Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
Phytother Res. 2013 Mar;27(3):463-7. doi: 10.1002/ptr.4735. Epub 2012 Jun 2.
Naringenin, a natural predominant flavanone derived from plant food, has antifibrotic activity. The purposes of this study were to determine the effect of naringenin on myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs) and to determine the molecular mechanism of the effect of naringenin on NPDFs. NPDFs were incubated and treated with transforming growth factor (TGF)-β1. The expression of alpha smooth muscle actin (α-SMA), fibronectin, and collagen type I mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of those proteins was determined by immunofluorescence staining or Western blotting. Expression of several signaling molecules of the TGF-β1 pathway was evaluated by Western blot analysis. Naringenin inhibits expression of an indicator of myofibroblast differentiation (α-SMA) and ECM production, including collagen type 1 and fibronectin. Naringenin only suppressed the expression of extracellular signal-regulated protein kinase (pERK)1/2 among evaluated signaling molecules. PD98059 (a specific inhibitor of ERK1/2 kinase) also suppressed the increased expression of fibronectin, collagen type I, and α-SMA in TGF-β1-induced NPDFs. These results suggest the possibility that naringenin may play an inhibitory role in the production of the ECM in the development of nasal polyps.
柚皮苷是一种天然存在的主要类黄酮,来源于植物性食物,具有抗纤维化作用。本研究旨在确定柚皮苷对鼻息肉衍生成纤维细胞(NPDFs)中肌成纤维细胞分化和细胞外基质(ECM)产生的影响,并确定柚皮苷对 NPDFs 作用的分子机制。用转化生长因子(TGF)-β1 孵育和处理 NPDFs。通过逆转录-聚合酶链反应测定α平滑肌肌动蛋白(α-SMA)、纤维连接蛋白和 I 型胶原 mRNA 的表达,通过免疫荧光染色或 Western blot 测定这些蛋白质的表达。通过 Western blot 分析评估 TGF-β1 通路的几个信号分子的表达。柚皮苷抑制肌成纤维细胞分化(α-SMA)和 ECM 产生的标志物的表达,包括 I 型胶原和纤维连接蛋白。柚皮苷仅抑制评估的信号分子中细胞外信号调节蛋白激酶(pERK)1/2 的表达。PD98059(ERK1/2 激酶的特异性抑制剂)也抑制 TGF-β1 诱导的 NPDFs 中纤维连接蛋白、I 型胶原和 α-SMA 的表达增加。这些结果表明,柚皮苷可能在鼻息肉发展过程中 ECM 的产生中发挥抑制作用。