The Mechanism of Bitterness Suppression in Huanglian Jiedu Decoction

Abstract Background Bitterness is one of the main reasons that affect the clinical efficacy of traditional Chinese medicine (TCM). Preliminary research shows γ-cyclodextrin (γ-CD) and neotame can significantly improve the taste of TCM, while its mechanism still remains unknown. Huanglian jiedu decoction (HLJDD), as a typical representative of the bitter prescription of TCM, will be a breakthrough point to study the taste correcting strategy of TCM in this study. Methods Firstly, UPLC-MS/MS was used to identify the ingredients of HLJDT. Secondly, pharmacophore model of bitter taste receptors (BTR) Tas2r10, Tas2r14 and Tas2r46 was built by Discovery Studio 4.0 software. Thirdly, bitter taste compounds in HLJDD were identified by pharmacophore model. Finally, molecular modeling was used to explore how γ-CD and neotame make effect. Results We found γ-CD masked bitterness by preventing bitter components from contacting its receptor, or reducing the affinity between them. While components are extremely rigid such as coptisine, cannot complete self-assemble with γ-CD. Hence, inclusion (γ-CD) is difficult to achieve good effects for drugs containing those compounds such as Coptidis Rhizoma and Phellodendri Chinrnsis Cortex. However, neotame can strongly bind with those extremely bitter compounds such as coptisine and epiberberine in Coptidis Rhizoma and Phellodendri Chinrnsis Cortex, and thus can mask taste of them significantly. Conclusions The strategy achieves a significant bitter block effect from blocking the formation of the bitter signal to hindering its transmission after the formation of the signal, achieving a multilevel and significant taste effect. This article provides references for the research and development of flavoring companions for TCM, which will help improving the clinical efficacy of TCM.