Protective effect of radicicol against LPS/IFN-γ-induced neuronal cell death in rat cortical neuron–glia cultures

Abstract

We investigated the protective activity of radicicol, an antifungal antibiotic, against inflammation-induced neurotoxicity in neuron–glia cultures. Radicicol potently prevented the loss of neuronal cell bodies and neurites from LPS/IFN-γ-induced neurotoxicity in rat cortical neuron–glia cultures with an EC 50 value of 0.09 μM. Radicicol inhibited the LPS/IFN-γ-induced expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) in microglia. Additionally, radicicol decreased the LPS/IFN-γ-induced release of tumor necrosis factor-α (TNF-α) in the cultures. The inhibitory potency of radicicol against the production of NO and TNF-α was well correlated with the protection of neurons. These results suggest that the protective effect of radicicol against LPS/IFN-γ-induced neuronal cell death in neuron–glia cultures is mediated via the inhibition of TNF-α release, as well as the suppression of iNOS expression in microglia.