title: Anti-neuroinflammatory effects of DPTP, a novel synthetic clovamide derivative in in vitro and in vivo model of neuroinflammation.
abstract: Neuroinflammation is one of the critical pathological mechanisms influencing various neurodegenerative disorders. Most of the neurodegenerative diseases involve over-activation of microglial cells contributing to the demise of neurons. The objective of the current study is to evaluate the anti-inflammatory effect of novel synthetic clovamide derivative on the suppression of microglial activation in an in vitro and in vivo model of neuroinflammation. We have used lipopolysaccharide (LPS) to induce an inflammatory response in murine BV-2 microglial cells. Molecular tools like immunocytochemistry and immunoblotting were used to study the activity of novel synthetic clovamide derivative to inhibit inflammation induced by LPS in microglial cells. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mouse model of neuroinflammation was developed to investigate the anti-neuroinflammatory effects of DPTP [3-(3,4-Dihydroxy-phenyl)-2-[4-(3-trifluoromethylphenyl)-but-2-enoylamino]-propionic acid methyl ester]. DPTP was observed to reduce the proinflammatory response in BV-2 cells induced by LPS. Further investigation revealed that DPTP attenuated phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), which was accompanied by a decrease in nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 microglia. Moreover, prophylactic treatment with DPTP (20mg/kg) for 7 days suppressed MPTP induced glial activation and behavioral impairment. Overall, our findings suggested that, DPTP exerts anti-neuroinflammatory effects against activated microglia in an in vitro and in vivo model and hence might be a promising therapeutic agent for alleviating the evolvement of neurodegenerative diseases associated with microglial activation.
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
authors.forename: Hyung-Woo
authors.initials: HW
authors.lastname: Lim
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
authors.forename: Jeong-In
authors.initials: JI
authors.lastname: Park
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
authors.forename: Sandeep Vasant
authors.initials: SV
authors.lastname: More
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, South Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea; Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
authors.forename: Byung-Wook
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Branches of Immune and Cell Therapy, National Cancer Center, Goyang, South Korea.
authors.forename: Sae-Bom
authors.initials: SB
authors.lastname: Jeon
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
authors.forename: Yo-sep
authors.initials: YS
authors.lastname: Yun
authors.affiliation: Branches of Immune and Cell Therapy, National Cancer Center, Goyang, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, South Korea.
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea. Electronic address: choidk@kku.ac.kr.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014443:Tyrosine; C416518:clovamide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Clovamide derivative; Lipopolysaccharide; MPTP; Microglia; Neuroinflammation