Meliae cortex extract exhibits anti-allergic activity through the inhibition of Syk kinase in mast cells.
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.
Lee
Jun Ho
JH
College of Medicine, Konkuk University, Chungju 380-701, South Korea.
Ko
Na Young
NY
Kim
Nam Wook
NW
Mun
Se Hwan
SH
Kim
Jie Wan
JW
Her
Erk
E
Kim
Bo Kyung
BK
Seo
Dong Wan
DW
Chang
Hyun Wook
HW
Moon
Tae Chul
TC
Han
Jeung Whan
JW
Kim
Young Mi
YM
Choi
Wahn Soo
WS
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
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