Icariin reduces high glucose-induced endothelial progenitor cell dysfunction via inhibiting the p38/CREB pathway and activating the Akt/eNOS/NO pathway

High glucose (HG) impairs endothelial progenitor cell (EPC) function. The activation of p38 mitogen-activated protein kinase and the inhibition of the Akt/eNOS/NO pathway serve central roles in this process. Icariin has protective effects in endothelial cells. The aim of the present study was to investigate the effects of icariin on HG-induced EPC dysfunction, including proliferation, migration and tube formation. Experiments were performed with EPCs isolated from the femurs and tibias of Sprague-Dawley rats in vitro. In a dose-dependent manner, icariin reversed the inhibition of EPC proliferation induced by HG treatment, and the maximal effective concentration of icariin was 1 µM [Fold change (FC):0.90±0.07, P=0.0124 vs. HG group]. The impaired EPC migration and tube formation induced by glucose was partially restored by 1 µM icariin treatment (FC: 0.81±0.08, P=0.0148 vs. HG group for migration; 0.82±0.03, P=0.0214 vs. HG group for tube formation). Furthermore, icariin significantly suppressed HG-induced p38 and cAMP response element binding protein (CREB) phosphorylation in EPCs (FC: 1.84±0.21, P=0.0238 vs. HG group for p38; FC: 2.24±0.15, P=0.0068 vs. HG group for CREB). Increased Akt and endothelial nitric oxide (NO) synthase (eNOS) activation was also observed after icariin treatment (FC: 0.64±0.08, P=0.0047 vs. HG group for Akt; FC:0.53±0.05, P=0.0019 vs. HG group for eNOS), which was followed by increased NO production (FC: 0.69±0.06, P=0.0064 vs. HG group). In conclusion, icariin attenuated HG-induced EPC dysfunction, which may be partially attributed to the inhibition of the p38/CREB pathway and the activation of the Akt/eNOS/NO pathway. Icariin may be a therapeutic candidate for improving the function of EPC.