Graduate Institute of Natural Healing Sciences, Nanhua University, Chia-Yi 622, Taiwan.
J Agric Food Chem. 2010 Nov 24;58(22):11653-61. doi: 10.1021/jf1031668. Epub 2010 Oct 19.
Lonicera japonica (Caprifoliaceae) has been known as an anti-inflammatory herb in traditional Chinese medicine for thousands of years and is used constantly for upper respiratory tract infections. Luteolin, an active flavonoid compound isolated from Lonicera japonica, has a spectrum of biological activities, especially with antioxidative and anti-inflammatory properties. However, whether luteolin has a direct inhibitory effect on lung fibrosis has not been established. In this study, we examined the effects of luteolin on lung fibrosis both in vivo and in vitro. We found that oral administration of luteolin (10 mg/kg) efficiently suppressed the neutrophil infiltration as well as TNF-α and IL-6 elevation in the bronchoalveolar lavage fluid in bleomycin-instilled C57BL/6J mice. Luteolin also alleviated collagen deposition, TGF-β1 expression, and lung fibrosis upon bleomycin instillation. A similar tendency was observed in both early and delayed luteolin-treated groups. Next, our in vitro studies showed that luteolin inhibited TGF-β1-induced α-SMA, type I collagen, and vimentin expression in primary cultured mouse lung fibroblasts. Moreover, luteolin significantly blocked TGF-β1-mediated epithelial marker (E-cadherin) downregulation and mesenchymal cell markers (fibronectin and vimentin) upregulation, as well as retaining epithelial morphology in human alveolar epithelial-derived A549 cells. Additionally, luteolin could attenuate TGF-β1-induced Smad3 phosphorylation in both lung fibroblasts and A549 cells. These findings suggest that luteolin has a potent antifibrotic activity; this effect was mediated, at least in part, by inhibition of lung inflammation and suppression of myofibroblast differentiation as well as epithelial-to-mesenchymal transition.
忍冬（忍冬科）作为一种传统中药的抗炎草药，在中国已经使用了数千年，被广泛用于治疗上呼吸道感染。木犀草素，一种从忍冬中分离出来的活性黄酮类化合物，具有广泛的生物活性，特别是具有抗氧化和抗炎特性。然而，木犀草素是否对肺纤维化有直接的抑制作用尚未确定。在这项研究中，我们研究了木犀草素在体内和体外对肺纤维化的作用。我们发现，木犀草素（10mg/kg）口服给药可有效抑制博莱霉素诱导的 C57BL/6J 小鼠支气管肺泡灌洗液中的中性粒细胞浸润以及 TNF-α 和 IL-6 的升高。木犀草素还可减轻博莱霉素诱导的胶原沉积、TGF-β1 表达和肺纤维化。在早期和延迟给予木犀草素治疗的两组中均观察到类似的趋势。接下来，我们的体外研究表明，木犀草素抑制了 TGF-β1 诱导的原代培养小鼠肺成纤维细胞中 α-SMA、I 型胶原和波形蛋白的表达。此外，木犀草素可显著阻断 TGF-β1 介导的上皮标志物（E-钙粘蛋白）下调和间充质细胞标志物（纤维连接蛋白和波形蛋白）上调，并维持人肺泡上皮源性 A549 细胞的上皮形态。此外，木犀草素可减弱 TGF-β1 在肺成纤维细胞和 A549 细胞中诱导的 Smad3 磷酸化。这些发现表明，木犀草素具有很强的抗纤维化活性；这种作用至少部分是通过抑制肺炎症和抑制肌成纤维细胞分化以及上皮-间充质转化来介导的。
