Imperatorin attenuates LPS-induced inflammation by suppressing NF-κB and MAPKs activation in RAW 264.7 macrophages.
Imperatorin is a type of coumarin compound with antibacterial and antiviral activities. In the present study, we examined the anti-inflammatory effects of imperatorin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by investigating its impact on the production and expression of cytokines and the major signal-transduction pathways. We found that imperatorin downregulated LPS-induced levels of TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages in a concentration-dependent manner, and it significantly inhibited expression of TNF-α and IL-6 (P < 0.05 or P < 0.01). The phosphorylation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-κB) p65 protein were analyzed by western blotting. In RAW 264.7 macrophages treated with 1 mg/L of LPS, imperatorin significantly inhibited p38 and Jun N-terminal kinase phosphorylation protein expression. However, there was no significant change in p-ERK. Furthermore, imperatorin also inhibited NF-κB translocation into the nucleus through blockage of IκBα phosphorylation and degradation.
Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin 130062, People's Republic of China.
Weixiao
W
Guo
Jingjing
J
Sun
Lanxiang
L
Jiang
Lingxin
L
Duan
Meixia
M
Huo
Na
N
Chen
Weiting
W
Zhong
Lanan
L
Wassy
Zhenguo
Z
Yang
Haihua
H
Feng
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D004789:Enzyme Activation / Q000187:drug effects; D011564:Furocoumarins / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D011564:Furocoumarins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C031534:imperatorin