Camellia japonica suppresses immunoglobulin E-mediated allergic response by the inhibition of Syk kinase activation in mast cells.
BACKGROUND
Novel approaches are being explored to develop new therapies for various allergic diseases. Complementary and alternative medicines are considered to be promising avenues for the development of such new therapies.


OBJECTIVE
To investigate the effect of many Korean plants on the IgE-mediated allergic response in mast cells and in vivo, and its mechanism of action.


METHODS
The anti-allergic activity was tested by evaluating effects on degranulation of mast cells in culture and passive cutaneous anaphylaxis (PCA) in vivo. Its mechanism of action was investigated by immunoblotting analysis, immunoprecipitation, RT-PCR, and other molecular biological approaches in mast cells.


RESULTS
We screened approximately 100 natural plant extracts collected in Korea for in vitro anti-allergic activity. The leaf extract of Camellia japonica (LECJ) exhibited the most potent effect on degranulation in antigen-stimulated rodent and human mast cells. LECJ reversibly inhibited degranulation in a dose-dependent manner, with IC(50) values of approximately 50 microg/mL for the mast cells, and it also suppressed the expression and secretion of TNF-alpha and IL-4 in rat basophilic leukaemia-2H3 mast cells. In agreement with its in vitro activity, LECJ significantly inhibited mast cell-mediated PCA in an animal model. LECJ inhibited activating phosphorylation of tyrosine Y371 on Syk kinase, indicating that LECJ inhibits the activity of Src-family kinases in mast cells. In the in vitro kinase assay, LECJ directly inhibited Lyn kinase, the major Src-family kinase in the cells. It also suppressed Akt and MAP kinases, which are critical for the production of various pro-inflammatory cytokines in mast cells. In high-performance liquid chromatography analysis, quercetin-3-beta-D-glucoside and eugenol were identified as the major active components.


CONCLUSIONS
The present results strongly suggest that the anti-allergic activity of LECJ is mediated through inhibiting degranulation and allergic cytokine secretion by inhibition of Src-family kinase in mast cells and it may be useful for the treatment of mast cell-related immediate and delayed allergic diseases.
Lee
J-H
JH
Department of Immunology and Physiology, College of Medicine, Konkuk University, Chungju, Korea.
Kim
J-W
JW
Ko
N-Y
NY
Mun
S-H
SH
Kim
D-K
DK
Kim
J-D
JD
Kim
H-S
HS
Lee
K-R
KR
Kim
Y-K
YK
Radinger
M
M
Her
E
E
Choi
W-S
WS
D000818:Animals; D001491:Basophils; D028244:Camellia / Q000737:chemistry*; D015550:Cell Degranulation; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D006969:Hypersensitivity, Immediate / Q000188:drug therapy; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000276:immunology; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D007723:Korea; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D010323:Passive Cutaneous Anaphylaxis; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D047908:Intracellular Signaling Peptides and Proteins; D010936:Plant Extracts; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C000606898:Syk protein, rat; D019061:src-Family Kinases