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

• Main Authors: Hadi Supriady, Muhamad Noor Alfarizal Kamarudin, Chim Kei Chan, Bey Hing Goh, Habsah Abdul Kadir
• Format: Article
• Language: English
• Published: Elsevier 2015-08-01
• Series: Journal of Functional Foods
• Subjects: Swietenia macrophylla; Anti-inflammatory; BV-2 microglial cells; MAPKs; Akt; NF-κB
• Online Access: http://www.sciencedirect.com/science/article/pii/S1756464615002819
• ISSN: 1756-4646

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-α (TNF-α) and interleukin-6 (IL-6). SMEAF inhibited nuclear translocation of nuclear factor-kappa B (NF-κB) via the attenuation of IκBα 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-κB, 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-κB, 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.