Abstract

Red wine is rich in phenolic compounds, which chiefly determine its characteristic taste. One of its major phenolic acid constituents for which an astringency, yet no clear contribution to bitter taste has been reported, is gallic acid (GA). In previous studies, we have demonstrated bitter-tasting constituents to regulate cellular proton secretion (PS) as a key mechanism of gastric acid secretion via activation of bitter taste sensing receptors (TAS2Rs). Here, we hypothesized a contributing role of GA to the red wine-stimulated effect on PS in human gastric tumor cells (HGT-1 cells). Sensory analyses revealed that 10 μM GA as the lowest concentration tested more bitter than tap water, with increasing bitter ratings up to 1000 μM. In HGT-1 cells, the concentration of 10 μM GA evoked the most pronounced effect on PS secretion, either when added to cells as in-water solution or when spiked to a red wine matrix. GA-spiking of Zweigelt and Blaufränkisch red wine samples up to a concentration of 10 μM resulted in an equally stimulated PS, whereas the non-GA-spiked wine samples demonstrated contrary effects on PS, indicating a functional role of GA on PS. Involvement of TAS2R4 in the GA-induced PS was verified by means of an HGT-1 homozygote CRISPR-Cas9 TAS2R4 knockout approach. Moreover, gene expression analyses revealed GA to increase TAS2R4. These results demonstrate a functional role of TAS2R4 in GA-evoked PS as a key mechanism of gastric acid secretion aiding digestion. Moreover, our data provide mechanistic insights, which will help to produce stomach-friendly red wines.

Highlights

  • Gallic acid (GA) is known to contribute to the astringent sensory quality of red wine.[1−3] This role of gallic acid (GA) was identified by combining sensory taste dilution approaches with instrumental analysis, thereby relying on sensory perception

  • Wine samples and GA in wine-representative concentrations alone with or without modulators were added to HGT-1 cells for up to 60 min in a Dulbecco’s modified Eagle’s medium (DMEM) dilution of 1:250, with the final, wine-representative ethanol concentration not exceeding 0.06%

  • Available data suggest astringency to be a trigeminal sensation that involves activation of G-protein-coupled signaling by phenolic compounds,[58] which might be reduced by interactions between the astringent molecules with saliva proteins.[6,59−64] Red wine constituents, for which an astringent sensation has been reported by Hufnagel and Hofmann, are hydroxybenzoic acids, bearing a catechol and/or galloyl group, such as protocatechuic acid, GA, and syringic acid.[3]

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Summary

Introduction

Gallic acid (GA) is known to contribute to the astringent sensory quality of red wine.[1−3] This role of GA was identified by combining sensory taste dilution approaches with instrumental analysis, thereby relying on sensory perception. The contribution of GA to the bitter perception of wine is less clear. Sensory perception analyses are not always sensitive enough to allow the identification of putative taste sensing chemoreceptor ligands, since dominant taste qualities might mask weaker ones. For GA, e.g., an astringent taste quality has been reported repeatedly,[2,3,12] whereas its contribution to the bitter taste of red wine is still not clear (Table S1)

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