Osthole regulates inflammatory mediator expression through modulating NF-κB, mitogen-activated protein kinases, protein kinase C, and reactive oxygen species.
Osthole, a coumarin compound, has been reported to exhibit various biological activities; however the cellular mechanism of its immune modulating activity has not yet been fully addressed. In this study we isolated osthole from the seeds of Cnidium monnieri and demonstrated that osthole inhibited TNF-α, NO and COX-2 expression in LPS-stimulated macrophages, without reducing the expression of IL-6. Furthermore, the phosphorylation of p38, JNK1/2, PKC-α and PKC-ε induced by LPS was inhibited by osthole; however, the phosphorylation of ERK1/2 and PKC-δ was not reduced by osthole. Osthole also inhibited NF-κB activation and ROS release in LPS-stimulated macrophages. Our current results indicated that osthole is the major anti-inflammatory ingredient of Cnidium monnieri seed ethanol extract.
Liao
Pei-Chun
PC
Institute of Biotechnology, National Ilan University, Ilan, Taiwan.
Chien
Shih-Chang
SC
Ho
Chen-Lung
CL
Wang
Eugene I-Chen
EI
Lee
Shu-Ching
SC
Kuo
Yueh-Hsiung
YH
Jeyashoke
Narumon
N
Chen
Jie
J
Dong
Wei-Chih
WC
Chao
Louis Kuoping
LK
Hua
Kuo-Feng
KF
D000276:Adjuvants, Immunologic; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D031048:Cnidium / Q000737:chemistry*; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis; D010936:Plant Extracts / Q000737:chemistry; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D012639:Seeds / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D003374:Coumarins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C046627:osthol