Nargenicin attenuates lipopolysaccharide-induced inflammatory responses in BV-2 cells

Microglia activation has been considered as a major factor associated with neurodegenerative diseases. In this study, we investigated the inhibitory effects of nargenicin, a natural antibiotic from soil bacterium Nocardia, on lipopolysaccharide (LPS)-induced inflammatory activation of microglia. Nargenicin significantly attenuated LIPS-induced nitric oxide production in BV-2 microglial cells. Furthermore, nargenicin effectively suppressed the upregulation of interleukin-1 beta, tumor necrosis factor alpha, and inducible nitric oxide synthase at both mRNA and protein levels in LIPS-stimulated BV-2 microglia. In addition, nargenicin blocked LPS-induced degradation of I kappa B-alpha, indicating that the initial molecular target of nargenicin is the transcription factor nuclear factor-kappa B. These results suggest that nargenicin should be evaluated as a therapeutic agent for inflammatory neurodegenerative diseases. NeuroReport 20:1007-1012 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.