Dendrobium huoshanense polysaccharides alleviate DSS-induced ulcerative colitis in mice: comparison between different parts of plant and role of GLP-1/GLP-1R axis.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium huoshanense has been long used to treat gastrointestinal disorders including ulcerative colitis (UC) in traditional Chinese medicine. Polysaccharides as its main active components can alleviate UC by reducing inflammation, and promote the secretion of glucagon-like peptide-1 (GLP-1), which possesses anti-inflammatory effects via GLP-1 receptor (GLP-1R). However, it remains unclear whether polysaccharides from different parts of this herb are equally effective in alleviating UC and whether polysaccharides function via GLP-1/GLP-1R axis. AIM OF THE STUDY: To identify the part in which the polysaccharide is most effective in alleviating UC and to explore its mechanism of action through GLP-1/GLP-1R axis. MATERIALS AND METHODS: The physicochemical properties of polysaccharides were analyzed. A dextran sulfate sodium (DSS)-induced UC mouse model was used to assess colitis-associated damage via morphological scoring, histopathological evaluation and inflammatory examination with multi-cytokine array and western blotting. Gut microbiota compositions, short-chain fatty acid contents and GLP-1 levels were measured, and their roles were checked using antibiotic mixture and GLP-1R antagonist Exendin (9-39). RESULTS: Stem, leaf and flower polysaccharides, with different molecular weight, monosaccharide composition and spatial conformation, differentially alleviated UC symptoms, and stem polysaccharide (DHPS) showed the strongest efficacy, as evidenced by improved epithelial integrity, mucus barrier and inflammatory disorder. DHPS-alleviated UC was independent of DHPS-altered gut microbiota and positively correlated with DHPS-elevated GLP-1 levels, which could be abolished by Exendin (9-39), suggesting that GLP-1-activated GLP-1R signaling mediated the effects of DHPS against UC. CONCLUSIONS: DHPS is the most effective polysaccharide for alleviating DSS-induced UC through GLP-1/GLP-1R axis, proposing DHPS is a valid candidate for UC treatment using D. huoshanense.