School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
The First School of Clinical Medical, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Biomed Pharmacother. 2024 Jun;175:116671. doi: 10.1016/j.biopha.2024.116671. Epub 2024 Apr 27.
DIREN is a SHE ethnic medicine with stasis-resolving, hemostasis, clearing heat, and removing toxin effects. It is clinically used in the treatment of gastrointestinal bleeding, such as ulcerative colitis (UC).
Fibrosis is one of the pathological changes in the progression of UC, which can make it challenging to respond to a treatment. We aimed to illuminate the role of DIREN in DSS-induced UC and tried to unveil its related mechanisms from two perspectives: intestinal inflammation and collagen deposition.
A 2.5 % dextran sulfate sodium (DSS) water solution was used to induce colitis in mice. The therapeutic effect of DIREN was assessed using the disease activity index, histopathological score, and colon length. Masson and Sirius Red staining was used to observe the fibrosis in the colon. Apoptosis of colonic epithelial cells was observed by TUNEL immunofluorescence staining. RNA-seq observed differential genes and enrichment pathways. Immunohistochemistry and RT-qPCR were used to detect the expression of molecules related to fibrosis and focal adhesion signaling in colon tissue.
The administration of DIREN resulted in a reduction of disease activity index (DAI) in mice with UC while simultaneously promoting an increase in colon length. DIREN mitigated the loss of goblet cells in the colon of UC mice and maintained the integrity of the intestinal mucosa barrier. Masson staining revealed a reduction in colonic fibrosis with DIREN treatment, while Sirius red staining demonstrated a decrease in collagen Ⅰ deposition. DIREN reduced apoptosis of colonic epithelial cells and the expression of genes, such as CDH2, ITGA1, and TGF-β2. Additionally, the results of GSEA analysis of colon tissue transcriptome showed that the differentially expressed genes were enriched in the focal adhesion pathway. DIREN was found to downregulate the protein expression of BAX, N-cadherin, β-catenin, Integrin A1, and Vinculin while upregulating the protein expression of BCL2. Additionally, it led to the co-expression of N-cadherin and α-SMA.
DIREN exerts a protective effect against DSS-induced UC by ameliorating colonic fibrosis via regulation of focal adhesion and the WNT/β-catenin signaling pathway, thereby inhibiting fibroblast migration and reducing collagen secretion.
地稔是畲族药，具有化瘀止血、清热解毒、消痈等功效。临床上用于治疗溃疡性结肠炎（UC）等胃肠道出血。
纤维化是 UC 进展过程中的一种病理变化，会使治疗反应变得困难。我们旨在阐明地稔在 DSS 诱导的 UC 中的作用，并试图从肠道炎症和胶原沉积两个方面揭示其相关机制。
采用 2.5%葡聚糖硫酸钠（DSS）水溶液诱导小鼠结肠炎。采用疾病活动指数、组织病理学评分和结肠长度评估地稔的治疗效果。Masson 和 Sirius Red 染色观察结肠纤维化。TUNEL 免疫荧光染色观察结肠上皮细胞凋亡。RNA-seq 观察差异基因和富集通路。免疫组织化学和 RT-qPCR 检测结肠组织中与纤维化和黏附斑信号相关分子的表达。
地稔给药可降低 UC 小鼠的疾病活动指数（DAI），同时促进结肠长度增加。地稔减轻了 UC 小鼠结肠中杯状细胞的丢失，并维持了肠黏膜屏障的完整性。Masson 染色显示地稔治疗后结肠纤维化减少，而 Sirius Red 染色显示胶原Ⅰ沉积减少。地稔减少了结肠上皮细胞的凋亡和 CDH2、ITGA1 和 TGF-β2 等基因的表达。此外，结肠组织转录组 GSEA 分析结果表明，差异表达基因富集在黏附斑通路。地稔下调 BAX、N-钙黏蛋白、β-连环蛋白、整合素 A1 和 vinculin 的蛋白表达，上调 BCL2 的蛋白表达。此外，它还导致 N-钙黏蛋白和 α-SMA 的共表达。
地稔通过调节黏附斑和 WNT/β-连环蛋白信号通路改善结肠纤维化，从而抑制成纤维细胞迁移和减少胶原分泌，对 DSS 诱导的 UC 发挥保护作用。
