目的 以2种不同的超分子,即黄芩苷-小檗碱(BA-BBR NG)和汉黄芩苷-小檗碱(WOG-BBR NF)为研究对象,利用弱键化学从"结构-构象-形态-活性"相关性探讨中药配伍"驱邪不伤正"的科学内涵。方法 基于2个超分子葡萄糖醛酸基团构象(A式和N式)的不同,结合2D-NMR分析和最低能量构象研究,采用激光扫描共聚焦显微镜(laser scanning confocal microscope,LSCM)、场发射扫描电子显微镜(field emission scanning electron microscope,FESEM)对超分子进行表征,从宏观和微观现象的不同探讨这种结构和构象的差异对超分子形态的影响;同时,通过微量肉汤稀释法、平板划线法、细菌形态观察及生物膜清除实验评价超分子活性的差异。结果 BA-BBR NG形态随浓度变化,当浓度大于成胶浓度(>10mmol/L),其形态在电镜中观察到球形超分子逐步形成"珍珠链"状超分子,而WOG-BBR NF在各浓度下均为非交联的刚性纳米纤维;BA、WOG的最优构型分别为N式和A式,但当它们各自和BBR通过弱键作用力自组装后,最优构型则转变成了A式和N式;另外,体外抑菌研究表明2个超分子对大肠杆菌、金黄色葡萄球菌和屎肠球菌的抑制作用与小檗碱相比明显不同,且超分子抑菌活性呈现"选择性"。结论 中药超分子物质基础与单体成分相比具有独特性,单体成分结构和构象的不同,会导致分子间相互作用在弱键诱导下形成不同的超分子形态,进而影响生物活性。

Objective In this paper, two different supramolecules, baicalin-berberine (BA-BBR NG) and wogonoside-berberine (WOG-BBR NF), were studied on the basis of previous studies. The scientific connotation of the compatibility of traditional Chinese medicine “expelling the pathogenic factor without harming the healthy qi” was discussed from the correlation of “structureconformation-morphology-activity” by weak bond chemistry. Methods Based on the different conformations of two supramolecular glucuronic acid groups (A form and N form), combined with 2D-NMR analysis and minimum energy conformation research, Laser scanning confocal microscope (LSCM) and Field emission scanning electron microscope (FESEM) were used to characterize the supramolecular. The effect of the difference of structure and conformation on the supramolecular morphology was discussed from the difference between macroscopic and microscopic phenomena. At the same time, the difference of supramolecular activity was evaluated by microbroth dilution method, plate marking method, bacterial morphology observation and biofilm scavenging experiment. Results The morphology of BA-BBR NG varies with the concentration. When the concentration was greater than the gel concentration (> 10 mmol/L), it was observed that the spherical supramolecules gradually form “pearl chain” supramolecules, while WOG-BBR NF was a non-crosslinked rigid nanofiber at all concentrations. The optimal configurations of BA and WOG were N form and A form, respectively, but when they self-assembled with BBR by weak bonding force, the optimal configurations were reversed. In addition, in vitro antibacterial studies showed that the inhibitory effects of the two supramolecules on Escherichia coli, Staphylococcus aureus and Enterococcus faecium were significantly different from those of berberine, and the supramolecular antibacterial activities were "selective". Conclusion Compared with monomer components, this study revealed the uniqueness of supramolecular material base of traditional Chinese medicine compatibility. The different structure and conformation of monomer components would lead to the formation of different supramolecular morphology induced by weak bonds, and then affected the biological activity.

R284

国家自然科学基金资助项目（82073974）；国家自然科学基金资助项目（82274072）；北京中医药大学重点攻关项目（2020-JYB-ZDGG-044）；北京市自然科学基金面上项目（7202116）；北京市科技新星计划（Z201100006820026）；中华中医药学会青年人才托举工程项目（CACM-2018-QNRC2-B08）；中央高校基金科研业务项目（2022-XJ-KYQD-008）；中央高校基金科研业务项目（BUCM-2019-JCRC002）；国家级高层次青年人才支持计划