摘要
抑苦是提高中药汤剂服用顺应性与临床疗效的重要举措。针对中药汤剂苦味成分分散度大、多成分苦味叠加、瞬时刺激强的特点,课题组前期提出了利用两亲性物质在水溶液中的自组装特性,减少苦味成分在真溶液中的分配,实现中药汤剂抑苦的新策略,并发现其对多种结构的苦味化合物产生了程度不一的抑苦效果,这可能与底物结构存在一定的关系。因此,该文以单甲氧基聚乙二醇-聚乳酸(mPEG-PLLA)与黄连中5种苦味生物碱巴马汀、药根碱、小檗碱、表小檗碱及黄连碱的相互作用为研究对象,探寻底物结构对抑苦掩味效果的影响。以志愿者感官试验研究mPEG-PLLA对黄连水煎液及其主要苦味生物碱的掩味效果,利用分子对接与分子力场定位苦味基团与掩味部位,通过苦味生物碱的表面静电势分析苦味强度与结构的关系,采用因子分析探究掩味效果与苦味成分结构参数的相关性,阐明mPEG-PLLA掩蔽黄连生物碱苦味的构-效关系。结果发现mPEG-PLLA对黄连水煎液与5种生物碱均具有显著的掩味效果,掩味效果与不同生物碱的结构明显相关:掩味效果随着苦味成分供氢体、可旋转键的数目增多而增大,相对分子质量、疏水性的增大而加强,表面静电势正值、亲电性、与苦味受体的结合能的增强而降低。该研究初步阐明了黄连苦味生物碱结构对mPEG-PLLA抑苦效果的影响,为更好地发挥两亲性嵌段聚合物的抑苦作用提供了科学依据。
Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM)decoction.According to the characteristics of TCM decoction,such as high dispersion of bitterness 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 bitterness 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 speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure.In this paper,the interaction between mPEG-PLLA and five bitter alkaloids(bamatine,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 the decoction of Coptidis Rhizoma 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 the decoction of Coptidis Rhizoma and 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 butter-masking effect of mPEG-PLLA was preliminarily elucidated,providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.
作者
李潘
仇敏
田寅
柯秀梅
马鸿雁
韩丽
杨明
张定堃
LI Pan;QIU Min;TIAN Yin;KE Xiu-mei;MA Hong-yan;HAN Li;YANG Ming;ZHANG Ding-kun(State Key Laboratory of Traditional Chinese Medicine Resources with Southwest Characteristics,Pharmacy College,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;State Key Laboratory of Modern Chinese Medicine Preparation Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2020年第13期3128-3135,共8页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(81803745)
2019—2021年度中华中医药学会青年人才托举工程项目(2019-QNRC2-B05)
四川省科技厅青年杰出科技人才项目(2019JDJQ0007)。
关键词
mPEG-PLLA
共聚物胶束
抑苦
黄连
静电势
结构参数
mPEG-PLLA
copolymer micelles
bitter-masking
Coptidis Rhizoma
electrostatic potential
structural parameters
