Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China.
Department of Pulmonary and Critical Care Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
J Biochem Mol Toxicol. 2022 Aug;36(8):e23084. doi: 10.1002/jbt.23084. Epub 2022 Apr 28.
Dioscin is a natural product that possesses protective effects on multiple chronic injuries, but its effects on asthma are not fully understood. Herein, we evaluated its effects on asthmatic mice established by ovalbumin (OVA) sensitization and challenges and further explored the mechanism. Inflammatory cells in bronchoalveolar lavage fluids (BALFs) were analyzed using Diff-Quik staining. OVA-specific immunoglobulin E (IgE)/IgG1 in serum and inflammatory cytokines (interleukin 4[IL-4], IL-5, IL-13, and tumor necrosis factor-α) in BALFs and lung tissues were measured using Enzyme-Linked Immunosorbent Assay Kits. Hematoxylin and eosin, periodic acid-Schiff, and immunohistochemistry staining showed histopathological changes in lung tissues. Epithelial-mesenchymal transition (EMT) in human bronchial epithelial (16HBE) cells was assessed by immunofluorescence staining. Hydroxyproline content was used to evaluate collagen deposition. Polymerase chain reaction and Western blot were performed to measure messenger RNA and protein expression. We found that dioscin treatment (particularly at the dose of 80 mg/kg) significantly inhibited pulmonary inflammation in asthmatic mice, as evidenced by the decreased serum OVA-specific IgE/IgG1 and the reduced inflammatory cells and cytokines in BALFs and lung tissues. Moreover, dioscin effectively ameliorated the goblet cell hyperplasia, mucus hypersecretion, collagen deposition, and smooth muscle hyperplasia in the airways of asthmatic mice. Mechanistically, dioscin restrained the activated TGF-β1/Smad2/3 and protein kinase B (AKT) signal pathways in lung tissues and potently reversed the TGF-β1-induced EMT and phosphorylation of Smad2/3 and AKT in 16HBE cells. Collectively, dioscin displayed protective effects on OVA-induced asthmatic mice via adjusting TGF-β1/Smad2/3 and AKT signal pathways, supporting the fact that dioscin could be a candidate for chronic asthma prevention in the future.
薯蓣皂苷是一种天然产物，对多种慢性损伤具有保护作用，但对哮喘的作用尚不完全清楚。在此，我们评估了其对卵清蛋白（OVA）致敏和激发建立的哮喘小鼠的作用，并进一步探讨了其机制。用 Diff-Quik 染色分析支气管肺泡灌洗液（BALF）中的炎性细胞。用酶联免疫吸附测定试剂盒检测血清中 OVA 特异性免疫球蛋白 E（IgE）/IgG1 和 BALF 和肺组织中的炎症细胞因子（白细胞介素 4[IL-4]、IL-5、IL-13 和肿瘤坏死因子-α）。苏木精和伊红、过碘酸希夫和免疫组织化学染色显示肺组织的组织病理学变化。用免疫荧光染色评估人支气管上皮（16HBE）细胞中的上皮-间充质转化（EMT）。用羟脯氨酸含量评估胶原蛋白沉积。进行聚合酶链反应和 Western blot 以测量信使 RNA 和蛋白表达。我们发现薯蓣皂苷治疗（特别是 80mg/kg 剂量）显著抑制哮喘小鼠的肺部炎症，这表现在血清 OVA 特异性 IgE/IgG1 降低，BALF 和肺组织中的炎症细胞和细胞因子减少。此外，薯蓣皂苷有效改善哮喘小鼠气道中的杯状细胞增生、黏液高分泌、胶原沉积和平滑肌增生。在机制上，薯蓣皂苷在肺组织中抑制激活的 TGF-β1/Smad2/3 和蛋白激酶 B（AKT）信号通路，并在 16HBE 细胞中有力地逆转 TGF-β1 诱导的 EMT 和 Smad2/3 和 AKT 的磷酸化。总之，薯蓣皂苷通过调节 TGF-β1/Smad2/3 和 AKT 信号通路对 OVA 诱导的哮喘小鼠显示出保护作用，支持薯蓣皂苷将来可能成为慢性哮喘预防的候选药物。
