A Rapid Method for the Identification and Screening of Bitter Compounds Using Moslae Herba as a Case Study

ABSTRACT

Moslae Herba, a commonly used traditional Chinese medicine with both diaphoretic and diuretic properties, exhibits intense bitterness in its clinical decoction, which severely compromises patient compliance. As a highly representative and typical case among bitter‐tasting Chinese medicinal materials, it serves as an ideal model drug for establishing a rapid screening strategy for bitter compounds, offering significant methodological demonstration value. This study establishes a rapid strategy for the identification and screening of bitter compounds using Ultra‐high performance liquid chromatography quadrupole‐time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) combined with pharmacophore modelling and molecular docking, and to apply this strategy to the screening of bitter compounds in the Moslae Herba decoction (MHD). Qualitative analysis of chemical constituents in MHD was performed using UPLC‐Q‐TOF‐MS combined with database searching, followed by construction of pharmacophore models based on high‐correlation bitter receptors from the BitterX database to screen potential bitter compounds. Molecular docking was subsequently employed to validate the screening results. Twenty‐one chemical constituents were identified in MHD, among which 15 potential bitter compounds—including astragalin, chrysoeriol, luteolin, and apigenin—were screened via pharmacophore modelling. Tas2r1, Tas2r14 and Tas2r39 identified 12, 14 and 5 candidate compounds, respectively. Molecular docking results were highly consistent with pharmacophore predictions, preliminarily confirming the strategy's reliability. This integrated approach enables rapid identification and screening of bitter constituents, successfully identifying 15 potential bitter compounds from MHD and providing a scientific basis for taste‐masking development and quality marker screening for Moslae Herba formulations. The strategy offers a methodological reference for efficient bitter‐compound discovery in traditional Chinese medicine and the food industry, with significant potential for broader application.