Bryodulcosigenin attenuates bleomycin‐induced pulmonary fibrosis via inhibiting AMPK‐mediated mesenchymal epithelial transition and oxidative stress

Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in several organs, including the lungs. Bryodulcosigenin (BDG) is a cucurbitane‐type triterpene isolated from Siratia grosvenori and has clear‐cut anti‐inflammatory effects, yet its benefit of pulmonary...

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Published in:Phytotherapy research 2022-10, Vol.36 (10), p.3911-3923
Main Authors: Ding, Yue, Wang, Lei, Liu, Bei, Ren, Guoqing, Okubo, Ryosuke, Yu, Jing, Zhang, Chaofeng
Format: Article
Language:English
Subjects:
Alveoli
AMPK activation
Bleomycin
bryodulcosigenin
Collagen
epithelial–mesenchymal transition
Fibrosis
Histopathology
Inflammation
Lung diseases
Mesenchyme
Molecular docking
NOX4 protein
Oxidative stress
Pulmonary fibrosis
SIRT1 protein
Smad2 protein
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Summary:Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in several organs, including the lungs. Bryodulcosigenin (BDG) is a cucurbitane‐type triterpene isolated from Siratia grosvenori and has clear‐cut anti‐inflammatory effects, yet its benefit of pulmonary fibrosis (PF) remains unclear. In this study, we investigated the protective effects of BDG (10 mg/kg/day, for 14 days) against TGF‐β1‐stimulated mouse alveolar epithelial MLE‐12 cells and bleomycin (BLM)‐induced PF mice. In vitro experiments showed that BDG could inhibit epithelial‐mesenchymal transition (EMT) and oxidative stress. In vivo experiments indicated that BDG could ameliorate BLM‐induced PF in mice as evidenced by characteristic structural changes in histopathology, increased collagen deposition and reduced survival and weight of mice. The abnormal increased expressions of TGF‐β1, p‐Smad2/3, α‐SMA, COL‐I, and NOX4 and decreased expressions for Sirt1 and p‐AMPK were improved in BDG treatment. But these beneficial effects could be eliminated by co‐treatment with Compound C (CC, a selective AMPK inhibitor). Molecular docking technology also revealed the potential of BDG to activate AMPK. In summary, AMPK activation modulated by BDG not only ameliorated TGF‐β1/Smad2/3 signaling pathways but also partially mediated the suppression effects on EMT and oxidative stress, thus mediating the anti‐fibrotic effects.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.7535