Xinqin exhibits the anti-allergic effect through the JAK2/STAT5 signaling pathway.
BACKGROUND
Xinqin, a polyherbal medicine, is an important traditional Chinese herbal formula used in traditional oriental medicine for treatment of allergic rhinitis (AR). The formula is based on the Chinese Pharmacopoeia AIM OF THE STUDY: Previously, Xinqin exhibited potent anti-allergic effect in a guinea pig model of AR. In this study, we explored the molecular mechanism of the anti-allergic effect mediated by Xinqin.


METHODS
AR was induced in guinea pigs (Hartley) with toluene-2, 4-diisocyanate (TDI) in vivo and in HMC-1 mast cells with A23187/phorbol 12-myristate-13-acetate (PMA) in vitro. The releases of allergic inflammatory mediators such as histamine, leukotriene (LT) D4, immunoglobulin (Ig) E, TNF-α, and IL-6 were analyzed for allergy. The mast cell degranulation was displayed in HMC-1 mast cells. The activities of janus protein kinase 2 (JAK2), signal transduction and activator of transcription 5 (STAT5) and suppressor of cytokine signaling 3 (SOCS3) were evaluated by Western blot.


RESULTS
Treatment with Xinqin resulted in AR symptoms and decreases in levels of histamine, LTD4, IgE, TNF-α, and IL-6 in serum of guinea pig model of AR and in A23187/PMA-stimulated HMC-1 mast cells. Treatment with Xinqin also inhibited cell degranulation in A23187/PMA-stimulated HMC-1 mast cells. The JAK2/STAT5 signaling pathway could play an important role in the anti-allergic activity mediated by Xinqin.


CONCLUSIONS
Xinqin exerts the anti-allergic effect by modulating mast cell-mediated allergic responses by down-regulating JAK2/STAT5 signaling pathway. Results from this study provide a mechanistic basis for the application of Xinqin in the treatment of AR.
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Qian
Q
Zhang
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Ying
Y
Xiong
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Guo-Bing
GB
Li
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Qin
Q
Tang
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Min
M
Cao
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Jing-Bin
JB
Huang
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Mao
M
Xing
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Chang-Peng
CP
Hu
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Ya
Y
Gong
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Qing-Hua
QH
Wang
College of Pharmacy, Third Military Medical University, Chongqing, China. Electronic address: gaoning59@163.com.
Ning
N
Gao
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China. Electronic address: xqpharmacylab@126.com.
Rong
R
Zhang
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000097:blood; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D053614:Janus Kinase 2 / Q000378:metabolism*; D017998:Leukotriene D4 / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D065631:Rhinitis, Allergic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014051:Toluene 2,4-Diisocyanate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018926:Anti-Allergic Agents; D004365:Drugs, Chinese Herbal; C508600:IL6 protein, human; D015850:Interleukin-6; C106644:SOCS3 protein, human; D050799:STAT5 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D014409:Tumor Necrosis Factor-alpha; C000617119:xinqin; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E; D000001:Calcimycin; D017998:Leukotriene D4; D006632:Histamine; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D013755:Tetradecanoylphorbol Acetate
Allergic rhinitis; Anti-allergic effect; JAK2/STAT5 pathway; Xinqin