Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons

Capsaicin and resveratrol as natural products have a variety of beneficial effects. However, capsaicin is also a neurotoxic agent, rendering its effect on the nervous system confusing. The aim of this study was to investigate whether capsaicin and/or resveratrol have a protective effect against glutamate (Glu)-induced neurotoxicity. After exposure to glutamate for 15 min, cerebral cortical neurons of ICR mouse fetuses on embryonic days 15–16 were post-treated with capsaicin and/or resveratrol for 24 h. Glu induced a significant reduction in cell viability, but the cell viability increased significantly with capsaicin or resveratrol treatment and further was highest in the neurons co-treated with both phytochemicals. Glu-induced reactive oxygen species generation and apoptotic neuronal death also significantly decreased by a combined treatment with both phytochemicals. Due to Glu insults, the reduced mRNA levels of cytoplasmic glutathione peroxidase, copper/zinc and manganese superoxide dismutases, and Bcl-xL and the overexpressed mRNA levels of interleukin-1β and tumor necrosis factor-α were significantly restored by post-treatment of capsaicin and/or resveratrol. These findings indicate that capsaicin and resveratrol are neuroprotective against Glu-induced toxicity and that the combined treatment of both phytochemicals can enhance the neuroprotection, suggesting a useful therapeutic application in the treatment of neurodegenerative disorders.