Molecular action mechanism of anti-inflammatory hydrolysates obtained from brewers' spent grain

J Sci Food Agric. 2020 May;100(7):2880-2888. doi: 10.1002/jsfa.10313. Epub 2020 Feb 21.

Abstract

Background: Brewers' spent grain (BSG) is a relevant, protein-rich by-product of the brewing process. Protein hydrolysates from different sources exert immune-regulatory actions activating toll-like receptors (TLRs), nuclear factor kappa B (NFκB), and mitogen-activated protein kinases (MAPKs). Effects of gastrointestinal digestion have been poorly studied. Here, we studied the immune-regulatory effect of BSG hydrolysates, and their in-vitro-digested products, on rat splenocytes, macrophages, and T lymphocytes RESULTS: In primary cultures of rat spleen cells, BSG hydrolysates induced interleukin 10 and tumor necrosis factor production in basal conditions. Under stimulation with lipopolysaccharide or concanavalin A, hydrolysates further induced interleukin 10 production. Tumor necrosis factor and interferon-γ were inhibited in lipopolysaccharide- and concanavalin-A-stimulated cells respectively. In vitro gastrointestinal digestion attenuated the observed effects. Splenic macrophages and T lymphocytes behaved in a similar fashion. In spleen cells from TLR2-/- and TLR4-/- mice, immune-regulatory effects were greatly reduced or abrogated. The study of signal transduction pathways indicated a major involvement of NFκB, and the contribution of MAPKs p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinases 1 and 2.

Conclusion: BSG hydrolysates, like those obtained from other food sources, regulate the immune response, involving TLR2 and TLR4 and the activation of NFκB and MAPKs, an effect partly maintained after in vitro gastrointestinal digestion. Our data support the hypothesis of a shared, rather unspecific, mechanism of action of protein hydrolysates. © 2020 Society of Chemical Industry.

Keywords: NFκB; TLR2; TLR4; brewing process by-product; immunomodulatory peptides; interleukin 10.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / metabolism*
  • Digestion
  • Edible Grain / chemistry*
  • Female
  • Immunologic Factors / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Plant Proteins / chemistry
  • Protein Hydrolysates / pharmacology*
  • Rats, Wistar
  • Spleen / drug effects
  • Spleen / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Toll-Like Receptors / metabolism

Substances

  • Cytokines
  • Immunologic Factors
  • NF-kappa B
  • Plant Proteins
  • Protein Hydrolysates
  • Toll-Like Receptors
  • Mitogen-Activated Protein Kinases