PMID- 23719635 OWN - NLM STAT- MEDLINE DCOM- 20140221 LR - 20190720 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 36 IP - 8 DP - 2013 TI - 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. PG - 1370-4 AB - 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-kappaB), a transcription factor essential and mitogen-activated protein kinases (MAPKs) for COX-2 induction, were examined. Man B attenuated the nuclear translocation of NF-kappaB p65 and its DNA-binding activity by inhibiting inhibitors of kappa Balpha (IkappaBalpha) degradation and concomitantly suppressing IkappaB 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 FcepsilonRI-mediated mast cells. FAU - Lu, Yue AU - Lu Y AD - College of Pharmacy, Yeungnam University; Gyeongsan 712-749, Republic of Korea. FAU - Hwang, Seung-Lark AU - Hwang SL FAU - Son, Jong Keun AU - Son JK FAU - Chang, Hyeun Wook AU - Chang HW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130528 PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 0 (Furans) RN - 0 (NF-kappa B) RN - 0 (manassantin B) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.10.2 (Fyn protein, mouse) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - RXY07S6CZ2 (Prostaglandin D2) SB - IM MH - Animals MH - Bone Marrow Cells/cytology MH - Cells, Cultured MH - Cyclooxygenase 2/metabolism MH - Cyclooxygenase 2 Inhibitors/isolation & purification/*pharmacology MH - Furans/isolation & purification/*pharmacology MH - Male MH - Mast Cells/*drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/metabolism MH - Phytotherapy MH - Plant Roots/chemistry MH - Prostaglandin D2/*antagonists & inhibitors/metabolism MH - Proto-Oncogene Proteins c-fyn/metabolism MH - Saururaceae EDAT- 2013/05/31 06:00 MHDA- 2014/02/22 06:00 CRDT- 2013/05/31 06:00 PHST- 2013/05/31 06:00 [entrez] PHST- 2013/05/31 06:00 [pubmed] PHST- 2014/02/22 06:00 [medline] AID - DN/JST.JSTAGE/bpb/b13-00146 [pii] AID - 10.1248/bpb.b13-00146 [doi] PST - ppublish SO - Biol Pharm Bull. 2013;36(8):1370-4. doi: 10.1248/bpb.b13-00146. Epub 2013 May 28.