title: Pinusolide isolated from Biota orientalis inhibits 5-lipoxygenase dependent leukotriene C4 generation by blocking c-Jun N-terminal kinase pathway in mast cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712–749, Republic of Korea.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jin
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
authors.forename: Jong Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001692:Biological Transport; D001853:Bone Marrow; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus; D003600:Cytosol; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D054467:Phospholipases A2 / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction; D029783:Thuja / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D010936:Plant Extracts; D017997:Leukotriene C4; C101973:pinusolide; D007073:Immunoglobulin E; D001094:Arachidonate 5-Lipoxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D054467:Phospholipases A2; D002118:Calcium