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 LPS-induced nitric oxide production in BV-2 microglial cells. Furthermore, nargenicin effectively suppressed the upregulation of interleukin-1beta, tumor necrosis factor alpha, and inducible nitric oxide synthase at both mRNA and protein levels in LPS-stimulated BV-2 microglia. In addition, nargenicin blocked LPS-induced degradation of IkappaB-alpha, indicating that the initial molecular target of nargenicin is the transcription factor nuclear factor-kappaB. These results suggest that nargenicin should be evaluated as a therapeutic agent for inflammatory neurodegenerative diseases.