PMID- 26675131 OWN - NLM STAT- MEDLINE DCOM- 20160906 LR - 20161126 IS - 1477-2213 (Electronic) IS - 1028-6020 (Linking) VI - 18 IP - 3 DP - 2016 TI - L-3-n-Butylphthalide attenuates neuroinflammatory responses by downregulating JNK activation and upregulating Heme oxygenase-1 in lipopolysaccharide-treated mice. PG - 289-302 LID - 10.1080/10286020.2015.1099524 [doi] AB - 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 (TNFalpha), interlukin-1beta (IL-1beta), 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. FAU - Zhao, Chun-Yang AU - Zhao CY AD - 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. FAU - Lei, Hui AU - Lei H AD - 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. FAU - Zhang, Yu AU - Zhang Y AD - 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. FAU - Li, Lin AU - Li L AD - 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. FAU - Xu, Shao-Feng AU - Xu SF AD - 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. FAU - Cai, Jie AU - Cai J AD - 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. FAU - Li, Ping-Ping AU - Li PP AD - 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. FAU - Wang, Ling AU - Wang L AD - 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. FAU - Wang, Xiao-Liang AU - Wang XL AD - 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. FAU - Peng, Ying AU - Peng Y AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151216 PL - England TA - J Asian Nat Prod Res JT - Journal of Asian natural products research JID - 100888334 RN - 0 (Benzofurans) RN - 0 (Cytokines) RN - 0 (Immunologic Factors) RN - 0 (Lipopolysaccharides) RN - 0 (Neuroprotective Agents) RN - 0 (TNF protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 822Q956KGM (3-n-butylphthalide) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Benzofurans/*pharmacology MH - Brain/drug effects MH - Cytokines/metabolism MH - Disease Models, Animal MH - Heme Oxygenase-1/*metabolism MH - Immunologic Factors/pharmacology MH - Inflammation/drug therapy MH - Lipopolysaccharides/*pharmacology MH - MAP Kinase Signaling System/drug effects MH - Mice MH - Mice, Inbred C57BL MH - Microglia/drug effects MH - Mitogen-Activated Protein Kinases/metabolism MH - Molecular Structure MH - Neuroprotective Agents/pharmacology MH - Phosphorylation/drug effects MH - Signal Transduction/drug effects MH - Tumor Necrosis Factor-alpha MH - Up-Regulation/drug effects OTO - NOTNLM OT - JNK OT - L-3-n-butylphthalide OT - lipopolysaccharide OT - neuroinflammatory response EDAT- 2015/12/18 06:00 MHDA- 2016/09/07 06:00 CRDT- 2015/12/18 06:00 PHST- 2015/12/18 06:00 [entrez] PHST- 2015/12/18 06:00 [pubmed] PHST- 2016/09/07 06:00 [medline] AID - 10.1080/10286020.2015.1099524 [doi] PST - ppublish SO - J Asian Nat Prod Res. 2016;18(3):289-302. doi: 10.1080/10286020.2015.1099524. Epub 2015 Dec 16.