Multi-omics analysis reveals the mechanism of action of ophiopogonin D against pulmonary fibrosis

  • Phytomedicine. 2023 Dec:121:155078. 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  4
Affiliations
  • 1. College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China; Key Laboratory of Gastrointestinal Diseases and Prescriptions in Shaanxi Province, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
  • 2. Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
  • 3. Key Laboratory of Gastrointestinal Diseases and Prescriptions in Shaanxi Province, Shaanxi University of Chinese Medicine, Xianyang 712046, China; Departments of Infectious Disease, The Affliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, China. Electronic address: [email protected].
  • 4. College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China; Key Laboratory of Gastrointestinal Diseases and Prescriptions in Shaanxi Province, Shaanxi University of Chinese Medicine, Xianyang 712046, China. Electronic address: [email protected].
PMID: 37734252 DOI: 10.1016/j.phymed.2023.155078
Abstract

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.

Keywords
AKT/GSK3β pathway; Bleomycin; Epithelial–mesenchymal transition; Extracellular matrix; Idiopathic pulmonary fibrosis; Ophiopogonin D.
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