Eckol Alleviates Intestinal Dysfunction during Suckling-to-Weaning Transition via Modulation of PDX1 and HBEGF

Int J Mol Sci. 2020 Jul 3;21(13):4755. doi: 10.3390/ijms21134755.

Abstract

Maintaining intestinal health in livestock is critical during the weaning period. The precise mechanisms of intestinal dysfunction during this period are not fully understood, although these can be alleviated by phlorotannins, including eckol. This question was addressed by evaluating the changes in gene expression and intestinal function after eckol treatment during suckling-to-weaning transition. The biological roles of differentially expressed genes (DEGs) in intestinal development were investigated by assessing intestinal wound healing and barrier functions, as well as the associated signaling pathways and oxidative stress levels. We identified 890 DEGs in the intestine, whose expression was altered by eckol treatment, including pancreatic and duodenal homeobox (PDX)1, which directly regulate heparin-binding epidermal growth factor-like growth factor (HBEGF) expression in order to preserve intestinal barrier functions and promote wound healing through phosphoinositide 3-kinase (PI3K)/AKT and P38 signaling. Additionally, eckol alleviated H2O2-induced oxidative stress through PI3K/AKT, P38, and 5'-AMP-activated protein kinase (AMPK) signaling, improved growth, and reduced oxidative stress and intestinal permeability in pigs during the weaning period. Eckol modulates intestinal barrier functions, wound healing, and oxidative stress through PDX/HBEGF, and improves growth during the suckling-to-weaning transition. These findings suggest that eckol can be used as a feed supplement in order to preserve the intestinal functions in pigs and other livestock during this process.

Keywords: HBEGF; barrier function; eckol; ethanol extract of dried E. cava.

MeSH terms

  • Animals
  • Animals, Suckling
  • Cell Line
  • Dioxins / therapeutic use*
  • Gene Expression Regulation, Developmental / drug effects
  • Heparin-binding EGF-like Growth Factor / genetics
  • Heparin-binding EGF-like Growth Factor / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Intestinal Diseases / drug therapy*
  • Intestinal Diseases / genetics
  • Intestinal Diseases / metabolism*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / growth & development
  • MAP Kinase Signaling System / drug effects
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Sus scrofa
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Weaning
  • Wound Healing / drug effects

Substances

  • Dioxins
  • Heparin-binding EGF-like Growth Factor
  • Homeodomain Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • eckol