Attenuation of Neuroinflammatory Effects by Hippocampus KudaBleeler Derived Compounds, SE-1 and SE-2 via MAPK and NF-κB Signaling Pathways

Abstract

Inflammation has recently been implicated as a critical mechanism responsible for neurodegenerative diseases. Microglial cells and macrophages are responsible for mediating inflammatory responses related to neurodegeneration. The two compounds isolated from sea horse Hippocampus KudaBleeler; 1-(5-bromo-2-hydroxy-4-methoxyphenyl) ethanone [SE-1] and 1-(2-hydroxy-4-methoxyphenyl) ethanone [SE-2] were studied as agents to suppress lipopolysaccharide (LPS) mediated inflammatory responses in cultured BV-2 microglial cells and RAW264.7 macrophage cells. SE-1 and SE-2 significantly attenuated LPS induced release of inflammatory products such as nitric oxide, prostaglandin E2, reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The compounds also down regulated the protein and gene expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6 in both cell lines. Molecular signaling pathway studies showed that SE-1 and SE-2 inhibited the nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits by attenuating the IKKα/β (IκB kinase α/β) and IκBα. Also SE-1 and SE-2 suppressed the phosphorylation of MAPK molecules; JNK and p38 in both cell lines. These results suggest the potential in vitro anti-inflammatory activity of SE-1 and SE-2, which inhibited the LPS, stimulated inflammatory responses in BV-2and RAW264.7cells via suppressing MAPK and NF-κB signaling pathways.