Bitterness-Suppressing Effect of Umami Dipeptides and Their Constituent Amino Acids on Diphenhydramine: Evaluation by Gustatory Sensation and Taste Sensor Testing

Abstract

Diphenhydramine, a sedating antihistamine, is an agonist of human bitter taste receptor 14 (hTAS2R14). Diphenhydramine hydrochloride (DPH) was used as a model bitter medicine to evaluate whether the umami dipeptides (Glu-Glu and Asp-Asp) and their constituent amino acids (Glu, Asp) could suppress its bitterness intensity, as measured by human gustatory sensation testing and using the artificial taste sensor. Various concentrated (0.001-5.0 mM) Glu-Glu, Asp-Asp, Glu and Asp significantly suppressed the taste sensor output of 0.5 mM DPH solution in a dose-dependent manner. The effect of umami dipeptides and their constituent amino acids was tending to be ranked as follows, Asp-Asp > Glu-Glu >> Gly-Gly, and Asp > Glu >> Gly (control) respectively. Whereas human bitterness intensity of 0.5 mM DPH solution with various concentrated (0.5, 1.0, 1.5 mM) Glu-Glu, Asp-Asp, Glu and Asp all significantly reduced bitterness intensity of 0.5 mM DPH solution even though no statistical difference was observed among four substances. The taste sensor outputs and the human gustatory sensation test results showed a significant correlation. A surface plasmon resonance study using hTAS2R14 protein and these substances suggested that the affinity of Glu-Glu, Asp-Asp, Glu and Asp for hTAS2R14 protein was greater than that of Gly-Gly or Gly. The results of dockingsimulation studies involving DPH, Glu-Glu and Asp-Asp with hTAS2R14, suggested that DPH is able to bind to a space near the binding position of Glu-Glu and Asp-Asp. In conclusion, the umami dipeptides Glu-Glu and Asp-Asp, and their constituent amino acids, can all efficiently suppress the bitterness of DPH.

Low molecular weight peptides in tauco, a fermented soy product, associated to umami taste through peptidomics‐sensomics approach

“…In flavour aspects, the addition of sugar in the final product contributes to the pleasant flavour by balancing the sour taste produced during fermentation (Clemens et al ., 2016). The bitter taste was not recognised in all tauco fractions because the bitter taste could be suppressed by the presence of umami compounds as proven by a taste biology study (Okuno et al ., 2020). Apart from being the umami fractions, SUM and SIM fractions had a relatively high intensity of salty taste, at DF‐salty of 8 and 16, respectively.…”

Comparative Metabolomic Analysis of Moromi Fermented Using Different Aspergillus oryzae Strains

“…As for soy sauce, the direct contribution of peptides to its taste is negligible due to the relatively low content [ 31 ]. In addition, some amino acids (arginine, aspartic acid, and glutamic acid) and salt can act as bitterness suppressors [ 39 , 40 ].…”

Preparation and Characterization of Orally Fast-Disintegrating Mini-Tablets Containing Diphenhydramine Hydrochloride and Aspartic or Glutamic Acid as an Umami Amino Acid

“…In the present study, Asp and Glu were selected as bitterness suppressants; both amino acids are non-toxic and quite stable with bitterness-suppressing effects shown to be almost equivalent to those of L-aspartyl-L-aspartic acid and/or L-glutamyl-L-glutamic acid in our previous study [5].…”

“…Diphenhydramine hydrochloride (DPH) was chosen as a model drug as it is already widely used in pediatric and geriatric patients. This drug is known to have a bitter taste [5] so the addition of a bitterness suppressant is essential when the OFDMTs containing DPH are expected to disintegrate rapidly in the oral cavity, resulting in high concentrations of DPH being exposed to bitterness receptors on the tongue. Such a level of bitterness would greatly decrease adherence.…”