Anti-inflammatory activities of black raspberry seed ellagitannins and their structural effects on the stimulation of glucagon-like peptide-1 secretion and intestinal bitter taste receptors.

This study aimed to investigate the anti-inflammatory effects of ellagitannins from black raspberry seeds (BS) in vivo and the structural effects of ellagitannins on glucagon-like peptide-1 (GLP-1) secretion and intestinal bitter taste receptor (TAS2R) stimulation. For animal study, BS ellagitannin fraction (BSEF) was orally administered to mice with colitis induced by dextran sulfate sodium (DSS). The BSEF supplementation alleviated colonic inflammation, regulated inflammation-related cytokine levels in the mice with colitis, and increased the total GLP-1 secretion and GLP-1 receptor mRNA level in the inflamed gut. It also augmented the colonic gene expressions of mouse TAS2R (mTAS2R) 108, 119, 126, 131, 138, and 140; meanwhile, only mTAS2R108 expression was downregulated by DSS treatment. Six BS ellagitannins (sanguiin H-6, casuarictin, pedunculagin, acutissimin A, castalagin, and vescalagin) induced GLP-1 secretion in STC-1 cells and upregulated mTAS2R108, 119, 126, and 138 gene expressions. The major ellagitannins in BS (sanguiin H-6, casuarictin, pedunculagin, and acutissimin A) upregulated the gene expressions of mTAS2R131 and/or 140 known to be specifically distributed in mouse colon. Through molecular docking with mTAS2R108, the hexahydroxydiphenoyl, flavan-3-ol, glucose, and nonahydroxytriphenoyl moieties of the six BS ellagitannins were predicted to be involved in interacting with the receptor. BS ellagitannins could be promising candidates for preventing colon inflammation, likely via GLP-1 secretion induced by intestine-specific TAS2Rs.