Rhamnogalacturonan, a chemically-defined polysaccharide, improves intestinal barrier function in DSS-induced colitis in mice and human Caco-2 cells

Daniele Maria-Ferreira,Karla Carolina Paiva Bocate,Adamara Machado Nascimento,Fernando Bittencourt Luciano,René M Van Den Wijngaard,Debora De Mello Gonçales Sant´Ana,Paulo Da Silva Watanabe,Thales Ricardo Cipriani,Maria Fernanda De Paula Werner,Arquimedes Paixão Santana-Filho,Cristiane Hatsuko Baggio

doi:10.1038/s41598-018-30526-2

Abstract

Natural polysaccharides have emerged as an important class of bioactive compounds due their beneficial biological effects. Here we investigated the protective and healing effects of rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen leaves in an experimental model of intestinal inflammation in mice and in heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2). The findings demonstrated that RGal treatment for 7 days reduced the severity of DSS-induced colitis by protecting mice from weight loss, macroscopic damage and reduction of colon length. When compared to the DSS group, RGal also protected the colon epithelium and promoted the maintenance of mucosal enterocytes and mucus secreting goblet cells, in addition to conserving collagen homeostasis and increasing cell proliferation. In an in vitro barrier function assay, RGal reduced the cellular permeability after exposure to IL-1β, while decreasing IL-8 secretion and claudin-1 expression and preserving the distribution of occludin. Furthermore, we also observed that RGal accelerated the wound healing in Caco-2 epithelial cell line. In conclusion, RGal ameliorates intestinal barrier function in vivo and in vitro and may represent an attractive and promising molecule for the therapeutic management of ulcerative colitis.

Highlights

Natural polysaccharides have emerged as an important class of bioactive compounds due their beneficial biological effects
The same holds for the DAI (Disease Activity Index), where the dextran sulfate sodium (DSS) group presented visible blood in the stool, as well as a colon length reduction (61%) when compared to the naïve control group (Fig. 1C,D)
We demonstrated the reduction of epithelial permeability and cytokine secretion as well as the maintenance of the tight junction integrity in Caco-2 cells

Summary

Introduction

Natural polysaccharides have emerged as an important class of bioactive compounds due their beneficial biological effects. We investigated the protective and healing effects of rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen leaves in an experimental model of intestinal inflammation in mice and in heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2). Our previous studies revealed that this polysaccharide protected the gastric mucosa against acute lesions induced by ethanol and promoted gastric ulcer healing in a chronic ulcer model induced by acetic acid in rats. These effects were due to the increase of cellular proliferation and gastric mucus content, associated with the reduction of inflammatory parameters and oxidative stress, without toxicological effects after sub chronic exposure[12]. To substantiate possible effects on barrier function, we employed in vitro assays using heterogeneous human epithelial colorectal adenocarcinoma (Caco-2) cells

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