title: Manassantin B isolated from Saururus chinensis inhibits cyclooxygenase-2-dependent prostaglandin D2 generation by blocking Fyn-mediated nuclear factor-kappaB and mitogen activated protein kinase pathways in bone marrow derived-mast cells.
abstract: The authors investigated the effect of manassantin B (Man B) isolated from Saururus chinensis (S. chinensis) on cyclooxygenase-2 (COX-2)-dependent prostaglandin D2 (PGD2) generation in mouse bone marrow derived-mast cells (BMMCs). Man B inhibited the generation of PGD2 dose-dependently by inhibiting COX-2 expression in immunoglobulin E (IgE)/Ag-stimulated BMMCs. To elucidate the mechanism responsible for the inhibition of COX-2 expression by Man B, the effects of Man B on the activation of nuclear factor-kappaB (NF-κB), a transcription factor essential and mitogen-activated protein kinases (MAPKs) for COX-2 induction, were examined. Man B attenuated the nuclear translocation of NF-κB p65 and its DNA-binding activity by inhibiting inhibitors of kappa Bα (IκBα) degradation and concomitantly suppressing IκB kinase (IKK) phosphorylation. In addition, Man B suppressed phosphorylation of MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38. It was also found that Man B suppressed Fyn kinase activation and consequent downstream signaling processes, including those involving Syk, Gab2, and Akt. Taken together, the present results suggest that Man B suppresses COX-2 dependent PGD2 generation by primarily inhibiting Fyn kinase in FcεRI-mediated mast cells.
authors.affiliation: College of Pharmacy, Yeungnam University; Gyeongsan 712–749, Republic of Korea.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Seung-Lark
authors.initials: SL
authors.lastname: Hwang
authors.forename: Jong Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D018517:Plant Roots / Q000737:chemistry; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D032134:Saururaceae
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005663:Furans; D016328:NF-kappa B; C482885:manassantin B; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D020928:Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2