title: Norisoboldine inhibits the production of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells by down-regulating the activation of MAPKs but not NF-κB.
abstract: Norisoboldine is the main isoquinoline alkaloid occurring in Radix Linderae, the dry roots of Lindera aggregata (Lauraceae family). It has been previously implicated to be able to ameliorate the synovial inflammation and abnormal immune conditions in collagen-induced arthritis of mice. To get insight to the potential anti-inflammatory mechanisms of this alkaloid compound, the present study was undertaken to explore the effects of norisoboldine on the production of pro-inflammatory cytokines from macrophages stimulated by lipopolysaccharide. In vitro, norisoboldine substantially reduced the production of nitric oxide (NO), tumor necrosis factor (TNF)-α as well as interleukin (IL)-1β from RAW264.7 macrophage cells in a concentration-dependent manner, whereas it only slightly reduced the production of interleukin-6 (IL-6) at both protein and transcription levels. Of note, the preventive effects of norisoboldine on the release of pro-inflammatory cytokines were correlated with the inhibitory action on the phosphorylations of mitogen-activated protein (MAP) kinases including p38, extracellular signal-regulated kinase (ERK) and c-jun NH(2)-terminal kinase (JNK), but not on the activation and translocation of nuclear factor-κB (NF-κB). It can be therefore concluded that norisoboldine inhibits the macrophage activation and the resultant production of pro-inflammatory cytokines via down-regulating the activation of MAPKs signaling pathways rather than NF-κB.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Luo
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Yao
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Guixin
authors.initials: G
authors.lastname: Chou
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C464745:norisoboldine; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases