title: L-3-n-Butylphthalide attenuates neuroinflammatory responses by downregulating JNK activation and upregulating Heme oxygenase-1 in lipopolysaccharide-treated mice.
abstract: Microglia activation-induced neuroinflammation contributes to neuronal damage in neurodegenerative diseases. Inhibition of microglia activation and reduction of major neurotoxic cytokines have been becoming a therapeutic strategy for neurodegenerative diseases. L-3-n-Butylphthalide (L-NBP) has shown the potent neuroprotective effects in stroke and Alzheimer's disease animal models. The present study investigated the immune modulatory effects of L-NBP on pro-inflammatory cytokines and microglia activation in brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Our results showed that systemic LPS treatment induced microglia activation in the brain. L-NBP treatment significantly suppressed the expression of proinflammatory cytokines, such as tumor necrosis factor (TNFα), interlukin-1β (IL-1β), interlukin-6 (IL-6), and interlukin-10 (IL-10) in LPS-treated mice. At the meantime, L-NBP treatment decreased the morphological activation of microglia. In addition, the phosphorylation level of JNK MAP kinase-signaling pathway was also inhibited by L-NBP in LPS-treated mice. Furthermore, L-NBP upregulated the expression of heme oxygenase (HO)-1, a key element in the anti-inflammation and anti-oxidative stress. These results suggested that L-NBP might be a promising candidate in delaying and reversing the progress of neurodegenerative diseases by inhibiting microglia activation.
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Zhao
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lei
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Xu
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001572:Benzofurans; D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C027125:3-n-butylphthalide; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases
keywords: JNK; L-3-n-butylphthalide; lipopolysaccharide; neuroinflammatory response