Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons

Neurons are damaged following prolonged exposure to high concentrations of corticosterone, particularly during chronic inflammatory and immune diseases. One of the main mechanisms underlying neuronal injury is apoptosis. In the present study the neuroprotective effects of icariin, an active natural ingredient from the Chinese plant Epimedium sagittatum maxim against corticosterone-induced apoptosis were examined in primary cultured rat hippocampal neuronal cells. Pre-treatment of neuronal cells with icariin suppressed corticosterone-induced cytotoxicity in a dose-dependent manner. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling assay (TUNEL) labeling demonstrated that icariin significantly reduced TUNEL-positive cell numbers induced by exposure of cultured neurons to corticosterone. Moreover, icariin markedly inhibited corticosterone-induced mitochondrial dysfunction, including improved mitochondrial membrane potential and inhibition of caspase-3 activation. Using western blot analysis, corticosterone activated p38MAPK, extracellular regulated kinase 1/2(ERK1/2) ,and c-jun N-terminal protein kinase 1(JNK1) ,while icariin blocked p38 MAPK, but not JNK1 or ERK1/2. Pharmacological approaches showed that the activation of p38MAPK plays a critical role in corticosterone-induced mitochondrial dysfunction and apoptosis. Taken together, the present results suggest that the protective effects of icariin on apoptosis in hippocampal neuronal cells are potentially mediated through blockade of p38 MAPK phosphorylation.