title: Licarin A is a candidate compound for the treatment of immediate hypersensitivity via inhibition of rat mast cell line RBL-2H3 cells.
abstract: OBJECTIVE
  We previously demonstrated that some phenylpropanoids are capable of inhibiting activated mast cells. This study evaluated the anti-allergic effects of licarin A, a neolignan isolated from various plants, on antigen-stimulated rat mast cell line.
  
  
  METHODS
  The inhibitory effects of licarin A on histamine release, tumour necrosis factor-α (TNF-α) and prostaglandin D2 (PGD2) production, and cyclooxygenase-2 (COX-2) expression in dinitrophenyl-human serum albumin (DNP-HSA) rat basophilic leukemia cells (DNP-HSA-stimulated RBL-2H3 cells), were investigated by spectrofluorometry, ELISA and immunoblotting.
  
  
  RESULTS
  Licarin A significantly and dose-dependently reduced TNF-α production (IC50 12.6 ± 0.3 μm) in DNP-HSA-stimulated RBL-2H3 cells. Furthermore, the levels of PGD2 secretion in DNP-HSA-stimulated cells pretreated with licarin A were lower than those stimulated with DNP-HSA alone (positive control). Treatment with licarin A at 20 μm produced slight suppression of DNP-HSA-induced increases in COX-2 mRNA and protein levels. We identified several signalling pathways that mediated these pharmacological effects. Licarin A treatment tended to reduce phosphorylated protein kinase C alpha/beta II (PKCα/βII) and p38 mitogen-activated protein kinase (MAPK) protein levels.
  
  
  CONCLUSIONS
  Our results demonstrate that licarin A reduces TNF-α and PGD2 secretion via the inhibition of PKCα/βII and p38 MAPK pathways; this compound may be useful for attenuating immediate hypersensitivity.
authors.affiliation: Department of Physiology, Aichi Medical University, Aichi, Japan.|Faculty of Pharmacy, Meijo University, Aichi, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Faculty of Pharmacy, Meijo University, Aichi, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ito
authors.affiliation: Department of Physiology, Aichi Medical University, Aichi, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Masubuchi
authors.affiliation: School of Sport and Health Science, Tokai Gakuen University, Aichi, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Itoigawa
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004140:Dinitrophenols / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006636:Histamine Release / Q000187:drug effects; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000378:metabolism; D064546:Protein Kinase C beta / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051381:Rats; D012709:Serum Albumin / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; D004140:Dinitrophenols; D017705:Lignans; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; C058064:dinitrophenyl-human serum albumin conjugate; C432503:licarin A; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2
keywords: immediate hypersensitivity; licarin A; mast cell; prostaglandin D2; tumor necrosis factor-α