Abstract

Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from Dipsacus asper Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200 μΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) (1 mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300 mg/kg) or AICAR (100 mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation.

中文翻译：

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木通皂苷 D 通过 AMPK 激活减轻过敏性气道炎症

摘要

Akebia saponin D (ASD) 是从续断中提取的具有生物活性的三萜皂苷。ex DC.. 本研究旨在调查 ASD 对过敏性气道炎症的影响。用ASD（50、100和200μM）和AMPK激活剂5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核苷（AICAR）预处理人肺上皮BEAS-2B细胞和骨髓源性肥大细胞（BMMC） (1 mM)，然后用脂多糖 (LPS) 或 IL-33 刺激。ASD 和 AICAR 预处理显着抑制 BEAS-2B 细胞产生 TNF-α 和 IL-6，以及 BMMC 产生 IL-13。此外，ASD 和 AICAR 预处理显着增加了 BEAS-2B 细胞中 p-AMPK 的表达。siRNA 和化合物 C 对 AMPK 的抑制部分消除了 ASD 对 TNF-α、IL-6 和 IL-13 产生的抑制作用。通过卵清蛋白 (OVA) 激发诱导哮喘小鼠模型，并用 ASD（150 和 300 mg/kg）或 AICAR（100 mg/kg）治疗。在 ASD 和 AICAR 治疗的小鼠中，嗜酸性粒细胞、中性粒细胞、单核细胞和淋巴细胞的浸润以及 TNF-α、IL-6、IL-4 和 IL-13 的产生均减弱。ASD 和 AICAR 治疗后，肺部组织病理学变化也得到改善。此外，它表明 ASD 和 AICAR 治疗增加了肺组织中 p-AMPK 的表达。总之，ASD 通过诱导 AMPK 激活对过敏性气道炎症表现出保护作用。