Anti-diabetic activity of extract from Morus nigra L. twigs through activation of AMPK/PKC pathway in mice

Morus nigra L. is a traditional ethnomedicinal plants, which is used for the treatment of atherosclerosis, diabetes, hyperlipidemia, and hypertension. The aim of this study was to investigate the antidiabetic activity and potential mechanisms of ethyl acetate extract of Morus nigra L. twigs (MNT-EA). In L6 cells, MNT-EA significantly upregulated glucose uptake, and promoted GLUT4 translocation and expression through AMPK and PKC signaling pathway. In vivo, diabetic mice treated with MNT-EA for 4 weeks improved hyperglycemia, lipid metabolism disorders and insulin resistance. According to histopathological examination, MNT-EA attenuated hepatic steatosis, adipocyte hypertrophy, and islet lesions in diabetic mice. In addition, MNT-EA upregulated p-AMPK, p-PKC, and GLUT4 expression in liver, adipose, and skeletal muscle tissues, thereby enhancing glucose uptake and improving diabetic symptoms. It is the first time to demonstrate that MNT-EA exerted anti-diabetic effects through activation of AMPK/PKC/GLUT4 signaling pathway, providing a basis for the development of new anti-diabetic drugs.