Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Institutes of Integrative Medicine, Fudan University, Shanghai, China.
Oxid Med Cell Longev. 2022 Oct 25;2022:6842530. doi: 10.1155/2022/6842530. eCollection 2022.
Cycloastragenol (CAG) has been reported to alleviate airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. However, its specific mechanisms remain unclear.
This study is aimed at investigating the effects of CAG on asthma, comparing its efficacy with dexamethasone (DEX), and elucidating the mechanism of CAG's regulation.
The asthma mouse model was induced by OVA. CAG at the optimal dose of 125 mg/kg was given every day from day 0 for 20-day prevention or from day 14 for a 7-day treatment. We observed the preventive and therapeutic effects of CAG in asthmatic mice by evaluating the airway inflammation, AHR, and mucus secretion. Lung proteins were used for TMT-based quantitative proteomic analysis to enunciate its regulatory mechanisms.
The early administration of 125 mg/kg CAG before asthma happened prevented asthmatic mice from AHR, airway inflammation, and mucus hypersecretion, returning to nearly the original baseline. Alternatively, the administration of CAG during asthma also had the same therapeutic effects as DEX. The proteomic analysis revealed that the therapeutical effects of CAG were associated with 248 differentially expressed proteins and 3 enriched KEGG pathways. We then focused on 3 differentially expressed proteins (ITGAL, Syk, and Vav1) and demonstrated that CAG treatment downregulated ITGAL, Syk, and Vav1 by quantitative real-time PCR, western blot analysis, and immunohistochemical staining.
These findings suggest that CAG exerts preventive and protective effects on asthma by inhibiting ITGAL, Syk, and the downstream target Vav1.
环黄芪醇（CAG）已被报道可减轻卵清蛋白（OVA）诱导的哮喘小鼠的气道炎症。然而，其具体机制尚不清楚。
本研究旨在研究 CAG 对哮喘的影响，比较其与地塞米松（DEX）的疗效，并阐明 CAG 调节的机制。
通过 OVA 诱导哮喘小鼠模型。从第 0 天开始，每天给予最佳剂量 125mg/kg 的 CAG 进行 20 天预防或从第 14 天开始进行 7 天治疗。通过评估气道炎症、AHR 和黏液分泌，观察 CAG 在哮喘小鼠中的预防和治疗作用。肺蛋白用于基于 TMT 的定量蛋白质组学分析，以阐明其调节机制。
在哮喘发生前早期给予 125mg/kg CAG 可预防哮喘小鼠发生 AHR、气道炎症和黏液高分泌，使其几乎恢复到原始基线水平。相反，在哮喘期间给予 CAG 也具有与 DEX 相同的治疗作用。蛋白质组学分析表明，CAG 的治疗作用与 248 个差异表达蛋白和 3 个富集的 KEGG 途径有关。然后，我们重点关注 3 个差异表达蛋白（ITGAL、Syk 和 Vav1），并通过定量实时 PCR、western blot 分析和免疫组织化学染色证实 CAG 处理下调了 ITGAL、Syk 和 Vav1。
这些发现表明，CAG 通过抑制 ITGAL、Syk 和下游靶标 Vav1 对哮喘发挥预防和保护作用。
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