Lu Yuan, Xing Qiong-Qiong, Xu Jian-Ya, Ding Dou, Zhao Xia
Pediatric institution of Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, 210023, China.
Pediatric institution of Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing, 210023, China.
Int J Biol Macromol. 2016 Dec;93(Pt A):995-1006. doi: 10.1016/j.ijbiomac.2016.09.058. Epub 2016 Sep 16.
Endoplasmic reticulum (ER) stress has been recently revealed to play a pivotal role in the pathogenesis of severe asthma. Astragalus polysaccharide (APS), a major bioactive component from Astragalus membranaceus, exerts immunomodulatory and anti-inflammatory effects and has been shown to suppress ER stress in chronic diseases such as type-2 diabetes. However, the pharmaceutical application of APS in the treatment of severe asthma is unknown. The results obtained here indicate that APS significantly attenuates eosinophils and neutrophil-dominant airway inflammation by reducing the mRNA levels of Cxcl5, Il8, and chemokine (C-C motif) ligand 20 (Ccl20) and the protein levels of IL13RA and IL17RA. APS also inhibits the activation of unfolded protein response by decreasing the levels of ER stress markers such as C/EBP homologous protein (CHOP), which was associated with a reduction of PERK phosphorylation. Moreover, APS substantially blocks the nuclear translocation of ATF6 and NF-κB p65. Interestingly, we observed that APS markedly suppresses mucus hypersecretion by decreasing the levels of mucin (MUC) 5AC and MUC5B, which might be due to inhibition of goblet cells differentiation by suppressing the expression of IRE1β-correlated genes. In summary, APS can have potential pharmaceutical application in treatment of severe asthma.
内质网（ER）应激最近被揭示在重度哮喘的发病机制中起关键作用。黄芪多糖（APS）是黄芪的主要生物活性成分，具有免疫调节和抗炎作用，并且已被证明在2型糖尿病等慢性疾病中可抑制内质网应激。然而，APS在重度哮喘治疗中的药物应用尚不清楚。此处获得的结果表明，APS通过降低Cxcl5、Il8和趋化因子（C-C基序）配体20（Ccl20）的mRNA水平以及IL13RA和IL17RA的蛋白水平，显著减轻嗜酸性粒细胞和中性粒细胞为主的气道炎症。APS还通过降低内质网应激标志物如C/EBP同源蛋白（CHOP）的水平来抑制未折叠蛋白反应的激活，这与PERK磷酸化的减少有关。此外，APS基本上阻断了ATF6和NF-κB p65的核转位。有趣的是，我们观察到APS通过降低粘蛋白（MUC）5AC和MUC5B的水平显著抑制黏液高分泌，这可能是由于通过抑制IRE1β相关基因的表达来抑制杯状细胞分化所致。总之，APS在重度哮喘治疗中可能具有潜在的药物应用价值。
