Lariciresinol Displays Anti-Diabetic Activity through Inhibition of α-Glucosidase and Activation and Enhancement of Insulin Signaling.

ABSTRACT

SCOPE The aim of this study is to investigate the antidiabetic effect of lariciresinol (LSR) in C2C12 myotubes and streptozotocin (STZ)-induced diabetic mice. METHODS AND RESULTS: To investigate antidiabetic potential of LSR, α-glucosidase inhibitory assay, molecular docking, glucose uptake assay, western blot assay on antidiabetic biomarkers are performed. STZ-induced diabetic model is used for in vivo study by calculating oral glucose tolerance test, histochemical examination, and glycogen assay. LSR inhibits α-glucosidase activity with an IC50 value of 6.97 ± 0.37 µM and acts as a competitive inhibitor with an inhibitory constant (Ki) value of 0.046 µM. In C2C12 cells, LSR activates insulin signaling leading to glucose transporter 4 (GLUT4) translocation and augmented glucose uptake. Furthermore, in Streptozotocin (STZ)-treated diabetic mice, 3 weeks of oral LSR administration (10 mg kg-1 ) considerably decrease blood glucose levels, while increasing insulin levels in an oral glucose tolerance test, improve pancreatic islet size, increase GLUT4 expression, and significantly enhance insulin signaling in skeletal muscle. LSR treatment also activates glycogen synthase kinase 3ß (GSK-3ß) resulting in improved glycogen content. CONCLUSION: The findings indicate a potential usefulness for oral LSR in the management and prevention of diabetes by enhancing glucose homeostasis.