Anti-neuroinflammatory effect of aurantiamide acetate from the marine fungus Aspergillus sp SF-5921: Inhibition of NF-κB and MAPK pathways in lipopolysaccharide-induced mouse BV2 microglial cells

In the course of a search for anti-neuroinflammatory metabolites from marine fungi, aurantiamide acetate (1) was isolated from marine-derived Aspergillus sp. as an anti-neuroinflammatory component. Compound 1 dose-dependently inhibited the production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) in BV2 microglial cells. It also attenuated inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and other pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). In a further study designed to elucidate the mechanism of its anti-neuroinflammatory effect, compound 1 was shown to block the activation of nuclear factor-kappa B (NF-kappa B) in lipopolysaccharide (LPS)-induced BV2 microglial cells by inhibiting the phosphorylation of the inhibitor kappa B-alpha (I kappa B)-alpha. In addition, compound 1 decreased the phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs). These results suggest that compound 1 has an anti-neuroinflammatory effect on LPS stimulation through its inhibition of the NF-kappa B, JNK and p38 pathways. (C) 2014 Elsevier B.V. All rights reserved.