针对穿心莲水煎液极苦特征的联合抑苦策略及抑苦机制研究  

Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism

作　　者：张前会 田寅 仇敏 韩雪 马鸿雁[1] 韩丽[1] 张定堃[1] ZHANG Qian-hui;TIAN Yin;QIU Min;HAN Xue;MA Hong-yan;HAN Li;ZHANG Ding-kun(State Key Laboratory of Southwestern Chinese Medicine Resources,Pharmacy School,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;School of Pharmacy,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都中医药大学药学院西南特色中药资源国家重点实验室,四川成都611137 [2]成都医学院药学院,四川成都610500

出　　处：《中国中药杂志》2022年第20期5424-5433,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81803745,82173991);四川省科技厅杰出青年人才项目(2019JDJQ0007);2019—2021年度中华中医药学会青年人才托举工程项目(2019-QNRC2-B05)。

摘　　要：考察两亲性聚合物、环糊精、甜味剂对穿心莲水煎液极苦特征的抑苦效果,筛选最佳联合抑苦配方;采用虚拟筛选与实验验证探究不同辅料抑苦的制剂学原理,阐明联合抑苦的协同作用。结果表明,mPEG_(2000)-PLLA_(2000)、γ-环糊精(γ-cyclodextrin,γ-CD)与阿斯巴甜对穿心莲水煎液均具有较好的抑苦作用,联合使用0.15%mPEG_(2000)-PLLA_(2000)、1.60%γ-CD与0.04%阿斯巴甜时,抑苦效果更佳,水煎液苦味值从8分(苦味严重)降至1分(几乎无苦味)。量子化学计算发现,mPEG_(2000)-PLLA_(2000)可降低苦味基团的静电势,自发与其结合并形成物理屏障,阻碍苦味成分与受体的结合。研究γ-CD与苦味成分的相互作用,发现γ-CD表面积和自由能减小,偶极矩增大,γ-CD可包合苦味成分并自组装形成超分子。分子对接发现,穿心莲内酯14位上羟基、16位上羰基与脱水穿心莲内酯3、4位上羟基、14位上羰基和五元内酯环可能是主要的苦味基团;阿斯巴甜与苦味受体TAS2R10、TAS2R14、TAS2R46结合自由能分别为-3.21、-1.55、-2.52 kcal·mol^(-1),阿斯巴甜可竞争抑制苦味基团与苦味受体结合。含量测定结果发现,穿心莲水煎液中穿心莲内酯、脱水穿心莲内酯游离量分别为0.23%、0.28%,加入掩味辅料后,水煎液中两者游离量分别降低至0.13%、0.20%。上述研究表明,mPEG_(2000)-PLLA_(2000)可通过胶束自组装,将部分苦味成分卷入其中,调和入口苦味;γ-CD可包合真溶液中剩余苦味成分,改善主体苦味;阿斯巴甜进一步竞争抑制苦味成分与苦味受体的结合,矫味增甜。多辅料联合抑苦策略可显著降低穿心莲苦味,全方位调控优化汤剂口感。Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction,and the optimal combined anti-bitterness formula was obtained.The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect.Sensory evaluation showed that mPEG_(2000)-PLLA_(2000),γ-cyclodextrin(γ-CD),and aspartame all had good anti-bitterness effect,which reduced the bitterness intensity of Andrographis Herba decoction by 0.5,6,and 3 points,respectively.The anti-bitterness effect was superior when 0.15%mPEG_(2000)-PLLA_(2000),1.60%γ-CD,and 0.04%aspartame were combined,and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness)to 1 point(almost no bitterness).Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups,which spontaneously combined with it and formed a physical barrier,hindering the binding of bitter components to receptors.The interaction betweenγ-CD and bitter components was studied.It was found that the surface area and free energy ofγ-CD decreased and the dipole moment increased,indicating thatγ-CD included bitter components and self-assembled to form supramolecules.Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide,and hydroxy at position 3 and 4,carbonyl at position 14,and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups.The binding free energies of aspartame to bitter receptors TAS2 R10,TAS2 R14,and TAS2 R46 were-3.21,-1.55,and-2.52 kcal·mol^(-1),respectively,indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors.The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction

关 键 词：穿心莲 苦味 掩味 中药汤剂伴侣 

分 类 号：R283.6[医药卫生—中药学]