Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway

• Published in: International immunopharmacology 2011-08, Vol.11 (8), p.1095-1102
• Main Authors: Kou, Xianjuan, Qi, Shimei, Dai, Wuxing, Luo, Lan, Yin, Zhimin
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammation; Anti-Inflammatory Agents - pharmacology; Arctigenin; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Chemokine CCL2 - antagonists & inhibitors; Chemokine CCL2 - genetics; Cyclooxygenase 2 - metabolism; Drug Interactions; Furans - pharmacology; iNOS; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - genetics; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - genetics; JAK-STAT; Janus Kinase 2 - antagonists & inhibitors; Janus Kinase 2 - metabolism; Lignans - pharmacology; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - metabolism; Mice; Mitochondrial Proteins - antagonists & inhibitors; Mitochondrial Proteins - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Pharmacology. Drug treatments; Phosphorylation - drug effects; Promoter Regions, Genetic - drug effects; Signal Transduction - drug effects; STAT1 Transcription Factor - antagonists & inhibitors; STAT1 Transcription Factor - metabolism; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2011.03.005

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.