Structure-activity relationship of coptis alkaloid bitterness inhibited by mPEG-PLLA

LI Pan1 QIU Min1 TIAN Yin1 KE Xiu-mei1 MA Hong-yan1 HAN Li1 YANG Ming2 ZHANG Ding-kun1

(1.State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China 611137)
(2.Key Laboratory of the Education Ministry for Modern TCM Preparation, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, China 330004)
【Knowledge Link】Homologous modeling

【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;


【Funds】 National Natural Science Foundation of China (81803745) 2019-2021 Youth Talent Support Project of China Association of Chinese Medicine (2019-QNRC2-B05) Outstanding Young Scientific and Technological Talent Project of Science & Technology Department of Sichuan Province (2019JDJQ0007)

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This Article


CN: 11-2272/R

Vol 45, No. 13, Pages 3128-3135

July 2020


Article Outline



  • 1 Materials
  • 2 Methods and results
  • 3 Discussion
  • References