Structure-activity relationship of coptis alkaloid bitterness inhibited by mPEG-PLLA
(2.Key Laboratory of the Education Ministry for Modern TCM Preparation, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China 330004)
【Abstract】Inhibition of bitterness is a significant measure to improve patients’ compliance and the clinical efficacy of traditional Chinese medicine (TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitter components, multi-component bitterness superposition, and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitter components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was inferred that there might be a certain relationship between the bitterness inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids (palmatine, jatrorrhizine, berberine, epiberberine, and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on Coptidis Rhizoma decoction and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on Coptidis Rhizoma decoction and the five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity, and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the bitter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.
【Keywords】 mPEG-PLLA; copolymer micelles; bitter-masking; Coptidis Rhizoma; electrostatic potential; structural parameters;
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