

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. [Display omitted] •Astragalus polysaccharide (APS) alleviates immune stress induced by ochratoxin A (OTA) in PAMs and mice.•APS activates Sirtuin 1 (SIRT-1) dependent of the AMPK phosphorylation.•SIRT-1 activation by APS inhibits the activity of NFκB by p65 deacetylation.•SIRT-1 inhibitor or SIRT-1-specific siRNA eliminates the APS-triggered protection against the immune stress of OTA.•SIRT-1 is required for APS to attenuate OTA-induced immune stress in vitro and in vivo.