Antioxidant synergistic anti-inflammatory effect in the MAPK/NF-κB pathway of peptide KGEYNK (KK-6) from giant salamander (Andrias davidianus)

J Sci Food Agric. 2024 Nov;104(14):8613-8620. doi: 10.1002/jsfa.13689. Epub 2024 Jul 2.

Abstract

Background: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties.

Results: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1β (764.81 ng mL-1), interleukin-6 (1.06 ng mL-1) and tumor necrosis factor-α (4440.45 ng mL-1). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL-1; superoxide dismutase: 0.589 μg mL-1) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL-1).

Conclusion: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry.

Keywords: MAPK/NF‐κB pathway; antioxidant; anti‐inflammatory; peptide; synergy.

MeSH terms

  • Amphibian Proteins / chemistry
  • Amphibian Proteins / pharmacology
  • Animals
  • Anti-Inflammatory Agents* / chemistry
  • Anti-Inflammatory Agents* / pharmacology
  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • NF-kappa B* / genetics
  • NF-kappa B* / immunology
  • NF-kappa B* / metabolism
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Urodela*

Substances

  • Antioxidants
  • Anti-Inflammatory Agents
  • NF-kappa B
  • Peptides
  • Amphibian Proteins
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Superoxide Dismutase
  • Interleukin-1beta