特发性肺纤维化（IPF）是一种慢性进行性肺部疾病，治疗方法有限。因此，迫切需要寻找安全有效的药物来治疗这种病症。蛇床子苷D（OP-D）是从蛇床子中提取的一种甾体皂苷化合物，具有多种药理学特性，包括抗炎、抗氧化和抗肿瘤作用。然而，OP-D在治疗肺纤维化方面的潜在药理作用尚不清楚。 本研究的目的是研究OP-D是否可以改善肺纤维化，并探讨其机制。通过使用由博莱霉素诱导的IPF小鼠模型和由转化生长因子-β1（TGF-β1）诱导的人类胚胎肺成纤维细胞体外模型，在体内和体外研究了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。 OP-D减轻了肺部上皮间质转化和过度胞外基质沉积，促进了肺成纤维细胞的凋亡，并阻塞了肺成纤维细胞向肌成纤维细胞的分化。多组学技术和生物信息学分析揭示，OP-D阻断了AKT/GSK3β途径，并且PI3K/AKT抑制剂与OP-D的联合应用对缓解肺纤维化有效。 该研究首次证明了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物。 版权所有 © 2023 作者。Elsevier GmbH. 发表。保留所有权利。

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.The aim of this study was to investigate whether OP-D can improve pulmonary fibrosis and to explore its mechanism of action.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.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.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.Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.