title: A novel synthetic HTB derivative, BECT inhibits lipopolysaccharide-mediated inflammatory response by suppressing the p38 MAPK/JNK and NF-κB activation pathways.
abstract: Activated microglia cells are well recognized as mediators of neuroinflammation, as they release nitric oxide and pro-inflammatory cytokines in various neuroinflammatory diseases. Thus, suppressing microglial activation may alleviate neuroinflammatory and neurodegenerative processes. In the present study, we synthesized and investigated the anti-neuroinflammatory effect of a novel HTB (2-hydroxy-4-trifuoromethylbenzoic acid) derivative in lipopolysaccharide (LPS)-stimulated microglial cells. Among the synthesized derivatives, the BECT [But-2-enedioic acid bis-(2-carboxy-5-trifluoromethyl-phenyl) ester] significantly decreased production of nitric oxide and other pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in microglial cells. BECT also mitigated the expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. Further mechanistic studies demonstrated that the HTB derivative inhibited phosphorylation of JNK and p38 mitogen-activated protein kinase and nuclear translocation of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells. Thus BECT, our novel synthesized compound have anti-inflammatory activity in microglial cells, and may have therapeutic potential for treating neuroinflammatory diseases.
authors.affiliation: Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Seong-Mook
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Sandeep Vasant
authors.initials: SV
authors.lastname: More
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Byung-Wook
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Park Jeong
authors.initials: PJ
authors.lastname: In
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea. Electronic address: choidk@kku.ac.kr.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012459:Salicylates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012459:Salicylates; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C033502:4-trifluoromethylsalicylic acid; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases
keywords: HTB derivative; Lipopolysaccharide; Microglia; Neurodegenerative disease; Neuroinflammation