Resveratrol regulates intestinal barrier function in cyclophosphamide-induced immunosuppressed mice

J Sci Food Agric. 2022 Feb;102(3):1205-1215. doi: 10.1002/jsfa.11458. Epub 2021 Aug 13.

Abstract

Background: Resveratrol, a kind of polyphenolic phytoalexin, can be obtained from numerous natural foods. Although resveratrol is demonstrated to have various bioactivities, little is known about the regulation of intestinal barrier function under immunosuppression. The present study is aimed at investigating the regulatory effect of resveratrol on intestinal barrier function in immunosuppression in mice induced by cyclophosphamide.

Results: The effects of resveratrol on intestinal biological barrier were evaluated by 16S rRNA and metagenome sequencing analysis. The results showed that resveratrol could improve diversity of the intestinal microbiota and intestinal flora structure by increasing the abundance of probiotics, and resveratrol regulated the function of gut microbiota to resist immunosuppression. Resveratrol could significantly upregulate the secretion of secretory immunoglobulin A and promote the transcriptional levels of test cytokines, including tumor necrosis factor α, interferon γ, interleukin 4 and interleukin 6 in jejunum and ileum mucosa, suggesting improved intestinal immune barrier by resveratrol. The mRNA and protein levels of tight junction proteins involved in intestinal physical barrier function, including zonula occludens 1 (ZO-1), claudin 1 and occludin, were increased after resveratrol treatment. The protein levels of toll-like receptor 4 (TLR4), phosphorylation nuclear factor kappa-B (NF-κB-p65) and inhibitor of nuclear factor kappa-B kinase α were decreased by resveratrol treatment when compared with the untreated group, indicating inhibition of the TLR4/NF-ĸB signaling pathway.

Conclusion: These results provide new insights into regulation of the intestinal barrier function by resveratrol under immunosuppression and potential applications of resveratrol in recovering intestinal function. © 2021 Society of Chemical Industry.

Keywords: cyclophosphamide; gut microbiota; immunosuppression; intestinal barrier function; resveratrol.

MeSH terms

  • Animals
  • Cyclophosphamide / adverse effects*
  • Gastrointestinal Microbiome / drug effects
  • Immunocompromised Host
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / genetics
  • Occludin / genetics
  • Occludin / immunology
  • Resveratrol / administration & dosage*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • NF-kappa B
  • Occludin
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma
  • Cyclophosphamide
  • Resveratrol