Astringent Gallic Acid in Red Wine Regulates Mechanisms of Gastric Acid Secretion via Activation of Bitter Taste Sensing Receptor TAS2R4

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 Blaufrankisch 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.

Typical Umami Ligand-Induced Binding Interaction and Conformational Change of T1R1-VFT

“…Furthermore, there was no effect of the nonumami-tasting compounds (e.g., cyclamate, NaCl, sucrose, citric acid, and quinine sulfate) on the RFI of refolded T1R1-VFT (p > 0.05, Figure 1F). 34,35 Receptor protein T1R3-VFT expressed as inclusion bodies in an E. coli system displayed the active function and capable of binding ligands with a fluorescence quenching manner after solubilization and refolding, 13 which was quite similar to our results.…”

Fecal microbiota and metabolomics revealed the effect of long-term consumption of gallic acid on canine lipid metabolism and gut health

“…Gallic acid is an excellent astringent that exhibits anti-diarrheal effects ( Sterneder et al, 2021 ). We previously demonstrated that dietary supplementation with 0.05% GA reduced FS and exhibited antidiarrheal activity against environmental stress-induced diarrhea in puppies ( Yang et al, 2022 ).…”

Nahrungsinhaltsstoffe: Chemorezeptor-vermitteltes pharmakonutritives Potenzial

“…Wie eine Interventionsstudie belegt, kann Koffein die Freisetzung von Magensäure sowohl verzögern als auch stimulieren, je nachdem, ob der Muntermacher aus Kaffee Bitterrezeptoren im Mund oder im Magen aktiviert 4 . Auch Gallussäure, die Wein und Tee einen adstringierenden und leicht bitteren Geschmack verleiht, stimulierte zumindest in vitro in Interaktion mit einem Bitterrezeptor die Säuresekretion von Magenzellen 5 . Sind Bitterstoffe in den Magen gelangt, regen sie durch die vermehrte Magensäuresekretion die Motilität des Magens an, sodass die Ausscheidung der bitter schmeckenden, potenziell schädlichen Stoffe gefördert wird 4 .…”