Epiberberine Improves Hyperglycemia and Ameliorates Insulin Sensitivity in Type 2 Diabetic Mice

ABSTRACT Aim Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterised by absolute or relative insufficiency of insulin secretion. The alkaloids from Rhizoma coptidis have potential hypoglycemic effects. Epiberberine (EPI), a protoberberine alkaloid extracted from Rhizome coptidis , has been found to regulate lipid metabolism. Our study aimed to investigate the antidiabetic effects of EPI on mice with T2DM, as well as its underlying mechanism. Methods The T2DM model in mice was established using a combination of high‐fat diet and streptozotocin. Animals were divided into the control, T2DM, EPI‐low dose (50 mg/kg EPI), EPI‐medium dose (100 mg/kg EPI), EPI‐high dose (200 mg/kg EPI) and metformin (MTF) (200 mg/kg MTF) groups. Body weight, water/food intake, serum lipids, blood glucose tolerance, insulin sensitivity, histopathological alterations, insulin signalling pathway and inflammation‐related pathways in each group were detected. Results EPI significantly reduced blood glucose levels and water/food intake in T2DM mice. EPI reduced the levels of total cholesterol, total triglyceride, low‐density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase, and elevated the levels of high‐density lipoprotein cholesterol in serum. EPI effectively improved oral glucose tolerance, alleviated hepatic insulin resistance, decreased glycosylated haemoglobin levels and increased liver glycogen content. EPI ameliorated the histopathological alterations of skeletal muscle and liver in T2DM mice. EPI stimulated the insulin signalling pathway by increasing glucose transporter type 4 levels and activating insulin receptor substrate‐1, phosphatidylinositol 3‐kinase and protein kinase B in skeletal muscle and liver. EPI reduced the levels of proinflammatory cytokine in serum and inhibited the activation of mitogen‐activated protein kinase signalling in skeletal muscle and liver of diabetic mice. Conclusion Overall, these data demonstrate that EPI alleviates the symptoms of T2DM, providing new insights into EPI as a therapeutic compound for the alleviation of T2DM.