Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy

Zhu,Xueyi; Cao,Yuxue; Su,Mingyue; Chen,Mengmeng; Li,Congcong; Yi,La; Qin,Jingjing; Tulake,Wuniqiemu; Teng,Fangzhou; Zhong,Yuanyuan; Tang,Weifeng; Wang,Shiyuan; Dong,Jingcheng

doi:10.3892/mmr.2021.12445

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy

Authors:
- Xueyi Zhu
- Yuxue Cao
- Mingyue Su
- Mengmeng Chen
- Congcong Li
- La Yi
- Jingjing Qin
- Wuniqiemu Tulake
- Fangzhou Teng
- Yuanyuan Zhong
- Weifeng Tang
- Shiyuan Wang
- Jingcheng Dong
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Affiliations: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Pulmonary Diseases and Oncology, Pu'er Hospital of Traditional Chinese Medicine, Kunming, Yunnan 665000, P.R. China
Published online on: September 17, 2021 https://doi.org/10.3892/mmr.2021.12445
Article Number: 805
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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