Gleditsia Anti-myocardial Ischemia Active Ingredient Screening And Mechanism Study

Gleditsia sinensis Lam.was extensively used in the clinical practices of Traditional Chinese Medicine.Its anti-myocardial ischemia effects and the mechanisms were studied by the phytochemical, pharmacological and the molecular methods in the thesis,according to clinical experiences and the Tradional Chinese Medicial theories.The results showed as:Firstly,the Gleditschia saponin had the anti-myocardial ischemia effects,which was not as good as that of the Gleditschia sapogenin.The result suggested that the Gleditschia sapogenin was the mainly active fraction of the Gleditschia saponin in vivo,according to theories of intestinal flora metabolism and serum pharmacological study.Secondly,the Gleditschia sapogenin mainly include the echinocystic acid(EA) and the oleanolic acid(OA),both of which had the similar anti-myocardial ischemia activity.It was the first time that the EA and the OA were reported as the main components with anti-myocardial ischemia activity of Gleditsia sinensis Lam.Thirdly,a high performance liquid chromatographic method had been established to study the bioavailability of the EA.The quantitative limitation,linearity and repeatability of the method were satisfactory.Fourthly,the CaCo-2 cell model and the rat pharmacokinetic model were employed to compare the bioavailability of the EA and its sodium salt. The resuts revealed that the sodium salt of EA had the better bioavailability than EA.Fifthly,the anti-myocardial ischemia mechanisms of EA were investigated at the animal,cell,and gene levels respectively.The results showed that the mechanisms were related with improving resistance to anoxia,protecting myocardial cell,antioxygen activity and inhibiting myocardial apoptosis.To sum up,the study revealed the effects of Gleditsia sinensis Lam. on myocardial ischemia,also explored the bioavailability and mechanisms of the main active component(EA) of Gleditsia sinensis Lam.profoundly, which provided the experimental basis for the development and the clinlc use of Gleditsia sinensis Lam..