Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process
Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process
复制标题
龙胆苦苷通过抑制炎症和纤维化过程改善博莱霉素诱导的小鼠肺纤维化
DOI：
10.1016/j.bbrc.2017.12.112
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发表时间：
2018-01-22
影响因子：
3.1
通讯作者：
Hong, Zhi-peng
中科院分区：
文献类型：
--
作者：
Chen, Cheng;Wang, Yong-yan;Hong, Zhi-peng
肺纤维化(PF)是一种慢性的、最终致死的各种原因的间质性肺疾病。9tedanib和吡非尼酮的问世首次为PF患者提供了治疗选择。然而，这两种药物的不良反应，如胃肠功能紊乱和肝功能障碍，往往导致停止治疗。龙胆苦苷是从龙胆属药用植物中提取的一种天然环烯醚萜苷，具有多种药理活性，包括保肝利胆、抗炎、抗伤害性和舒血管活性。本研究旨在探讨GPS对博莱霉素(BLM)诱导的小鼠肺纤维化的治疗作用。BLM组小鼠出现严重的肺部炎症和纤维化。GPS能显着减轻肺纤维化小鼠的炎症和纤维化反应，包括光镜和透射电子显微镜在内的组织病理学检查证实这一点。此外，三七总皂甙还能显著降低肺泡灌洗液中炎性细胞因子TNF-α和IL-1β的水平，降低肺组织羟脯氨酸的含量。此外，GPS还能显著下调肺纤维化小鼠肺组织中转化生长因子β1和结缔组织生长因子的表达。在体外，GPS以剂量依赖的方式抑制转化生长因子-β1刺激的A549细胞上皮-间充质转化。我们的发现表明，GPS具有抗炎和抗纤维化的作用，因此有可能成为治疗PF的理想候选药物。肺泡上皮细胞和转化生长因子-β1可能分别是博莱姆诱导肺纤维化的主要靶细胞和分子。(C)2017 Elsevier Inc.保留所有权利。
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 -alpha and IL-1 beta in bronchoalveolar lavage fluid and reduced the content of hydroxyproline in lungs of PF mice. Furthermore, GPS significantly downregulated the expression of TGF-beta 1 and CTGF in lungs of PF mice. In vitro, GPS inhibited epithelial-mesenchymal transition of A549 cells stimulated by TGF-beta 1, 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-beta 1 may be the main target cells and molecule of GPS on BLM-induced PF, respectively. (C) 2017 Elsevier Inc. All rights reserved.