Collagen peptides from Acaudina molpadioides prevent CCl4 -induced liver injury via Keap1/Nrf2-ARE, PI3K/AKT, and MAPKs pathways

J Food Sci. 2022 May;87(5):2185-2196. doi: 10.1111/1750-3841.16142. Epub 2022 Apr 2.

Abstract

Collagen peptide from Acaudina molpadioides (AMP) showed antioxidative activity in H2 O2 -induced RAW264.7 cells in our pervious study. In this study, it was observed that AMP could effectively improve the morphology and function of liver in CCl4 -induced mice. After 200 mg/kg AMP treatment, the content of MDA in liver decreased by 62.3%, and the level of antioxidant enzymes (SOD, GSH-Px, and CAT) increased by more than 65%. Western blot results disclosed that AMP (200 mg/kg) upregulated the Nrf2 level by 73.8% and downregulated Keap1 by 41.0% in CCl4 -induced mice liver. The levels of p-ERK, p-JNK, and p-p38 in 200 mg/kg AMP treatment groups decreased by 57.3%, 40.9%, and 40.6%, but the levels of p-PI3K and p-AKT increased by 162.6% and 60.3%, respectively. Furthermore, the trends of Nrf2, Keap1, p-ERK, p-JNK, p-p38, p-PI3K, and p-AKT levels in H2 O2 -induced RAW264.7 cells after AMP treatment were similar to the results in CCl4 -induced mice liver. These findings provided evidence that AMP exerted antioxidant activity via Keap1/Nrf2-ARE, PI3K/AKT, and MAPKs pathways in vivo and in vitro. Therefore, the collagen peptide from A. molpadioides might represent a novel functional food to prevent acute liver injury via attenuation of oxidative stress.

Keywords: Acaudina molpadioides; Keap1/Nrf2-ARE; PI3K/Akt; collagen peptides; liver injury.

MeSH terms

  • Adenosine Monophosphate / metabolism
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Chemical and Drug Induced Liver Injury, Chronic* / metabolism
  • Collagen / metabolism
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Liver / metabolism
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Peptides / metabolism
  • Peptides / pharmacology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sea Cucumbers* / chemistry
  • Signal Transduction

Substances

  • Antioxidants
  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Peptides
  • Adenosine Monophosphate
  • Collagen
  • Proto-Oncogene Proteins c-akt