苦地丁消除细菌耐药性的活性成分及作用机制

In recent years, the problem of drug resistance of bacteria has been the grave concern of the international community and the medical profession and the traditional Chinese medicine must be come into notice because of its characteristics with multiple ways, levels and effect targets. On the basis of identification of the effective fraction of Corydalis Bengeana Tures for eliminating bacteria drug resistance and its mainly pharmacological activity, this project planned to separate the effective fraction by chromatographic separation strategy such as ODS and Sephadex. The alkaloids and flavonoids from the separation were prepared for systematic chemical separation. The chemical structure of monomeric compound from the separation was elucidated by the means of spectroscopy, assisted by the pharmacodynamical research to identify active constituent and effective components of Corydalis Bengeana Tures. And on this basis, we researched on how effective substance of effective fraction, active constituent and effective components affect the plasmids, biofilm formation and beta-lactamase of drug-resistance bacteria, investigated the relationship of effective fraction/active constituent/effective components, pharmacological activity and mechanism, elucidated each level of effective substance and mechanism of elimination bacteria drug resistance of Corydalis Bengeana Tures. This project would deepen the cognition of traditional effects scientific connotation, provide significant scientific basis for developing good curative effect, with independent intellectual property rights of the antagonist bacteria resistant new drugs, provide new ideas of researching other antimicrobial and anti-inflammation traditional Chinese medicine.

细菌耐药性是医药界面临的巨大的科学难题，而中药作为新的具有多途径、多层次、多靶点的特点备受瞩目。在已确定苦地丁消除细菌耐药性有效部位及其主要药理活性的基础上，本项目拟采用ODS及Sephadex等色谱分离策略对有效部位进行拆分，将拆分得到的生物碱类组分和黄酮类组分进行系统的化学分离，采用光谱学测试技术确定单体化合物的化学结构，并结合药效学研究确定苦地丁的有效组分和有效成分。在此基础上，研究有效部位、有效组分、有效成分三个层面的药效物质基础对耐药细菌的质粒、生物膜形成、主动外排泵系统、β-内酰胺酶的产生的变化，探讨有效部位/有效组分/有效成分?功效(药理作用)?作用机制的相关性，阐明苦地丁消除细菌耐药性的各层次药效物质基础及其作用机制。本项目可深化对苦地丁传统功效科学内涵的认识，为研制出疗效好、具有自主知识产权的拮抗细菌耐药性的新药提供重要科学依据，并可为其他抗菌消炎类中药提供新的思路。