Forsythin inhibits lipopolysaccharide-induced inflammation by suppressing JAK-STAT and p38 MAPK signalings and ROS production

• Published in: Inflammation research Vol. 63; no. 7; pp. 597 - 608
• Main Authors: Pan, Xiaolong, Cao, Xiang, Li, Na, Xu, Yimiao, Wu, Qiuyue, Bai, Jing, Yin, Zhimin, Luo, Lan, Lan, Lei
• Format: Journal Article
• Language: English
• Published: Basel Springer Basel 01.07.2014; Springer Nature B.V
• Subjects: Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Cell Line; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cytokines - metabolism; Dermatology; Forsythia suspensa; Furans - pharmacology; Immunology; Janus Kinases - antagonists & inhibitors; Janus Kinases - metabolism; Lipopolysaccharides; Mice; Neurology; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Original Research Paper; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pharmacology/Toxicology; Reactive Oxygen Species - metabolism; Rheumatology; Signal Transduction - drug effects; STAT Transcription Factors - antagonists & inhibitors; STAT Transcription Factors - metabolism; RAW264.7 cells; Forsythin; JAK-STATs; p38 MAPKs; ROS
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-014-0731-7

Objective Forsythin (FOR) is an active ingredient extracted from the fruit of the medicinal plant Forsythia suspensa (Thunb.) Vahl. Here, we investigated the effect of FOR on LPS-induced inflammatory response and the underlying molecular mechanisms in RAW264.7 macrophages. Materials and methods RAW264.7 cells were pre-treated with or without FOR and then stimulated with or without LPS. The productions of TNF-α, IL-1β, IL-6, PGE 2 and NO were determined by ELISA and nitrite analysis, respectively. The expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blotting and RT-PCR analysis. The activations of signaling molecules were detected by Western blotting using phosphorylation specific antibodies. Reactive oxygen species (ROS) production was determined by ROS assay. Results LPS-induced productions of IL-1β, IL-6, TNF-α, NO and PGE 2 were inhibited by FOR in a dose-dependent manner. FOR also suppressed the LPS-elevated expressions of iNOS and COX-2. Further investigations revealed that FOR significantly inhibited the LPS-induced activations of JAK-STATs and p38 MAPKs, but not of IKKα/β in LPS-stimulated RAW264.7 cells. Additionally, FOR interfered with both JAK-STATs and p38 MAPKs signaling pathways to modulate the expressions of IL-1β, IL-6, TNF-α, iNOS and COX-2. Furthermore, FOR reduced the LPS-induced ROS accumulation, validating that FOR serves as an antioxidant. Conclusions Our data suggested that FOR exerts anti-inflammatory action, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signalings and production of ROS in macrophage cells.