SMEAF attenuates the production of pro-inflammatory mediators through the inactivation of Akt-dependent NF-kappa B, p38 and ERK1/2 pathways in LPS-stimulated BV-2 microglial cells

摘要

The ethyl acetate fraction from the seeds of Swietenia macrophylla (SMEAF) was studied for anti-inflammatory properties using lipopolysaccharide (LPS)-induced BV-2 microglia. SMEAF significantly attenuated the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). SMEAF inhibited nuclear translocation of nuclear factor-kappa B (NF-0) via the attenuation of I kappa B alpha phosphorylation. Moreover, SMEAF markedly suppressed phosphorylation of Akt, p38 Mitogen-activated protein kinase (MAPK) and Extracellular signal-regulated kinase 1/2 (ERK1/2) in LPS-induced BV-2 cells. Treatment with specific inhibitors for Akt, NF-kappa B, p38 and ERK1/2 resulted in the attenuation of iNOS and COX-2 protein expression. These findings indicated that SMEAF possesses anti-inflammatory activities in BV-2 cells by modulating LPS-induced pro-inflammatory mediator production via the inhibition of Akt-dependent NF-kappa B, p38 MAPK and ERK1/2 activation. These results further advocate the potential use of S. macrophylla as nutraceutical for the intervention of neurodegenerative and neuroinflammatory disorders. (C) 2015 Elsevier Ltd. All rights reserved.