ophiopogonin-d and Idiopathic-Pulmonary-Fibrosis

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.

Topics: Animals; Bleomycin; Fibroblasts; Humans; Idiopathic Pulmonary Fibrosis; Lung; Mice; Mice, Inbred C57BL; Multiomics; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Saponins; Transforming Growth Factor beta1