A Digestive Herbal Mixture Preparation Stimulates Proton Secretion in Human Parietal Cells through Phenolic Compounds Targeting Bitter Taste Receptors

The effects of herbal remedies aiding digestion are well known, but the underlying mechanisms remain poorly understood. Notably, many of these preparations are bitter, and bitter‐tasting phenolic food constituents have been shown to induce digestive processes by activating extra‐oral bitter taste receptors (TAS2Rs). This study examined the effects of a commercially available herbal mixture preparation used to aid digestive discomfort and nine solvent extracts thereof on proton secretion of immortalized human parietal cells (HGT‐1). The bitter taste of the preparation was sensorially evaluated, and its impact on the gene expression of the polyphenol‐related receptors TAS2R4 , TAS2R5 , and TAS2R39 was analyzed. Functional TAS2R involvement was validated using CRISPR‐Cas9 knock‐out and siRNA knock‐down approaches. Total polyphenol content was quantified using Folin‐Ciocalteu reagent. The bitter‐tasting herbal mixture preparation and several of its solvent extracts stimulated proton secretion by HGT‐1 cells concentration‐dependently. Four extracts exhibited high total polyphenol content and induced strong secretory responses, whereas five extracts showed lower content and weaker effects ( p < 0.01). Reduced responses were observed in TAS2R4ko, TAS2R5kd, and TAS2R39ko cells. In conclusion, bitter‐tasting plant extracts can stimulate TAS2R‐mediated digestive processes depending on their total polyphenol content, thereby supporting their use as promising remedies for alleviating digestive discomfort.