15,16-Dihydrotanshinone I suppresses IgE-Ag stimulated mouse bone marrow-derived mast cell activation by inhibiting Syk kinase.
BACKGROUND
15,16-Dihydrotanshinone I (DHT-I), isolated from the dried root of Salvia miltiorrhiza Bung, which is traditionally used to treat cardiovascular and inflammatory diseases agent in Chinese medicine. DHT-I has been reported to have a broad range of biological activities, including antibacterial activity, and has been used to treat circulatory disorders, hepatitis, inflammation, cancer, and neurodegenerative diseases.


OBJECTIVE
The aim of this study was to evaluate the anti-allergic inflammatory effects of DHT-I on degranulation and on the generation of eicosanoids, such as, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4), in IgE/Ag-stimulated bone marrow-derived mast cells (BMMCs).


METHODS
The anti-allergic inflammatory activity of DHT-I was evaluated using BMMCs. The effects of DHT-I on mast cell activation were investigated by following degranulation and eicosanoid generation using ELISA and immunoblotting and immunoprecipitation techniques.


RESULTS
DHT-I at a concentration of 20μM markedly inhibited degranulation and the generation of PGD2 and LTC4 in IgE/Ag-stimulated BMMCs (about 90% inhibitions, respectively). Analyses of FcεRI-mediated signaling pathways demonstrated that DHT-I inhibited the phosphorylations of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT), and inhibited downstream signaling process, including [Ca(2+)]i mobilization induced by the phosphorylation of phospholipase Cγ1 (PLCγ1), and the activations of mitogen-activated protein kinases (MAPKs) and the Akt-nuclear factor-κB (NF-κB) pathway.


CONCLUSIONS
DHT-1 inhibits the release of allergic inflammatory mediators from IgE/Ag-stimulated mast cells by suppressing a FcεRI-mediated Syk-dependent signal pathway. This result suggests DHT-I offers a novel developmental basis for drugs targeting allergic inflammatory diseases.
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Xian
X
Li
Korea Medicine-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
Ju Hye
JH
Yang
Yanbian University Hospital, Yanji, Jilin Province, China.
Ye
Y
Jin
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Fansi
F
Jin
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Dong-Young
DY
Kim
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Jae-Hoon
JH
Chang
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Jung-Ae
JA
Kim
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Jong-Keun
JK
Son
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Tae Chul
TC
Moon
Department of Food Science and Nutrition, Andong National University, Andong 760-749, Republic of Korea. Electronic address: sonkh@andong.ac.kr.
Kun Ho
KH
Son
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: hwchang@yu.ac.kr.
Hyeun Wook
HW
Chang
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005663:Furans; D007073:Immunoglobulin E / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011809:Quinones; D027561:Salvia miltiorrhiza; D000072377:Syk Kinase
D005663:Furans; D047908:Intracellular Signaling Peptides and Proteins; D010616:Phenanthrenes; D011809:Quinones; D007073:Immunoglobulin E; C000713095:dihydrotanshinone I; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse
15,16-Dihydrotanshinone I; Allergic inflammation; Bone marrow-derived mast cells; Leukotriene C(4); Prostaglandin D(2); Spleen tyrosine kinase