title: 1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] suppresses pro-inflammatory responses by blocking NF-κB and MAPK signaling pathways in activated microglia.
abstract: Unregulated activation of microglia is a key risk factor contributes to neurodegenerative diseases and suppression of this phenomenon is considered as a potential therapeutic target. The compound isolated from sea horse Hippocampus kuda Bleeler; 1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] was characterized for its ability in suppressing LPS mediated activation of murine BV-2 cells. Despite the presence of various active molecular groups in the structure, SE1 has not well explored for its biological activities. The outcome of this study clearly indicated that SE1 inhibited the production of inflammatory mediators; nitric oxide, prostaglandin E(2) and pro-inflammatory cytokines. Furthermore, it inhibited the protein and gene expression levels of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β and interleukin-6. The responsible signaling mechanisms leading to these inhibitions were identified as SE1 mediated blocking of phosphorylation of mitogen activate protein kinase (MAPK) molecules; C-jun-N-terminal kinase (JNK), p38 and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits. These results suggest that SE1 has the potential to be further developed as therapeutic against neuro-inflammation.
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Department of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: S W A
authors.initials: SW
authors.lastname: Himaya
authors.forename: Bomi
authors.initials: B
authors.lastname: Ryu
authors.forename: Zhong-Ji
authors.initials: ZJ
authors.lastname: Qian
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000098:Acetophenones / Q000494:pharmacology* / Q000633:toxicity; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008422:Materials Testing; D017628:Microglia / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D023701:Smegmamorpha
chemical_list: C570286:1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone; D000098:Acetophenones; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone