Antidiabetic Activity and Potential Mechanism of Amentoflavone in Diabetic Mice

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-06, Vol.24 (11), p.2184
• Main Authors: Su, Chengfu, Yang, Chuanbin, Gong, Man, Ke, Yingying, Yuan, Peipei, Wang, Xiaolan, Li, Min, Zheng, Xiaoke, Feng, Weisheng
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antidiabetics; Antioxidants; biochemical indexes; Cholesterol; Diabetes; Diabetes mellitus; Drug dosages; Fatty liver; Flavonoids; Glucagon; Glucokinase; Glucose; glucose metabolic enzyme; Glucose metabolism; Glucose transporter; Glucose-6-phosphatase; GLUT4 translocation; Glycogen; Glycogen synthase kinase 3; Glycogens; High density lipoprotein; High fat diet; Histopathology; Immunoreactivity; Insulin; Insulin resistance; Lipid metabolism; Lipids; Liver; Low density lipoprotein; Malondialdehyde; Metabolism; Muscles; Musculoskeletal system; Oxidants; Oxidizing agents; Pancreas; Phosphofructokinase; PI3K/Akt; Pyruvate kinase; Rodents; Skeletal muscle; Superoxide dismutase; Translocation; Triglycerides
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24112184

To investigate the anti-diabetic activity of amentoflavone (AME) in diabetic mice, and to explore the potential mechanisms. Diabetic mice induced by high fat diet and streptozotocin were administered with amentoflavone for 8 weeks. Biochemical indexes were tested to evaluate its anti-diabetic effect. Hepatic steatosis, the histopathology change of the pancreas was evaluated. The activity of glucose metabolic enzymes, the expression of Akt and pAkt, and the glucose transporter type 4 (GLUT4) immunoreactivity were detected. AME decreased the level of glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and glucagon, and increased the levels of high density lipoprotein cholesterol (HDL-C) and insulin. Additionally, AME increased the activity of glucokinase (GCK), phosphofructokinase-1 (PFK-1), and pyruvate kinase (PK), and inhibited the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Mechanistically, AME increased superoxide dismutase (SOD), decreased malondialdehyde (MDA), activation of several key signaling molecules including pAkt (Ser473), and increased the translocation to the sedimenting membranes of GLUT4 in skeletal muscle tissue. AME exerted anti-diabetic effects by regulating glucose and lipid metabolism, perhaps via anti-oxidant effects and activating the PI3K/Akt pathway. Our study provided novel insight into the role and underlying mechanisms of AME in diabetes.