Liu L-L, Li F-H, Zhang Y, Zhang X-F, Yang J
Children's Medical Center, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Department of Pathology, Shandong University of Medicine, Jinan, Shandong, China.
Braz J Med Biol Res. 2017 Jul 20;50(8):e5991. doi: 10.1590/1414-431X20175991.
Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.
哮喘是一种慢性过敏性疾病，其特征为气道炎症、气道高反应性（AHR）和黏液分泌过多。T淋巴细胞参与哮喘的发病机制，通过分泌细胞因子介导气道炎症反应。磷酸肌醇3激酶（PI3K）和Notch信号通路与T细胞信号传导、增殖和分化相关，在哮喘进展中起重要作用。因此，能够调节T细胞增殖和功能的化合物可能具有临床价值。在此，我们评估了植物源黄酮类化合物橘皮素在实验性哮喘中的作用。对出生后第12天的BALB/c小鼠用卵清蛋白（OVA）进行激发。将小鼠分成不同组（每组n = 18），通过口服灌胃给予25或50 mg/kg体重的橘皮素。地塞米松用作阳性对照。橘皮素治疗减少了支气管肺泡灌洗液（BALF）中的炎性细胞浸润，还恢复了肺组织的正常组织学。血清和BALF中OVA特异性IgE水平降低。通过气道阻力和肺顺应性测定的AHR恢复正常。流式细胞术分析显示Th17细胞群体减少。橘皮素降低了Th2和Th17细胞因子水平并提高了IFN-γ水平。PI3K信号传导受到抑制。橘皮素下调了Notch 1受体及其配体Jagged 1和2的表达。我们的研究结果支持橘皮素可能用于治疗过敏性哮喘。
