Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process
| Autor: | Zhang Xuan, Cheng Mengqun, Jian-bing Yin, Wang Yongyan, Zhi-peng Hong, Wang Yingxia, Chen Cheng |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Pulmonary Fibrosis Iridoid Glucosides Anti-Inflammatory Agents Biophysics Pharmacology Bleomycin Biochemistry Proinflammatory cytokine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fibrosis Pulmonary fibrosis medicine Animals Immunologic Factors Lung Molecular Biology Dose-Response Relationship Drug medicine.diagnostic_test business.industry Interstitial lung disease Pneumonia Cell Biology Pirfenidone medicine.disease CTGF Treatment Outcome 030104 developmental biology Bronchoalveolar lavage chemistry 030220 oncology & carcinogenesis Cytokines business medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 495:2396-2403 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2017.12.112 |
| Popis: | Pulmonary fibrosis (PF) is a chronic and ultimately fatal interstitial lung disease of various causes. The advent of nintedanib and pirfenidone provides treatment options for PF patients for the first time. However, the adverse effects of the two drugs such as gastrointestinal disorders and hepatic dysfunction often lead to treatment discontinuation. Gentiopicroside (GPS) is a natural secoiridoid glycoside from gentian species of medicinal plants, and has a variety of pharmacological activities, including hepatoprotective and cholagogic, anti-inflammatory, antinociceptive, and smooth muscle relaxing activities. The present study aimed to investigate the therapeutical effects of GPS on bleomycin (BLM)-induced PF in mice. Severe lung inflammation and fibrosis were observed in BLM-treated mice. GPS significantly ameliorated inflammatory and fibrotic responses in lungs of PF mice which were confirmed by histopathological examinations including light microscopy and transmission electron microscopy. Additionally, GPS significantly decreased the levels of inflammatory cytokines including TNF-α and IL-1β in bronchoalveolar lavage fluid and reduced the content of hydroxyproline in lungs of PF mice. Furthermore, GPS significantly downregulated the expression of TGF-β1 and CTGF in lungs of PF mice. In vitro, GPS inhibited epithelial-mesenchymal transition of A549 cells stimulated by TGF-β1, in a dose-dependent manner. Our findings suggest that GPS has the potential as an ideal drug candidate for PF, as it has both anti-inflammatory and anti-fibrotic effects. Alveolar epithelial cells and TGF-β1 may be the main target cells and molecule of GPS on BLM-induced PF, respectively. |
| Databáze: | OpenAIRE |
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