title: Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway.
abstract: Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that arctigenin exerted its anti-inflammatory effect by inhibiting ROS-dependent STAT signaling through its antioxidant activity. Arctigenin also significantly reduced the phosphorylation of STAT1 and STAT 3 as well as JAK2 in LPS-stimulated RAW264.7 cells. The inhibitions of STAT1 and STAT 3 by arctigenin prevented their translocation to the nucleus and consequently inhibited expression of iNOS, thereby suppressing the expression of inflammation-associated genes, such as IL-1β, IL-6 and MCP-1, whose promoters contain STAT-binding elements. However, COX-2 expression was slightly inhibited at higher drug concentrations (50 μM). Our data demonstrate that arctigenin inhibits iNOS expression via suppressing JAK-STAT signaling pathway in macrophages.
authors.affiliation: Tongji Medical College, Huazhong University of Science and Technology, PR China.
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Kou
authors.forename: Shimei
authors.initials: S
authors.lastname: Qi
authors.forename: Wuxing
authors.initials: W
authors.lastname: Dai
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004347:Drug Interactions; D005663:Furans / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D051546:Cyclooxygenase 2; D005663:Furans; D053583:Interleukin-1beta; D015850:Interleukin-6; D053614:Janus Kinase 2; D017705:Lignans; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D052247:Nitric Oxide Synthase Type II; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C491768:Ccl2 protein, mouse; C513339:Romo1 protein, mouse; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; C507926:Jak2 protein, mouse; C071942:arctigenin