Anti-diabetic effects of Grifola frondosa bioactive compound and its related molecular signaling pathways in palmitate-induced C2C12 cells

Abstract

Ethnopharmacological relevance: Grifola frondosa (GF), a high value medicinal mushroom, is popularly consumed as traditional medicines and health foods in China and Japan. It is a herbal medicine traditionally used for treating inflammation, cancer and diabetes.

Aim of the study: This study aimed to examine the anti-diabetic effects of a GF bioactive compound ergosterol peroxide (EPO), and its mechanism(s) of action in palmitate (PA)-induced C2C12 cells.

Materials and methods: EPO was isolated and purified from GF fruiting bodies, and used to test for anti-diabetic activity in PA-induced murine C2C12 skeletal muscle cells through measuring glucose uptake, intracellular ROS production, and expressions of MAPKs, IRS-1, PI3K, Akt and GLUT-4 proteins.

Results: EPO significantly up-regulated glucose absorption and increased cell growth. At 5 μM, EPO significantly enhanced glucose uptake and decreased ROS formation, as well as up-regulated the expression of IRS-1, p-IRS-1, PI3K, Akt, p-Akt, and GLUT-4 proteins in PA-induced cells, while their p-JNK and p-p38 expression were down-regulated. GLUT-4 siRNA treatment effectively down-regulated the EPO-induced absorption of glucose and inhibited the expression of GLUT-4.

Conclusion: These results suggest that the anti-diabetic effect of GF was from its bioactive compound EPO through the inhibition of ROS production, up-regulation of glucose absorption, and modulation of PI3K/Akt, MAPKs and GLUT-4 signaling transduction pathways.

Keywords: Akt; C2C12 cells; Ergosterol peroxide; GLUT-4; MAPKs; PI3K.