title: Determination of α-glucosidase inhibitors from Scutellaria baicalensis using liquid chromatography with quadrupole time of flight tandem mass spectrometry coupled with centrifugal ultrafiltration.
abstract: 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 α-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-α-glucosidase activity in vitro. Specific binding of ligands to α-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.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jun-Ran
authors.initials: JR
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jian-Guang
authors.initials: JG
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpu_lykong@126.com.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D005419:Flavonoids / Q000276:immunology / Q000302:isolation & purification; D065089:Glycoside Hydrolase Inhibitors / Q000276:immunology / Q000302:isolation & purification*; D007004:Hypoglycemic Agents / Q000276:immunology / Q000302:isolation & purification; D010936:Plant Extracts / Q000737:chemistry*; D051381:Rats; D031364:Scutellaria baicalensis; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D005419:Flavonoids; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; C499814:Scutellaria baicalensis extract
keywords: Centrifugal ultrafiltration; Flavonoids; LC-Q/TOF-MS/MS; Scutellaria baicalensis; α-Glucosidase inhibitors