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-alpha, NO and COX-2 expression in LOS-stimulated macrophages, without reducing the expression of IL-6. Furthermore, the phosphorylation of p38, JNK1/2, PKC-alpha and PKC-epsilon induced by LIDS was inhibited by osthole; however, the phosphorylation of ERK1/2 and PKC-delta was not reduced by osthole. Osthole also inhibited NF-kappa B activation and ROS release in LOS-stimulated macrophages. Our current results indicated that osthole is the major anti-inflammatory ingredient of Cnidium monnieri seed ethanol extract.