Mast cell-mediated allergic response is suppressed by Sophorae flos: inhibition of SRC-family kinase.
Complementary and alternative medicines are considered as a promising direction for the development of anti-allergic therapies in oriental countries. We screened approximately 100 oriental herbal medicines for anti-allergic activity. Sophorae flos exhibited the most potent effect on degranulation in antigen-stimulated mast cells. We further investigated the effect of Sophorae flos on the IgE-mediated allergic response in vivo and its mechanism of action in mast cells. Sophorae flos exhibited a significant inhibitory effect on degranulation in antigen-stimulated mast cells with IC(50) values of approximately 31.6 microg/mL (RBL-2H3 mast cells) and approximately 47.8 microg/mL (bone marrow-derived mast cells). Sophorae flos also suppressed the expression and secretion of TNF-alpha and IL-4 in the cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Sophorae flos inhibited the activating phosphorylation of Syk and LAT in mast cells. Further downstream, activating phosphorylation of Akt and the prototypic MAP kinases, namely, p38, ERK1/2, and JNK, were also inhibited. These results suggest that Sophorae flos inhibits the Src family kinase-dependent signaling cascades in mast cells and may thus exert anti-allergic activity.
Lee
Jun Ho
JH
Department of Immunology, College of Medicine, Konkuk University, Chungyu. Korea.
Kim
Jie Wan
JW
Ko
Na Young
NY
Mun
Se Hwan
SH
Kim
Do Kyun
DK
Kim
Ju Dong
JD
Won
Hyung Sik
HS
Shin
Hwa Sup
HS
Kim
Hyung Sik
HS
Her
Erk
E
Kim
Young Mi
YM
Choi
Wahn Soo
WS
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006967:Hypersensitivity / Q000188:drug therapy* / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D029909:Sophora; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000941:Antigens; D004365:Drugs, Chinese Herbal; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases