title: Neuroprotective role of tripchlorolide on inflammatory neurotoxicity induced by lipopolysaccharide-activated microglia.
abstract: A large body of evidence has suggested a strong association between neuroinflammation and the pathogenesis of many neurodegenerative diseases. Therefore, it is a good target for therapeutic treatment. So far, studies have proven anti-inflammatory herbal medicine and its constituents to be effective in slowing down the neurodegenerative process. The present study tested tripchlorolide, an extract of Tripterygium wilfordii Hook F (TWHF), as a novel agent to suppress inflammatory process in microglia. It showed this novel agent to be cytotoxic at a dose of 20-40 nM to primary microglia and BV-2 microglial cells but not to primary cortical neurons and Neuro-2A cells in vitro. Moreover, tripchlorolide protected primary cortical neurons and Neuro-2A cells from neuroinflammatory toxicity induced by the conditioned media from lipopolysaccharide (LPS)-stimulated microglia, which resulted in a significant decrease in their cell survival. The changes of the inflammatory mediators in this process were further investigated. In the LPS-stimulated microglia, the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO), prostaglandin E(2) (PGE(2)), and intracellular superoxide anion (SOA) was markedly attenuated by tripchlorolide at a dose of 1.25-10 nM in a dose-dependent manner. Furthermore, the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was also significantly inhibited by tripchlorolide in both mRNA and protein levels. These results suggest that tripchlorolide can protect neuronal cells via a mechanism involving inhibition of inflammatory responses of microglia to pathological stimulations. Therefore, it is potentially a highly effective therapeutic agent in treating neuroninflammatory diseases.
authors.affiliation: Department of Neurology, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian 350001, People's Republic of China.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Pan
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Chen
authors.forename: Yuan-gui
authors.initials: YG
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Tian-wen
authors.initials: TW
authors.lastname: Huang
authors.forename: Li-min
authors.initials: LM
authors.lastname: Chen
authors.forename: Qin-yong
authors.initials: QY
authors.lastname: Ye
authors.forename: Hua-pin
authors.initials: HP
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000276:immunology; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D009474:Neurons / Q000187:drug effects* / Q000276:immunology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000276:immunology / Q000517:prevention & control; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D004224:Diterpenes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; C068051:tripchlorolide; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone