Phytomedicine ( IF 6.7 ) Pub Date : 2023-09-14 , DOI: 10.1016/j.phymed.2023.155078 Shengchuan Bao 1 , Ting Chen 1 , Juan Chen 1 , Jiaxiang Zhang 1 , Guangjian Zhang 2 , Yi Hui 1 , Jingtao Li 3 , Shuguang Yan 1
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:
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。