Screening Bioactive Compounds Of Jiegeng Decoction And Revealing Dynamic Behavior Of Target-components

Screening bioactive compound of traditional Chinese medicine（TCM）is a hot topic of innovative drugs development.Affinity chromatography is a powerful platform for screening the bioactive compounds of TCM.These methodologies come from the immobilized of target protein,and successfully applied in the aforementioned field.Recent advances in such methods are mostly focusing on the screening of bioactive compounds and the thermodynamic interaction between compound and target.The lack of dynamic investigation on target-compounds interaction has limited the broadly application.Jiegeng decoction is one of the classical recipe include in“shang-han lun”.In practice,the recipe is widely prescribed for fighting ailments of respiratory system including cough and asthma.The activity has indicated that there are certain compounds binding toβ₂-AR,the representative target mediating the diseases.Taking Jiegeng decoction as a probe,this thesis intends to perform a series of work on the screening of bioactive compounds targetingβ₂-AR,and reveal the dynamic interaction between the compounds andβ₂-AR.The dissertation was divided into three chapters among which the author contributed greatly in following contents:1.Coupled with ion trap mass spectrometry,the bioactive compounds specifically binding to the immobilizedβ₂-AR were screened and identified from Jiegeng decoction.The result illustrated that Playcodon D and Liquirtin apioside（or Isoliquiritin apioside）were the bioactive compounds targetingβ₂-AR for fighting cough and asthma from Jiegeng decoction.The established method preserves a great potential in screening bioactive compounds from complex systems based on the TCMs.2.Taking salbutamol sulfate,terbutaline sulfate,methoxynamine,isoprenaline hydrochloride,ephedrine hydrochloride as probes,two methods（Peak Profiling and Non-linear chromatography）were applied to evaluate the dynamic behaviors of the ligands binding to receptor.Meanwhile,the dissociation rate constant of Playcodon D was calculated by the two methods with the result of 3.70 s^-1and 0.50 s^-1,indicating that Playcodon D and other bioactive compounds have druggability in treating ailments of respiratory system.It provides a new idea for researching pharmacokinetics and screening other bioactive compounds in TCMs.