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.

Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter

“…This screening system has been established according to our previous study [21,22]. To be brief, in cellular GLUTs storage vesicles (GSV), IRAP and GLUT4 displayed a strong co-localization reported by many researchers [23,24].…”

“…Protein extraction and western blotting analysis were performed according to our previous study [21,22]. Briefly, L6 cells were pre-incubated with different dosage of SMR (10, 20, 40 μg/mL) and insulin (10 nM) for 24 h before extracting proteins for western blot analysis.…”

“…FBG levels were measured every other week. Oral glucose tolerance test (OGTT) (2.0 g/kg glucose) was performed in overnight-fasted mice as described before [21,22]. The area under the curves (AUC) generated from the data collected during the OGTT was calculated.…”

“…Plasma insulin content was measured by using a rodent insulin enzyme-linked immunosorbent assay (ELISA) kit (Linco Research, St. Charles, MO). TC, TG, and FFA in liver and skeletal muscle were determined with corresponding assay kits (Jiancheng Bioengineering Institute, Nanjing, China) according to the method described previously [21,22]. Partial liver, pancreas, and WAT were fixed with 10% neutral-buffered formalin and embedded in paraffin; 3–4 μm thickness sections were taken with a tissue processor, and stained with HE solution for microscopy.…”

Bioinformatics: Inflammatory Cytokines and Attenuation of Diabetes Hypercholesterolemia-Induced Renal Injury Using Morning Glory and Necklace Pod Extracts

“…The chemical review on necklace pod ([NP], Sophora tomentosa, reveals the presence of alkaloids, polysaccharides, isoprenylated flavonoids, isoflavonones, flavones, flavonols, and their glycosides. Such compounds have been reported to have diverse bioactivities including antioxidant and immunoregulatory [6,8]. It was reported that the extracts of S. tonkinensis and Sophora flavescens significantly control the levels of insulin, through stimulation of glucose transporter 4 (GLUT-4) which is attenuated by AMP-activated protein kinase (AMPK) pathway while being non-toxic for mice [9].…”