The present study aimed at identifying potential lead compounds for diabetes mellitus drug discovery. We developed a novel method involving centrifugal ultrafiltration separation subsequent liquid chromatography with ...The present study aimed at identifying potential lead compounds for diabetes mellitus drug discovery. We developed a novel method involving centrifugal ultrafiltration separation subsequent liquid chromatography with quadrupole time of flight tandem mass spectrometry （LC-Q/TOF-MS/MS） determination to screen a-glucosidase inhibitors in complex Scutellaria baicalensis Georgi （SBG） extract. By adding a second filter to the screening process, the level of non-specific binding of Compounds 1, 3, 10 and 11 was significantly decreased, and the level of non-specific binding of Compounds 5 and 15 also was reduced. As a result, five flavonoids identified as baicalein, baicalein, wogonin, chrysin, and oroxylin A, were rapidly found to interact with α-glucosidase and possess potent anti-a-glueosidase aetivity in vitro. Specific binding of ligands to a-glucosidase was demonstrated though the proposed method and the ligands could be ranked in order of affinity for α-glucosidase, which were corresponded to the order of inhibitory activity in vitro. In conclusion, our results indicated that the developed method is a rapid and effective screening method for rat intestinal α-glucosidase inhibitors from complex herbal medicines such as SBG.展开更多
基金supported by National Natural Science Foundation(No.88102881)the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.JKGQ201109)the Project Program of six talents peak,Jiangsu Province~~
基金supported by the National Key Scientific and Technological Special Projects(2012ZX09103-101-007)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT-IRT1193)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘The present study aimed at identifying potential lead compounds for diabetes mellitus drug discovery. We developed a novel method involving centrifugal ultrafiltration separation subsequent liquid chromatography with quadrupole time of flight tandem mass spectrometry （LC-Q/TOF-MS/MS） determination to screen a-glucosidase inhibitors in complex Scutellaria baicalensis Georgi （SBG） extract. By adding a second filter to the screening process, the level of non-specific binding of Compounds 1, 3, 10 and 11 was significantly decreased, and the level of non-specific binding of Compounds 5 and 15 also was reduced. As a result, five flavonoids identified as baicalein, baicalein, wogonin, chrysin, and oroxylin A, were rapidly found to interact with α-glucosidase and possess potent anti-a-glueosidase aetivity in vitro. Specific binding of ligands to a-glucosidase was demonstrated though the proposed method and the ligands could be ranked in order of affinity for α-glucosidase, which were corresponded to the order of inhibitory activity in vitro. In conclusion, our results indicated that the developed method is a rapid and effective screening method for rat intestinal α-glucosidase inhibitors from complex herbal medicines such as SBG.
