Astragalus polysaccharide attenuates lipopolysaccharide-induced inflammatory responses in microglial cells: regulation of protein kinase B and nuclear factor-κB signaling

Microglia play an important role in immune and inflammatory responses in the central nervous system. Astragalus polysaccharide (APS) has been reported as an immune stimulant for various inflammation-associated diseases in vivo. The present study investigated the effects of APS on lipopolysaccharide-stimulated inflammatory responses in microglial cells. Cultured BV2 microglial cells were pre-treated with APS (0-200 mu g/ml) prior to lipopolysaccharide (50 ng/ml) stimulation. The production of proinflammatory mediators including inducible nitric oxide synthase (iNOS)/nitric oxide (NO), cyclooxygenase-2 (COX-2)/prostaglandin E (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) were evaluated. APS dose-dependently reduced lipopolysaccharide stimulated nitric oxide and PGE(2) production, as well as iNOS and cyclooxygenase-2 gene expression. It also attenuated proinflammatory cytokines IL-1 beta and TNF-alpha generation. In addition, APS inhibited nuclear factor-kappa B translocation by blockade of I kappa B degradation and suppressed protein kinase B phosphorylation in lipopolysaccharide-stimulated cells. The inhibitory effects of APS on lipopolysaccharide-stimulated inflammatory mediator production in microglia are associated with suppression of nuclear factor-kappa B and protein kinase B signaling pathways. APS may offer therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied with microglial activation.