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.