title: Hypoglycemic Activity and the Potential Mechanism of the Flavonoid Rich Extract from Sophora tonkinensis Gagnep. in KK-Ay Mice.
abstract: This study investigated the active principles, hypoglycemic activity and potential mechanisms of the flavonoid rich extract from Sophora tonkinensis Gagnep. (ST-EtOAc) in KK-Ay diabetic mice. An off-line semipreparative liquid chromatography-nuclear magnetic resonance (LC-NMR) and liquid chromatography-ultraviolet-electrospray ionization mass spectrometry (LC-UV-ESIMS) protocol was performed to determine 13 flavonoids from ST-EtOAc. ST-EtOAc administrated orally to the KK-Ay mice significantly increased their sensibility to insulin, reduced fasting blood-glucose levels and blood lipid indexes such as triglyceride and cholesterol. Moreover, ST-EtOAc exhibited a strong effect of stimulation on glucose transporter 4 (GLUT4) translocation by 2.7-fold in L6 cells. However, the selective AMP-activated protein kinase (AMPK) inhibitor compound C can completely inhibit the activation of the AMPK pathway and prevent the GLUT4 translocation caused by ST-EtOAc. In vivo, phosphorylation of the AMPK expression in the liver and skeletal muscle was measured. The results showed phosphorylation of the AMPK had been improved and GLUT4 expression had been also enhanced. In this paper, we conclude that, ST-EtOAc seems to have potential beneficial effects on the treatment of type 2 diabetes mellitus with the probable mechanism of stimulating GLUT4 translocation modulated by the AMPK pathway.
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Shihao
authors.initials: S
authors.lastname: Deng
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Han
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Sijian
authors.initials: S
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Ma
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for Nationalities Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, South-Central University for NationalitiesWuhan, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesShanghai, China; College of Biological Engineering, Tianjin University of Science and TechnologyTianjin, China.
authors.forename: Xinzhou
authors.initials: X
authors.lastname: Yang
keywords: GLUT4; KK-Ay mice; Sophora tonkinensis Gagnep.; hypoglycemic agents; p-AMPK