Extrusion improved the anti-inflammatory effect of amaranth (Amaranthus hypochondriacus) hydrolysates in LPS-induced human THP-1 macrophage-like and mouse RAW 264.7 macrophages by preventing activation of NF-κB signaling

Mol Nutr Food Res. 2014 May;58(5):1028-41. doi: 10.1002/mnfr.201300764. Epub 2014 Jan 15.


Scope: The objective was to compare the anti-inflammatory potential of unprocessed and extruded amaranth pepsin/pancreatin hydrolysates in LPS-induced human THP-1 macrophages-like and mouse RAW 264.7 macrophages focusing on their anti-inflammatory mechanism of action related to NF-κB signaling pathway.

Methods and results: Amaranth hydrolysates were characterized by MS-MS and tested for anti-inflammatory effects on human and mouse macrophages. Peptides found in extruded amaranth hydrolysates displayed antioxidant capacity, angiotensin converting enzyme-inhibitor activity, and dipeptidyl peptidase-IV inhibitor activity. Gly-Pro-Arg peptide was present and reported as antithrombotic. Extruded amaranth hydrolysates (1 mg/mL) significantly reduced tumor necrosis factor alpha secretion in THP-1 and RAW 264.7 cells by 36.5 and 33.5%, respectively; with concomitant reduction in PGE2 (15.4 and 31.4%), and COX-2 (38.1 and 67.6%), respectively. Phosphorylation of IKK-α was significantly reduced by 52.5 and 88.2% leading to reduced phosphorylation of IκB-α (86.1 and 66.2%), respectively; resulting in a reduction in the expression of p65 NF-κB subunits in the nucleus by 64.2% for THP-1 and 70.7% for RAW 264.7 cells.

Conclusion: Amaranth hydrolysates inhibited LPS-induced inflammation in human and mouse macrophages by preventing activation of NF-κB signaling. Extrusion improved anti-inflammatory effect of amaranth hydrolysates in both cells, which might be attributed to the production of bioactive peptides during processing.

Keywords: Amaranthus hypochondriacus; Extrusion; Human THP-1 macrophages-like; Inflammation; Peptides.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amaranthus / chemistry*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Inflammation / drug therapy
  • Lipopolysaccharides
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Oligopeptides / pharmacology
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Signal Transduction*
  • Tandem Mass Spectrometry
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism


  • Anti-Inflammatory Agents
  • Antioxidants
  • I-kappa B Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Oligopeptides
  • Plant Extracts
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • glycyl-prolyl-arginine
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • I-kappa B Kinase