title: 1-O-tigloyl-1-O-deacetyl-nimbolinin B inhibits LPS-stimulated inflammatory responses by suppressing NF-κB and JNK activation in microglia cells.
abstract: Overactivation of microglia may contribute to the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and HIV dementia. Thus, regulating microglial activation has been an important therapeutic strategy for treating neurodegenerative diseases. In this research, we compared three limonoids compounds extracted from Melia toosendan by a cell-based assay to investigate their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated microglia cells. Our study indicated that 1-O-tigloyl-1-O-deacetyl-nimbolinin B (TNB) markedly suppressed the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in LPS-stimulated microglia cells. TNB also inhibited the gene expression of inducible nitric oxide synthase (iNOS), TNF-α, cyclooxygenase (COX-2), and interleukin (IL)-1β. In addition, TNB inhibited generation of intracellular reactive oxygen species (ROS). We found that TNB significantly attenuated the nuclear translocation of NF-κB, inhibiting the activation of c-jun N-terminal kinase (JNK) in LPS-stimulated BV-2 cells. Furthermore, TNB reduced cytotoxicity of activated microglia toward HT-22 hippocampal cells in a co-culture system. Taken together, our experimental results reveal, for the first time, that TNB is a potent inhibitor of microglia-mediated inflammation, and it might be a potential candidate for the treatment of neurodegenerative diseases.
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Fali
authors.initials: F
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Hao
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.forename: Jiang-yun
authors.initials: JY
authors.lastname: Liu
authors.forename: Long Tai
authors.initials: LT
authors.lastname: Zheng
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics*; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D036701:Limonins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000009:adverse effects*; D031585:Melia / Q000737:chemistry; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C000596269:1-O-tigloyl-1-O-deacetylnimbolinin B; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D036701:Limonins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases