PMID- 22863941 OWN - NLM STAT- MEDLINE DCOM- 20121221 LR - 20190720 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 35 IP - 8 DP - 2012 TI - Pinusolide isolated from Biota orientalis inhibits 5-lipoxygenase dependent leukotriene C4 generation by blocking c-Jun N-terminal kinase pathway in mast cells. PG - 1374-8 AB - Pinusolide, an herbal medicine isolated from Biota orientalis L. (B. orientalis), inhibited 5-lipoxygenase (5-LO)-dependent leukotriene C4 (LTC4) generation in immunoglobulin E (IgE)/Ag-induced bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner. To clarify the action mechanism of pinusolide on the inhibition of LTC4 generation, we examined the effect of pinusolide on phosphorylation of cytosolic phospholipase A2 (cPLA2), as well as translocation phospho-cPLA2 and 5-LO to nucleus. Inhibition of LTC4 generation by pinusolide was accompanied by a decrease in cPLA2 phosphorylation which occurred via a decrease in intracellular Ca2+ influx and blocking the c-Jun N-terminal kinase (JNK) pathways. However, pinusolide had no effect on extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinas phosphorylation. Taken together, the present results suggest that potent inhibition of 5-LO dependent LTC4 generation by pinusolide requires both suppression of calcium influx and JNK phosphorylation. FAU - Jin, Ye AU - Jin Y AD - College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. FAU - Yang, Hyun Ok AU - Yang HO 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 PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Diterpenes) RN - 0 (Plant Extracts) RN - 2CU6TT9V48 (Leukotriene C4) RN - 31685-80-0 (pinusolide) RN - 37341-29-0 (Immunoglobulin E) RN - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 3.1.1.4 (Phospholipases A2) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Anti-Inflammatory Agents/isolation & purification/pharmacology MH - Arachidonate 5-Lipoxygenase/*metabolism MH - Biological Transport MH - Bone Marrow MH - Calcium/*metabolism MH - Cell Nucleus MH - Cytosol MH - Diterpenes/isolation & purification/*pharmacology MH - Dose-Response Relationship, Drug MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Immunoglobulin E/metabolism MH - JNK Mitogen-Activated Protein Kinases/*metabolism MH - Leukotriene C4/*biosynthesis MH - Male MH - Mast Cells/*drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Phospholipases A2/metabolism MH - Phosphorylation MH - Plant Extracts/chemistry/pharmacology MH - Signal Transduction MH - Thuja/*chemistry EDAT- 2012/08/07 06:00 MHDA- 2012/12/22 06:00 CRDT- 2012/08/07 06:00 PHST- 2012/08/07 06:00 [entrez] PHST- 2012/08/07 06:00 [pubmed] PHST- 2012/12/22 06:00 [medline] AID - DN/JST.JSTAGE/bpb/b12-00271 [pii] AID - 10.1248/bpb.b12-00271 [doi] PST - ppublish SO - Biol Pharm Bull. 2012;35(8):1374-8. doi: 10.1248/bpb.b12-00271.