Insight into\nthe Interaction of <i>Humulus lupulus</i> L. Specialized\nMetabolites and Gastrointestinal Bitter Taste Receptors: <i>In\nVitro</i> Study in STC‑1 Cells and Molecular Docking

Bitter taste receptors, also known as taste 2 receptors\n(T2R),\nare expressed throughout the body and are involved in regulating different\nphysiological processes. T2R expression in the intestinal tract regulates\norexigenic and anorexigenic peptide secretion, thus becoming potential\na potential target for controlling food intake and the prevalence\nof obesity and overweight. The present study aims to investigate the\nimplication of hop bitter compounds such as α-acids, β-acids,\nand xanthohumol in the secretion of anorexigenic hormones and T2R\nexpression in intestinal STC-1 cells. The tested bitter compounds\ninduced the secretion of the anorexigenic hormones glucagon-like peptide\n1 and cholecystokinin concurrently with a selective increase of murine <i>Tas2r</i> expression. Xanthohumol and α-acids selectively\nincrease <i>Tas2r</i>138 and <i>Tas2r</i>130–<i>Tas2r</i>138 expression, respectively, in STC-1 cells, while\nβ-acids increased the expression of all bitter receptors studied,\nincluding <i>Tas2r</i>119, <i>Tas2r</i>105, <i>Tas2r</i>138, <i>Tas2r</i>120, and <i>Tas2r</i>130. Increased intracellular calcium levels confirmed this activity.\nAs all investigated bitter molecules increased <i>Tas2r</i>138 expression, computational studies were performed on <i>Tas2r</i>138 and its human orthologue T2R38 for the first time. Molecular\ndocking experiments showed that all molecules might be able to bind\nboth bitter receptors, providing an excellent basis for applying hop\nbitter molecules as lead compounds to further design gastrointestinal-permeable\nT2R agonists.