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Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy.
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2021-09-20 , DOI: 10.3892/mmr.2021.12445
Xueyi Zhu 1 , Yuxue Cao 1 , Mingyue Su 2 , Mengmeng Chen 1 , Congcong Li 1 , La Yi 1 , Jingjing Qin 1 , Wuniqiemu Tulake 1 , Fangzhou Teng 1 , Yuanyuan Zhong 1 , Weifeng Tang 1 , Shiyuan Wang 1 , Jingcheng Dong 1
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Cycloastragenol (CAG), a secondary metabolite from the roots of Astragalus zahlbruckneri, has been reported to exert anti‑inflammatory effects in heart, skin and liver diseases. However, its role in asthma remains unclear. The present study aimed to investigate the effect of CAG on airway inflammation in an ovalbumin (OVA)‑induced mouse asthma model. The current study evaluated the lung function and levels of inflammation and autophagy via measurement of airway hyperresponsiveness (AHR), lung histology examination, inflammatory cytokine measurement and western blotting, amongst other techniques. The results demonstrated that CAG attenuated OVA‑induced AHR in vivo. In addition, the total number of leukocytes and eosinophils, as well as the secretion of inflammatory cytokines, including interleukin (IL)‑5, IL‑13 and immunoglobulin E were diminished in bronchoalveolar lavage fluid of the OVA‑induced murine asthma model. Histological analysis revealed that CAG suppressed inflammatory cell infiltration and goblet cell secretion. Notably, based on molecular docking simulation, CAG was demonstrated to bind to the active site of autophagy‑related gene 4‑microtubule‑associated proteins light chain 3 complex, which explains the reduced autophagic flux in asthma caused by CAG. The expression levels of proteins associated with autophagy pathways were inhibited following treatment with CAG. Taken together, the results of the present study suggest that CAG exerts an anti‑inflammatory effect in asthma, and its role may be associated with the inhibition of autophagy in lung cells.

中文翻译:

Cycloastragenol 通过抑制自噬减轻哮喘小鼠的气道炎症。

环黄芪素 (CAG) 是黄芪根部的一种次生代谢物,据报道对心脏、皮肤和肝脏疾病具有抗炎作用。然而,它在哮喘中的作用仍不清楚。本研究旨在研究 CAG 对卵白蛋白 (OVA) 诱导的小鼠哮喘模型气道炎症的影响。目前的研究通过测量气道高反应性 (AHR)、肺组织学检查、炎性细胞因子测量和蛋白质印迹等技术来评估肺功能和炎症和自噬水平。结果表明,CAG在体内减弱了 OVA 诱导的 AHR. 此外,在 OVA 诱导的小鼠哮喘模型的支气管肺泡灌洗液中,白细胞和嗜酸性粒细胞的总数以及炎性细胞因子(包括白细胞介素 (IL)-5、IL-13 和免疫球蛋白 E)的分泌减少。组织学分析显示,CAG 抑制炎症细胞浸润和杯状细胞分泌。值得注意的是,基于分子对接模拟,CAG 被证明与自噬相关基因 4 微管相关蛋白轻链 3 复合物的活性位点结合,这解释了 CAG 引起的哮喘自噬通量减少。用 CAG 处理后,与自噬途径相关的蛋白质的表达水平受到抑制。综上所述,本研究结果表明 CAG 在哮喘中发挥抗炎作用,
更新日期:2021-09-20
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