Ginsenoside Rb1 stimulates adiponectin signaling in C2C12 muscle cells through up-regulation of AdipoR1 and AdipoR2 proteins

Abstract

Context: Rb1 ginsenoside, the key element of ginseng root, is widely used as an herbal therapeutic drug in diabetic patients. Various hypoglycemic mechanisms have been described for Rb1; however, to date, there has been no report on the effect of Rb1 on adiponectin signaling.Objectives: The current study was performed to establish the effects of ginsenoside Rb1 on the gene expression of AdipoR1 and AdipoR2 and their correlation to GLUT4 translocation in C2C12 myocytes.Materials and methods: C2C12 myotubes were incubated with various concentrations of Rb1 (0.001–100 µM) for different incubation times (1–12 h). Real time PCR and western blot analyses were performed to investigate the expression changes of adiponectin receptors (AdRs) and GLUT4 translocation, respectively. Gene silencing of AdipoR1 using specific siRNA was used to determine whether inhibition of AdipoR1 would reduce Rb1-induced GLUT-4 translocation in C2C12 cells.Results: Rb1 significantly stimulated basal AdRs expression levels in a time and dose-dependent manner; the maximal effect was attained at a concentration of 100 µM and a time of 3 h (p < 0.05). In muscle cells, Rb1 increased GLUT4 translocations to the cell surface, which was correlated with increasing the adiponectin receptors gene expression. Rb1-induced GLUT4 translocation was inhibited by the silencing of AdipoR1 mRNA.Discussion and conclusion: These results suggest that ginsenoside Rb1 promote translocations of GLUT4 by activating the adiponectin signaling pathway. The results can be helpful in understanding the novel antidiabetic mechanism of Rb1 ginsenoside and gain further support for its use as an antidiabetic drug.