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<p>Idiopathic pulmonary fibrosis (IPF) represents a chronic, non-reversible, and irreversible interstitial lung disease with the lack of curative interventions and a poor prognosis; identifying safe and effective therapeutic agents is of paramount importance. The Ophiopogon-Ginseng herb pair, a classical traditional Chinese medicine (TCM), exerts Qi-replenishing and Yin-nourishing effects. Its active constituents Ophiopogonin D (OP-D), Ginsenoside Rg1 (Rg1), and Ginsenoside Rg3 (Rg3) have individual anti-fibrotic potential, while their synergistic effects in IPF remain to be elucidated. This study aimed to explore how OP-D-Rg1-Rg3 attenuates IPF and to clarify its possible molecular mechanisms. Bleomycin (BLM)-induced cellular senescence and transforming growth factor-β1 (TGF-β1) induce epithelial-mesenchymal transition (EMT) in A549 cells. MTT assay and RSM determined the optimal combination ratio. Cellular senescence and EMT were assessed by SA-β-Gal staining, RT-qPCR, WB, and ELISA. An IPF mouse model was established by intratracheal BLM administration, followed by treatment with the optimized OP-D-Rg1-Rg3 combination, pirfenidone (PFD), or saline for 21&#xa0;days. Pulmonary structural alterations and molecular changes were then evaluated by micro-CT, HE, Masson, and molecular analyses. The results showed that the synergistic OP-D-Rg1-Rg3 combination markedly attenuated A549 cell senescence, as evidenced by reduced SA-β-Gal activity and decreased expression of p53, p21, p16, and TGF-β1-induced EMT (upregulated E-cadherin, downregulated vimentin, fibronectin, Col-I). In vivo, the combination alleviated AEC2s senescence and pulmonary EMT, improved mouse body weight and lung morphology, reduced histopathological damage, and attenuated IPF. In conclusion, the OP-D-Rg1-Rg3 combination ameliorates IPF by inhibiting AEC2s senescence and EMT, highlighting promising clinical application prospects for IPF treatment.</p>

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Combination of Ophiopogonin D, Ginsenoside Rg1, and Ginsenoside Rg3 ameliorates idiopathic pulmonary fibrosis via inhibiting type 2 alveolar epithelial cell senescence and epithelial-mesenchymal transition

  • 期刊论文

  • 发表日期：

    2026年5月4日

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  • Jiang Zhu,
  • Kai Gong,
  • Mengzhen Xu,
  • Tianying Sun,
  • Zhiyang Li,
  • Yan Liu,
  • Lingyu Li,
  • Li Xiao,
  • Chuanguo Liu,
  • Qingjun Zhu

摘要

Idiopathic pulmonary fibrosis (IPF) represents a chronic, non-reversible, and irreversible interstitial lung disease with the lack of curative interventions and a poor prognosis; identifying safe and effective therapeutic agents is of paramount importance. The Ophiopogon-Ginseng herb pair, a classical traditional Chinese medicine (TCM), exerts Qi-replenishing and Yin-nourishing effects. Its active constituents Ophiopogonin D (OP-D), Ginsenoside Rg1 (Rg1), and Ginsenoside Rg3 (Rg3) have individual anti-fibrotic potential, while their synergistic effects in IPF remain to be elucidated. This study aimed to explore how OP-D-Rg1-Rg3 attenuates IPF and to clarify its possible molecular mechanisms. Bleomycin (BLM)-induced cellular senescence and transforming growth factor-β1 (TGF-β1) induce epithelial-mesenchymal transition (EMT) in A549 cells. MTT assay and RSM determined the optimal combination ratio. Cellular senescence and EMT were assessed by SA-β-Gal staining, RT-qPCR, WB, and ELISA. An IPF mouse model was established by intratracheal BLM administration, followed by treatment with the optimized OP-D-Rg1-Rg3 combination, pirfenidone (PFD), or saline for 21 days. Pulmonary structural alterations and molecular changes were then evaluated by micro-CT, HE, Masson, and molecular analyses. The results showed that the synergistic OP-D-Rg1-Rg3 combination markedly attenuated A549 cell senescence, as evidenced by reduced SA-β-Gal activity and decreased expression of p53, p21, p16, and TGF-β1-induced EMT (upregulated E-cadherin, downregulated vimentin, fibronectin, Col-I). In vivo, the combination alleviated AEC2s senescence and pulmonary EMT, improved mouse body weight and lung morphology, reduced histopathological damage, and attenuated IPF. In conclusion, the OP-D-Rg1-Rg3 combination ameliorates IPF by inhibiting AEC2s senescence and EMT, highlighting promising clinical application prospects for IPF treatment.