Salidroside from Rhodiola wallichiana var. cholaensis reverses insulin resistance and stimulates the GLP-1 secretion by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis.

Abstract

The present study was aimed to investigate the mechanisms of salidroside (SAL) from Rhodiola wallichiana var. cholaensis on hypoglycemic and oxidative stress responses. The palmitate (PA)-induced GLUTag cells model and the glucosamine-induced insulin resistance model in HepG2 cells were built. SAL led to the up-regulation of the serum glucagon-like peptide 1 (GLP-1) level by facilitating the SCFAs production, the promotion of GLP-1 synthesis by improving p38 MAPK phosphorylation and regulating insulin resistance. Moreover, the production of reactive oxygen species (ROS) and the expression of MAPKs were down-regulated. Furthermore, SAL was found to be able to inhibit PA-induced apoptosis that down-regulates cleaved caspase-3 and Bax expressions, while up-regulating Bcl-2 expression and up-regulates the Bcl-2/Bax ratio in glucosamine induced insulin resistance model. Besides, SAL can also up-regulate the mTOR/p70S6k signaling pathway in the PA-induced GLUTag cells model. Our data demonstrated that SAL could reverse insulin resistance and stimulates the GLP-1 secretion by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. PRACTICAL APPLICATIONS: Our data showed that SAL could increase the GLP-1 level by stimulating the SCFAs production and p38 phosphorylation and facilitate the IR and GLP-1 synthesis by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. Furthermore, the SAL has also stimulated the mTOR/p70S6k signaling pathway in PA-induced GLUTag cells model. The results provided a possibility to employ SAL for diabetes treatment.