Background

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with limited therapeutic strategies. Therefore, there is an urgent need to search for safe and effective drugs to treat this condition. Ophiopogonin D (OP-D), a steroidal saponin compound extracted from ophiopogon, possesses various pharmacological properties, including anti-inflammatory, antioxidant, and antitumor effects. However, the potential pharmacological effect of OP-D on pulmonary fibrosis remains unknown.

Purpose

The aim of this study was to investigate whether OP-D can improve pulmonary fibrosis and to explore its mechanism of action.

Methods

The effect of OP-D on pulmonary fibrosis was investigated in vitro and in vivo using a mouse model of IPF induced by bleomycin and an in vitro model of human embryonic lung fibroblasts induced by transforming growth factor-β1 (TGF-β1). The mechanism of action of OP-D was determined using multi-omics techniques and bioinformatics.

Results

OP-D attenuated epithelial-mesenchymal transition and excessive deposition of extracellular matrix in the lungs, promoted the apoptosis of lung fibroblasts, and blocked the differentiation of lung fibroblasts into myofibroblasts. The multi-omics techniques and bioinformatics analysis revealed that OP-D blocked the AKT/GSK3β pathway, and the combination of a PI3K/AKT inhibitor and OP-D was effective in alleviating pulmonary fibrosis.

Conclusion

This study demonstrated for the first time that OP-D can reduce lung inflammation and fibrosis. OP-D is thus a potential new drug for the prevention and treatment of pulmonary fibrosis.

中文翻译：

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多组学分析揭示麦冬皂苷D抗肺纤维化作用机制

背景

特发性肺纤维化（IPF）是一种慢性进行性肺部疾病，治疗策略有限。因此，迫切需要寻找安全有效的药物来治疗这种疾病。麦冬素 D (OP-D) 是一种从麦冬中提取的甾体皂苷化合物，具有多种药理特性，包括抗炎、抗氧化和抗肿瘤作用。然而，OP-D 对肺纤维化的潜在药理作用仍不清楚。

目的

本研究旨在探讨OP-D能否改善肺纤维化并探讨其作用机制。

方法

使用博莱霉素诱导的IPF小鼠模型和转化生长因子-β1（TGF-β1）诱导的人胚胎肺成纤维细胞体外模型，在体外和体内研究了OP -D对肺纤维化的影响。使用多组学技术和生物信息学确定了 OP-D 的作用机制。

结果

OP-D减弱肺内上皮间质转化和细胞外基质过度沉积，促进肺成纤维细胞凋亡，并阻断肺成纤维细胞向肌成纤维细胞分化。多组学技术和生物信息学分析表明OP-D阻断AKT/GSK3β通路，PI3K/AKT抑制剂与OP-D联合可有效减轻肺纤维化。

结论

这项研究首次证明OP-D可以减轻肺部炎症和纤维化。因此OP-D是一种潜在的预防和治疗肺纤维化的新药。