title: Antiinflammatory effects of orientin-2"-O-galactopyranoside on lipopolysaccharide-stimulated microglia.
abstract: Microglia activation-mediated neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and human immunodeficiency virus (HIV)-associated dementia. Inhibition of microglia activation may alleviate neurodegeneration under neuroinflammatory conditions. In the present study, we compared three flavone C-glycosides extracted from Trollius chinensis BUNGE using a cell-based assay to evaluate their antiinflammatory effects on microglial cells. The results showed that orientin-2"-O-galactopyranoside (OGA) significantly inhibited the production of nitric oxide and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated microglial cells. OGA also markedly inhibited the LPS-induced expression of TNF-α, interleukin-1β, inducible nitric oxide (NO) synthase, and cyclooxygenase-2, which was accompanied by suppression of the activation of nuclear factor (NF)-κB and the extracellular signal-regulated kinase (ERK) signal pathway. In addition, OGA decreased LPS-induced reactive oxygen species generation, which appears to be related to the activation of the NF-E2-related factor2 (NRF2)/ heme oxygenase-1 (HO-1) pathway in BV-2 microglial cells. Furthermore, OGA reduced the cytotoxicity of activated microglia toward HT-22 neuroblastoma cells in a co-culture system. Taken together, the present study demonstrated that the induction of HO-1-mediated inhibition of the NF-κB and ERK pathways contributes significantly to the antineuroinflammatory and neuroprotective effects elicited by OGA.
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Gan
authors.forename: Lili
authors.initials: L
authors.lastname: Hao
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Jia
authors.initials: J
authors.lastname: Jia
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
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 / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D005697:Galactosides / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047309:Flavones; D005697:Galactosides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; C000596493:orientin-2''-O-galactopyranoside; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases