Yang Po-Yu, Hsieh Pei-Ling, Yeh Jung-Chun, Ho Chun-Te, Liao Yi-Wen, Wei Yu-Lei, Wang Shih-Min, Yu Cheng-Chia, Chu Pei-Ming
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
J Dent Sci. 2025 Apr;20(2):911-918. doi: 10.1016/j.jds.2024.08.021. Epub 2024 Sep 8.
BACKGROUND/PURPOSE: Natural products are gaining increasing recognition as an alternative source for alleviating fibrosis as they can regulate various mediators or pathways against fibrosis by targeting non-coding RNAs. In the current study, we aimed to investigate the therapeutic effects of osthole in oral submucous fibrosis (OSF), a precancerous condition of the oral cavity.
The cytotoxicity of osthole to normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues was assessed using MTT assay. Collagen gel contraction and transwell migration assays were conducted to examine the myofibroblast activities. Besides, the expression of TGF-β/Smad2 signaling as well as α-SMA and type I collagen were measured. Additionally, RNA sequencing was used to identify a potential target involved in the anti-fibrotic effect of osthole.
Osthole exhibited a higher cytotoxic effect on fBMFs compared to normal BMFs and dose-dependently reduced several myofibroblast activities, including collagen gel contractility and transwell migration ability. In addition, the expression of the TGF-β/Smad2 pathway was inhibited along with a lower expression of α-SMA and type I collagen in osthole-receiving cells. Moreover, the administration of osthole downregulated the expression of NCK1-AS1 in fBMFs, which was proven to mediate the anti-fibrosis property of osthole.
Our results indicate that osthole may be a promising compound to inhibit the progression of OSF.
背景/目的：天然产物作为缓解纤维化的替代来源正日益受到认可，因为它们可以通过靶向非编码RNA来调节各种抗纤维化介质或途径。在本研究中，我们旨在研究蛇床子素对口腔黏膜下纤维化（OSF）（一种口腔癌前病变）的治疗效果。
采用MTT法评估蛇床子素对源自OSF组织的正常和纤维化颊黏膜成纤维细胞（fBMF）的细胞毒性。进行胶原凝胶收缩和Transwell迁移试验以检测肌成纤维细胞活性。此外，检测TGF-β/Smad2信号通路以及α-SMA和I型胶原的表达。另外，使用RNA测序来鉴定参与蛇床子素抗纤维化作用的潜在靶点。
与正常BMF相比，蛇床子素对fBMF表现出更高的细胞毒性，并剂量依赖性地降低了几种肌成纤维细胞活性，包括胶原凝胶收缩性和Transwell迁移能力。此外，在接受蛇床子素处理的细胞中，TGF-β/Smad2信号通路的表达受到抑制，同时α-SMA和I型胶原的表达也降低。此外，给予蛇床子素可下调fBMF中NCK1-AS1的表达，这被证明介导了蛇床子素的抗纤维化特性。
我们的结果表明，蛇床子素可能是一种有前途的抑制OSF进展的化合物。
