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

Shih-Yu Lee,Jung-Chun Lin,Wen-Liang Chang,Su-Feng Huang,Blerina Ahmetaj-Shala,Wei-Cheng Tsai,Tsu-Chung Chang

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.

Highlights

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder, which can manifest as ulcerative colitis and Crohn’s disease[1]
We examined the effects of Astragaloside II (AS II), one of the major bioactive components of A. membranaceus, on repair and restoration of intestinal epithelial barrier function, and investigated the signaling mechanism involved
We found that AS II can promote scratch wound closure, cell proliferation, and arginine uptake, and can induce the arginine transporters CAT1 and CAT2 in differentiated human intestinal Caco-2 cells

Summary

Introduction

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder, which can manifest as ulcerative colitis and Crohn’s disease[1]. L-Arg increases intestinal protein synthesis and epithelial repair by activating the mechanistic target of rapamycin (mTOR) signaling pathway[14]. L-Arg contributes to wound healing and protein synthesis, while significantly enhancing mTOR signaling; this pathway may be a promising agent in intestinal wound closure. AS II increases L-Arg uptake and CAT protein levels in Caco-2 cells.

Results

Conclusion