Wang Ruizhi, Xiao Zhenhao, Shi Xunqing, Ye Fan, Chen Junhai, Dong Min, Qiu Huijun, Zhang Yana, Shi Jianbo, Zhou Min, Yang Qintai
Department of Otolaryngology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China; Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China; Key Laboratory of Airway Inflammatory Disease Research and Innovative Technology Translation, Guangzhou, 510630, China.
Maoming Hospital Affiliated to Guangzhou University of Chinese Medicine, Maoming, 525000, China.
J Ethnopharmacol. 2025 May 28;348:119789. doi: 10.1016/j.jep.2025.119789. Epub 2025 Apr 12.
Xiaoqinglong Decoction combined with Yupingfeng Powder (XQLDwYPFP) is widely used to treat allergic rhinitis and bronchial asthma in Traditional Chinese Medicine, while its efficacy and mechanisms in combined allergic rhinitis and asthma syndrome (CARAS) remain underexplored.
To elucidate the mechanisms and pharmacodynamic basis of XQLDwYPFP in CARAS treatment.
A CARAS mouse model was established using ovalbumin (OVA). Airway allergic symptoms were assessed by recording nasal rubbing and sneezing frequencies. Serum OVA-sIgE levels were measured via ELISA. Histopathological changes were evaluated using HE, PAS, and C2R staining. Flow cytometry quantified Th cell subsets. Proteomics identified differential protein expression with GO and KEGG databases used for pathway enrichment analysis. Immunofluorescence assessed B lymphocyte activation, while Western blot and immunohistochemistry evaluated JAK1/JAK2-STAT1 pathway activation. Molecular docking validated the binding affinity of XQLDwYPFP components to JAK2 and STAT1.
XQLDwYPFP alleviated airway symptoms, reduced serum OVA-sIgE, and inhibited goblet cell hyperplasia and eosinophil infiltration in nasal and lung tissues. It decreased Th2 cell proportions and increased the Th1/Th2 ratio in lung and spleen tissues. Proteomics revealed that XQLDwYPFP suppresses CARAS by targeting the MHC II-mediated antigen presentation pathway. The formula reduced activated B lymphocytes and downregulated JAK2, p-JAK2, STAT1, and p-STAT1 expression in nasal and lung tissues. XQLDwYPFP representative components exhibited strong binding affinity to JAK2 and STAT1.
XQLDwYPFP alleviates type 2 inflammation in CARAS by regulating the JAK2-STAT1-MHC II pathway and inhibiting B lymphocyte-mediated antigen presentation. These findings provide novel pharmacological evidence supporting its clinical use for CARAS.
在传统中医中，小青龙汤合玉屏风散广泛用于治疗过敏性鼻炎和支气管哮喘，但其在合并过敏性鼻炎和哮喘综合征（CARAS）中的疗效及机制仍未得到充分研究。
阐明小青龙汤合玉屏风散治疗CARAS的机制及药效学基础。
用卵清蛋白（OVA）建立CARAS小鼠模型。通过记录鼻擦和喷嚏频率评估气道过敏症状。采用酶联免疫吸附测定法检测血清OVA特异性免疫球蛋白E（OVA-sIgE）水平。用苏木精-伊红（HE）、过碘酸-雪夫（PAS）和C2R染色评估组织病理学变化。流式细胞术定量分析Th细胞亚群。蛋白质组学鉴定差异蛋白表达，并使用基因本体（GO）和京都基因与基因组百科全书（KEGG）数据库进行通路富集分析。免疫荧光评估B淋巴细胞活化，而蛋白质免疫印迹法和免疫组织化学评估JAK1/JAK2-信号转导和转录激活因子1（STAT1）通路的活化。分子对接验证小青龙汤合玉屏风散成分与JAK2和STAT1的结合亲和力。
小青龙汤合玉屏风散减轻气道症状，降低血清OVA-sIgE水平，并抑制鼻和肺组织中杯状细胞增生和嗜酸性粒细胞浸润。它降低了肺和脾组织中Th2细胞比例，提高了Th1/Th2比值。蛋白质组学显示，小青龙汤合玉屏风散通过靶向主要组织相容性复合体II（MHC II）介导的抗原呈递途径抑制CARAS。该方剂减少了活化的B淋巴细胞，并下调了鼻和肺组织中JAK2、磷酸化JAK2（p-JAK2）、STAT1和磷酸化STAT1（p-STAT1）的表达。小青龙汤合玉屏风散代表性成分对JAK2和STAT1表现出较强的结合亲和力。
小青龙汤合玉屏风散通过调节JAK2-STAT1-MHC II通路并抑制B淋巴细胞介导的抗原呈递，减轻CARAS中的2型炎症。这些发现为其在CARAS临床应用中提供了新的药理学证据。
