[Flavor-masking technologies for complex bitter-pungent systems in traditional Chinese medicine: a case study of...

Wuzhuyu Decoction, a classical prescription recorded in the Treatise on Cold Damage Disorders(Shang Han Lun), exhibits poor compliance among pediatric patients due to its intense bitterness and pungency. There is an urgent need to screen suitable flavor-masking formulations and elucidate their underlying mechanisms. In this study, volunteer-based visual analog scale(VAS) scoring and functional near-infrared spectroscopy(fNIRS) were employed to evaluate different flavor-masking formulations for Wuzhuyu Decoction. The optimal formulation was identified as comprising 20 mg·mL~(-1) hydroxypropyl beta-cyclodextrin(HP-β-CD), 3 mg·mL~(-1) ι-carrageenan, 1.5 mg·mL~(-1) mogroside, and 0.015% peppermint oil. This formulation reduced the bitterness score of the decoction from 8.20(severely bitter) to 2.17(slightly bitter), and the pungency score from 5.40(distinctly pungent) to 1.64(mildly pungent), with improvement rates of 73.54% and 69.63%, respectively. The flavor-masking mechanisms were investigated using Fourier-transform infrared spectroscopy(FTIR), molecular docking, quantum chemical calculations, and lingual surface thermography. The results showed that HP-β-CD effectively reduced the free 6-gingerol content in the decoction, thereby mitigating pungent stimulation. Peppermint oil lowered the lingual surface temperature, thus weakening the burning sensation associated with pungency. Among four anionic polysaccharides(κ-carrageenan, ι-carrageenan, xanthan gum, and sodium carboxymethyl cellulose) at matched viscosity(5 581.13 ± 30.00) cp, only ι-carrageenan significantly reduced bitterness, lowering the bitterness score from 8.20 to 5.86. Quantum chemical analysis revealed that ι-carrageenan reduced the electron cloud density of the nitrogen atom in evodiamine via intermolecular electrostatic induction, thereby attenuating bitterness perception. Additionally, mogrosides contributed sweetness, helping to correct unpleasant tastes. Validation studies were performed using three classical bitter-pungent prescriptions(Huanglian Decoction, Banxia Xiexin Decoction, and Guizhi Shaoyao Zhimu Decoction) which demonstrated that the proposed formulation significantly improved their bitter-pungent sensory profiles. This study addressed the bitter-pungent taste characteristics of traditional Chinese medicine(TCM) decoctions by summarizing a scientific flavor-masking strategy, i.e., controlling pungency through encapsulation, suppressing bitterness via electrostatic induction, and compensating with sweeteners and aromatics. The findings advance flavor-masking techniques in TCM decoctions from empirical trial-and-error methods to evidence-based scientific approaches.