Zhang Qian, Xiong Ying, Li Guo-Bing, Tang Qin, Cao Min, Huang Jing-Bin, Xing Mao, Hu Chang-Peng, Gong Ya, Wang Qing-Hua, Gao Ning, Zhang Rong
Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
College of Pharmacy, Third Military Medical University, Chongqing, China.
J Ethnopharmacol. 2016 Dec 4;193:466-473. doi: 10.1016/j.jep.2016.09.045. Epub 2016 Sep 23.
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.
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.
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.
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.
辛芩是一种多草药制剂，是传统东方医学中用于治疗过敏性鼻炎（AR）的重要传统中药配方。该配方以《中国药典》为依据。研究目的：此前，辛芩在AR豚鼠模型中表现出强大的抗过敏作用。在本研究中，我们探讨了辛芩介导的抗过敏作用的分子机制。
在体内用甲苯-2,4-二异氰酸酯（TDI）诱导豚鼠（Hartley）发生AR，在体外用人肥大细胞白血病细胞系（HMC-1）肥大细胞用A23187/佛波醇12-肉豆蔻酸酯-13-乙酸酯（PMA）诱导AR。分析组胺、白三烯（LT）D4、免疫球蛋白（Ig）E、肿瘤坏死因子-α（TNF-α）和白细胞介素-6等过敏性炎症介质的释放情况以评估过敏反应。在HMC-1肥大细胞中观察肥大细胞脱颗粒情况。通过蛋白质免疫印迹法评估酪氨酸激酶2（JAK2）、信号转导及转录激活因子5（STAT5）和细胞因子信号转导抑制因子3（SOCS3）的活性。
辛芩治疗可减轻AR豚鼠模型血清以及A23187/PMA刺激的HMC-1肥大细胞中AR症状，并降低组胺、白三烯D4、IgE、TNF-α和IL-6的水平。辛芩治疗还可抑制A23187/PMA刺激的HMC-1肥大细胞的细胞脱颗粒。JAK2/STAT5信号通路可能在辛芩介导的抗过敏活性中起重要作用。
辛芩通过下调JAK2/STAT5信号通路调节肥大细胞介导的过敏反应，从而发挥抗过敏作用。本研究结果为辛芩在AR治疗中的应用提供了机制依据。
