Discovery of the relationship between bitter taste and bitter flavor (efficacy) based on hTAS2Rs

To explore the relationship between bitter taste and bitter flavor (efficacy), their characteristics were analyzed at the target and pharmacodynamic points. Compounds with bitter receptor activity were obtained by high-throughput screening models of the human bitter taste receptors (hTAS2Rs), which were used to analyze bitter taste. The efficacy of anti-asthma medications was used as an example to research bitter flavor (efficacy). The pharmacological effects of bitter taste and bitter flavor (efficacy) were classified according to the functional modules. The coverage for the same targets or pharmacological effects in the overall protein interaction network (PIN) of bitter taste and bitter flavor (efficacy) was analyzed to reveal their relationship. The effect of the compound polydatin with anti-asthma activation on hTAS2R14 was studied to verify the reliability of the aforementioned idea. A total of 121 Chinese materia medica (CMM) compounds that activate hTAS2R10, hTAS2R14, and hTAS2R49 were obtained. The analysis results indicated that 108 same targets for bitter taste and bitter flavor (efficacy) were obtained, accounting for 13.9% in the PIN of bitter taste and 72.5% in the PIN of bitter flavor (efficacy). The pharmacological effects shared by bitter taste and bitter flavor (efficacy) accounted for 79% of the PIN of bitter taste and 81% of the PIN of bitter flavor (efficacy). The activating effect of the anti-asthma compound polydatin on hTAS2R14 was dose-dependent with EC50 of 4.3 μM. In this study, the relationship between bitter taste and bitter flavor (efficacy) has been demonstrated from the target and pharmacodynamic points, which are based on hTAS2Rs and anti-asthma effect. Bitter taste and bitter flavor (efficacy) exhibited a high correlation. This study provides a theoretical and scientific basis for the hypothesis that "the property theory of CMM is the clinical pharmacodynamics of CMM."