Astragaloside II promotes intestinal epithelial repair by enhancing L-arginine uptake and activating the mTOR pathway

Sci Rep. 2017 Sep 26;7(1):12302. doi: 10.1038/s41598-017-12435-y.

Abstract

Astragaloside II (AS II) extracted from Astragalus membranaceus has been reported to promote tissue wound repair. However, the effect of AS II on inflammatory bowel disease is unknown. We investigated the effects and mechanism of AS II on intestinal wound healing in both in vitro and in vivo models. Human intestinal Caco-2 cells were treated with multiple concentrations of AS II to assess cell proliferation, scratch wound closure, L-arginine uptake, cationic amino acid transporter activity, and activation of the mTOR signaling pathway. These effects were also measured in a mouse model of colitis. AS II promoted wound closure and increased cell proliferation, L-arginine uptake, CAT1 and CAT2 protein levels, total protein synthesis, and phosphorylation of mTOR, S6K, and 4E-BP1 in Caco-2 cells. These effects were suppressed by lysine or rapamycin treatment, suggesting that the enhanced arginine uptake mediates AS II-induced wound healing. Similar results were also observed in vivo. Our findings indicate that AS II can contribute to epithelial barrier repair following intestinal injury, and may offer a therapeutic avenue in treating irritable bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / metabolism
  • Caco-2 Cells
  • Cell Proliferation / drug effects
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / pathology
  • Crohn Disease / chemically induced
  • Crohn Disease / drug therapy*
  • Crohn Disease / pathology
  • Humans
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Saponins / pharmacology*
  • Saponins / therapeutic use
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome
  • Trinitrobenzenesulfonic Acid / toxicity
  • Wound Healing / drug effects*

Substances

  • Saponins
  • astragaloside II
  • Trinitrobenzenesulfonic Acid
  • Arginine
  • TOR Serine-Threonine Kinases