State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China; Respiratory Department, Tianjin Medical University General Hospital, Tianjin, 300071, China.
Eur J Pharmacol. 2019 Dec 1;864:172712. doi: 10.1016/j.ejphar.2019.172712. Epub 2019 Oct 2.
Idiopathic pulmonary fibrosis (IPF) is a fatal growing problem, with limited therapeutic options. Transforming growth factor beta 1 (TGF-β1) plays a critical role in many pathological processes that characterize pulmonary fibrosis. Effective and well-tolerated antifibrotic agents that interfere with TGF-β1 signaling would be an ideal treatment but no such treatments are available. In this study, we identified that the natural compound, neohesperidin, antagonizes TGF-β1/Smad3 signaling. We found that neohesperidin not only inhibited the TGF-β1-induced injury to alveolar epithelial cells but also decreased the TGF-β1-induced myofibroblast differentiation, extracellular matrix production, and fibroblast migration. Furthermore, we obtained in vivo evidence that neohesperidin treatment inhibited bleomycin-induced lung injuries and even attenuated established pulmonary fibrosis in mice. Our data suggest that neohesperidin can target the critical signaling pathway and profibrogenic responses in progressive pulmonary fibrosis and may have a potential use in treatment.
特发性肺纤维化（IPF）是一个致命的日益严重的问题，治疗选择有限。转化生长因子β 1（TGF-β1）在许多特征为肺纤维化的病理过程中起着关键作用。有效的、耐受性良好的抗纤维化药物，能干扰 TGF-β1 信号通路，这将是一种理想的治疗方法，但目前尚无此类治疗方法。在这项研究中，我们发现天然化合物新橙皮苷能拮抗 TGF-β1/Smad3 信号。我们发现新橙皮苷不仅抑制了 TGF-β1 诱导的肺泡上皮细胞损伤，还减少了 TGF-β1 诱导的肌成纤维细胞分化、细胞外基质产生和成纤维细胞迁移。此外，我们获得了体内证据，表明新橙皮苷治疗可抑制博来霉素诱导的肺损伤，甚至减轻小鼠已建立的肺纤维化。我们的数据表明，新橙皮苷可以针对进行性肺纤维化中的关键信号通路和促纤维化反应，可能具有治疗用途。
