title: Meliae cortex extract exhibits anti-allergic activity through the inhibition of Syk kinase in mast cells.
abstract: The anti-allergic action of various Oriental medicinal herbs was investigated using in vitro and in vivo experimental models. Of these extracts, the ethanol extract of Meliae cortex (MC) exhibited the most potent activity in mast cells; its IC(50) values were 29+/-1.5 microg/ml for antigen stimulation and 57+/-3.4 microg/ml for thapsigargin stimulation. It inhibited compound-48/80-induced systemic anaphylaxis by 52.9% at a dose of 300 mg/kg in mice; it also inhibited the expression of the proinflammatory mediator TNF-alpha. With regard to its mechanism of action, MC suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signaling processes and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. Taken together, these results suggest that the anti-allergic activity of MC may be due to the inhibition of histamine secretion and cytokine expression through the Syk inhibition in mast cells.
authors: College of Medicine, Konkuk University, Chungju 380-701, South Korea.
authors: Jun Ho
authors: JH
authors: Lee
authors: Na Young
authors: NY
authors: Ko
authors: Nam Wook
authors: NW
authors: Kim
authors: Se Hwan
authors: SH
authors: Mun
authors: Jie Wan
authors: JW
authors: Kim
authors: Erk
authors: E
authors: Her
authors: Bo Kyung
authors: BK
authors: Kim
authors: Dong Wan
authors: DW
authors: Seo
authors: Hyun Wook
authors: HW
authors: Chang
authors: Tae Chul
authors: TC
authors: Moon
authors: Jeung Whan
authors: JW
authors: Han
authors: Young Mi
authors: YM
authors: Kim
authors: Wahn Soo
authors: WS
authors: Choi
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D031586:Melia azedarach / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000072377:Syk Kinase; D019284:Thapsigargin / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
chemical_list: D018926:Anti-Allergic Agents; D047908:Intracellular Signaling Peptides and Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003189:p-Methoxy-N-methylphenethylamine; D019284:Thapsigargin; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D020928:Mitogen-Activated Protein Kinases