title: Catalpol inhibits LPS plus IFN-γ-induced inflammatory response in astrocytes primary cultures.
abstract: A large body of evidence suggests that the inflammatory reaction plays an important role in the pathogenesis of neurodegenerative diseases. Our previous studies described the neuroprotective effects of catalpol in lipopolysaccharide (LPS)-induced inflammatory models, in which catalpol was shown to prevent mesencephalic neuron death and ameliorate cognitive ability animals. To further investigate the protective effect and underlying mechanism of catalpol, astrocytes were pretreated with low (0.1mM) and high dose (0.5mM) catalpol for 1h prior to LPS plus interferon-γ stimulation. Biochemical analyses showed that NO and ROS production and iNOS activity were significantly reduced by catalpol. Data at transcriptional level also demonstrated that catalpol potently attenuated gene expressions involved in inflammation, such as iNOS, COX-2 and TLR4. In addition, our exploration further revealed that the suppressive action of catalpol on inflammation was mediated via inhibiting nuclear factor-κB (NF-κB) activation. Collectively, these results suggest that catalpol can exert inhibitory effects on the inflammatory reaction in astrocytes and that inactivation of NF-κB could be the major determinant for its anti-inflammatory mechanism. Therefore, catalpol may potentially be a highly effective therapeutic agent in treating neurodegenerative diseases associated with inflammation.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Andrew
authors.initials: A
authors.lastname: Zorn
authors.forename: Rong-Guo
authors.initials: RG
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: An
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007371:Interferon-gamma; D057888:Iridoid Glucosides / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D057888:Iridoid Glucosides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C078040:catalpol; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2