title: Saucerneol D inhibits eicosanoid generation and degranulation through suppression of Syk kinase in mast cells.
abstract: Previously we reported that saucerneol D (SD), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis) suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. The aim of this study was to elucidate whether SD modulates the generation of other inflammatory mediators in activated mast cells. We investigated the effects of SD on cyclooxygenase-2 (COX-2)-dependent prostaglandin D(2) (PGD(2)) and 5-lipoxygenase (5-LO)-dependent leukotriene C(4) (LTC(4)) generations as well as degranulation in cytokine-stimulated mouse bone marrow-derived mast cells (BMMCs). Biochemical analyses of the cytokine-mediated signaling pathways showed that SD suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes including phospholipase Cγ1 (PLCγ1)-mediated intracellular Ca(2+) influx and activation of mitogen-activated protein kinases (MAPKs; including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH(2)-terminal kinase (JNK) and p38) and the nuclear factor-κB (NF-κB) pathway. Taken together, the present study suggests that SD suppresses eicosanoid generation and degranulation through Syk-dependent pathway in BMMCs.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Chang-Seob
authors.initials: CS
authors.lastname: Seo
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015777:Eicosanoids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D017997:Leukotriene C4 / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D032134:Saururaceae / Q000737:chemistry; D000072377:Syk Kinase
chemical_list: D015777:Eicosanoids; D047908:Intracellular Signaling Peptides and Proteins; D017705:Lignans; D016328:NF-kappa B; D010936:Plant Extracts; C561428:saucerneol D; D017997:Leukotriene C4; D001094:Arachidonate 5-Lipoxygenase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D051966:Phospholipase C gamma; C117399:Plcg1 protein, mouse