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The current study aimed at investigating the therapeutic effects of rubusoside on type 2 diabetes mellitus (T2DM) mice models as an alternative hypoglycemic candidate drug. T2DM mice models were established with a combination of streptozotocin (STZ) intraperitoneal injection and high-fat diet. After 10 weeks of rubusoside intragastric administration (100, 200 mg/kg/day) to the mice, the body weight, fasting blood glucose, glucose tolerance, and blood lipids were measured. The liver protein expression levels of p-AMPK, GLUT2, GLUT4 and total antioxidant capacity were also investigated.    After 10 weeks of rubusoside administration, the levels of blood glucose and lipids were decreased in T2DM mice. Compared with the model group, rubusoside administration significantly decreased the liver mass-to-body weight ratio, upregulated p-AMPK and GLUT4, and downregulated GLUT2 expression levels in the liver. Activities of superoxide dismutase (SOD), catalase (CAT), and gluathione peroxidase (GSH-Px) were increased, and the concentration of malondialdehyde (MDA) was decreased to reduce oxidative stress in the liver. Liver hematoxylin and eosin (H&amp;E) pathological analysis also showed that rubusoside had a protective effect on T2DM mice liver.    These results demonstrate that rubusoside could be used as an anti-diabetic candidate drug, and that its hypoglycemic mechanism might be related to the activation of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) to modulate the expression of GLUT2 and GLUT4. Finally, rubusoside could also increase total antioxidant capacity to protect the liver from oxidative stress.

Rubusoside Reduces Blood Glucose and Inhibits Oxidative Stress by Activating the AMPK Signaling Pathway in Type 2 Diabetes Mellitus Mice