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Modulation of HIF-1α/COX-2 pathway associated with attenuation of intestinal mucosa inflammatory damage by Acanthopanax senticosus polysaccharides in lipopolysaccharide-challenged piglets

  • Changyou Fan (a1), Jie Han (a1), Xianjun Liu (a1), Fei Zhang (a1), Yingshan Long (a1) and Qitao Xie (a1)...

Abstract

Intestinal barrier inflammatory damage is commonly accompanied by hypoxia. The hypothesis that dietary Acanthopanax senticosus polysaccharides (ASPS) might modulate HIF-1α signaling pathway and contribute to attenuate intestinal injury was tested in lipopolysaccharide (LPS)-challenged piglets. Thirty-six weaned pigs were randomly allocated to one of the following three groups: (1) basal diet+saline challenge; (2) basal diet+LPS challenge; (3) basal diet with 800 mg/kg ASPS+LPS challenge. LPS was injected at 15, 18 and 21 d, and intestinal sections were sampled following blood collection at 21 d of the trial. The results showed ASPS administration reversed (P<0.05) LPS-induced decrease in average daily feed intake and rise (P<0.05) of diarrhea incidence and index. Biochemical index reflecting gut barrier damage and function involving ileal pro-inflammatory cytokines (TNF-α and IL-1β) and enzymes activity (DAO and lactase), as well as circulatory D-xylose were normalized (P<0.05) in LPS-challenged piglets receiving ASPS. ASPS also ameliorated intestinal morphological deterioration of LPS-challenged piglets, proven by elevated ileal villus height (P<0.05) and improved appearance of epithelial villus and tight junction ultrastructure. Moreover, ASPS prevented LPS-induced amplification of inflammatory mediators, achieved by depressed mRNA abundance of TNF-α, iNOS, and concentration of IL-1β in ileum. Importantly, ileal protein expressions of HIF-1α, COX-2 and NFκB p65 were also suppressed with ASPS administration (P<0.05). Collectively, these results suggest that the improvement of mucosal inflammatory damage and diarrhea in immune stress piglets are possibly associated with a novel finding where HIF-1α/COX-2 pathway down-regulation involved in NFκB p65-inducible releasing of inflammatory cytokines by dietary ASPS.

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Corresponding author

*Corresponding author. Dr J. Han, email hanjie1130@163.com
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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