Icariin reduces Glu-induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH-SY5Y cells.

Excessive glutamate (Glu) can lead to significant effects on neural cells through the generation of neurotoxic or excitotoxic cascades. Icariin (ICA) is a main active ingredient of Chinese Medicine Berberidaceae epimedium L., and has many biological activities, such as antiinflammation, antioxidative stress, and anti-depression. This study aims to evaluate the effect of ICA on Glu-induced excitatory neurotoxicity of SH-SY5Y cells. The cell viability assay was evaluated by the CCK-8 assay. The apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were assessed by flow cytometry. Intracellular Ca2+ concentration was determined by using the fluorescent probe Fluo-3. Protein expression was detected by western blotting analysis. ICA can significantly enhance the SH-SY5Y cell viability reduced by Glu. At the same time, ICA can significantly reduce apoptosis, ROS, nitric oxide (NO) levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. In addition, ICA significantly increased the expression of P47phox and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active caspase-3, and active caspase-9. These results indicate that ICA may reduce the excitatory neurotoxicity of Glu-induced SH-SY5Y cells through suppression of oxidative stress and apoptotic pathways, suggesting that ICA could be a potential therapeutic candidate for neurological disorders propagated by Glu toxicity.