(P03-044-23) Structural Effects of Black Raspberry Seed Ellagitannins on Stimulation of Glucagon-Like Peptide-1 and Intestinal Bitter Taste Receptors in Mouse Enteroendocrine Cells

Objectives: Bitter flavor compounds, including ellagitannins, can bind to bitter taste receptors (TAS2R) due to their structures. Enterohormone secretion has been known to be regulated via intestinal TAS2R signaling pathway, contributing to healthy gut. The aim of this study was to investigate the structural effects of black raspberry seed (BS) ellagitannins on the stimulation of glucagon-like peptide-1 (GLP-1) secretion and mouse TAS2R (mTAS2R) gene expression in vitro.

Methods: Ellagitannin fraction from BS (BSEF) was prepared by open-column chromatography. STC-1 cells were treated with BSEF, BS ellagitannins (sanguiin H-6, casuarictin, pedunculagin, acutissimin A, castalagin, and vescalagin), and ellagitannin metabolites (ellagic acid and urolithin A) for 2 h. Denatonium benzoate (DB), known as a TAS2R agonist, was used as a positive control. Total GLP-1 level was measured by ELISA. mTas2r108, 119, 126, 131, 138, and 140 expressions were investigated by RT-qPCR after 3 h incubation with the ellagitannins (1 µM).

Results: Monomeric and dimeric ellagitannins were detected to be predominant in the BS. The BSEF treatment induced more GLP-1 secretion than the control. In addition, the BS ellagitannins even at a lower concentration (1 µM) stimulated GLP-1 secretion compared to DB. However, ellagic acid and urolithin A at up to 10 μM did not induce the GLP-1 secretion. All six BS ellagitannins upregulated mTas2r108, 119, 126, and 138 expressions. Sanguiin H-6 upregulated mTas2r140 expression the most among the tested mTas2r. Pedunculagin upregulated mTas2r131 expression the most among the six mTas2r, while casuarictin did not impact on the mTas2r131 expression. Acutissimin A, a flavano-ellagitannin in BS, more upregulated mTas2r108 expression than the other ellagitannins.

Conclusions: This study is the first to biologically demonstrate the stimulatory effects of BS ellagitannins on GLP-1 secretion and mTAS2R expressions, which could provide the potential applicability of BS ellagitannins in functional foods for improving gut health.

Funding Sources: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) and partially supported by BK21 FOUR Project of the NRF of Korea Grant.