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

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.
Dandan Liu 1 Jiarui Su 1 Jiashan Lin 1 Gang Qian 1 Xingxiang Chen 1 Suquan Song 1 Kehe Huang 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
  • 2 College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China. Electronic address: khhuang@njau.edu.cn.
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.

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