<br>(–)-丁香树脂醇通过改善肠上皮屏障功能和抑制炎症反应来减轻溃疡性结肠炎,Phytomedicine

当前位置： X-MOL 学术 › Phytomedicine › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

(–)-丁香树脂醇通过改善肠上皮屏障功能和抑制炎症反应来减轻溃疡性结肠炎
Phytomedicine ( IF 6.7 ) Pub Date : 2023-12-23 , DOI: 10.1016/j.phymed.2023.155292
Yunhe Liu ₁ , Junzhe Wu ₁ , Luying Tan ₁ , Zhuoqiao Li ₁ , Peng Gao ₁ , Shanmei He ₁ , Qianyun Wang ₁ , Daohao Tang ₁ , Cuizhu Wang ₂ , Fang Wang ₃ , Pingya Li ₂ , Jinping Liu ₂

Affiliation

背景

(–)-Syringaresinol (SYR) 是一种天然木脂素，具有显着的抗氧化和抗炎活性，具有多种药理功效，包括心脏保护、抗菌、抗癌和抗衰老作用。结果表明，(+)-丁香树脂醇二葡萄糖苷对溃疡性结肠炎 (UC) 的功效归因于活性代谢物 (+)-丁香树脂醇（SYR 的对映体）。然而，SYR对UC的疗效仍不清楚，相关的分子机制尚未揭示

目的

本研究旨在评估 SYR 对 UC 的保护作用及其潜在机制

研究设计和方法

我们在脂多糖(LPS) 诱导的 Caco-2 细胞模型和葡聚糖硫酸钠(DSS) 诱导的 UC 小鼠模型中检查了 SYR 对肠上皮屏障的保护作用及其抑制炎症反应的能力。我们还利用转录组分析和蛋白质印迹分析探索了 SYR 调节的潜在信号通路

结果

在 Caco-2 细胞中，SYR 显着增加跨上皮电阻，降低肿瘤坏死因子-α (TNF- α ) 、白细胞介素-6 (IL-6)、干扰素-γ (IFN- γ )和环氧合酶-2（ COX-2) 水平，并增强细胞紧密连接蛋白的表达和分布。在UC小鼠中，口服SYR（10、20、40 mg·kg ^-1 ）剂量依赖性地增加体重、结肠长度和紧密连接蛋白表达，降低疾病活动指数评分、脾系数、细胞因子血清水平、细菌移位和肠道损伤，还保留了结肠粘膜细胞的超微结构。转录组学表明 SYR 的抗 UC 作用是通过 PI3K-Akt/MAPK/Wnt 信号通路介导的。结论：综上所述，SYR通过增强肠上皮屏障功能和减轻炎症反应，有效减轻UC的发展。植物衍生产品 SYR 可能是治疗 UC 的潜在有效药物。

"点击查看英文标题和摘要"

(–)-Syringaresinol attenuates ulcerative colitis by improving intestinal epithelial barrier function and inhibiting inflammatory responses

Background

(–)-Syringaresinol (SYR), a natural lignan with significant antioxidant and anti-inflammatory activities, possesses various pharmacological benefits including cardio-protective, antibacterial, anticancer, and anti-aging effects. It was shown that the effectiveness of (+)-syringaresinol diglucoside on the ulcerative colitis (UC) was attributed to the active metabolite (+)-syringaresinol (the enantiomor of SYR). However, the efficacy of SYR against UC remains unclear, and the associated molecular mechanism has not been revealed yet

Purpose

This study aimed to assess the protective effect of SYR in UC and its underlying mechanism

Study design and methods

We examined SYR's protective impact on the intestinal epithelial barrier and its ability to inhibit inflammatory responses in both a lipopolysaccharide (LPS)-induced Caco-2 cell model and a dextran sodium sulfate (DSS)-induced UC mouse model. We also explored the potential signaling pathways regulated by SYR using transcriptome analysis and western blot assay

Results

In Caco-2 cells, SYR significantly increased trans-epithelial electrical resistance, reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-γ (IFN-γ), and cyclooxygenase-2 (COX-2) levels, and enhanced cellular tight junction protein expression and distribution. In mice with UC, oral treatment with SYR (10, 20, 40 mg·kg⁻¹) dose-dependently increased body weight, colon length, and expression of tight junction proteins, decreased disease activity index score, spleen coefficient, cytokine serum levels, bacterial translocation, and intestinal damage, and also preserved the ultrastructure of colonic mucosal cells. Transcriptomics indicated that the anti-UC effect of SYR is mediated via the PI3K-Akt/MAPK/Wnt signaling pathway. Conclusion: In summary, SYR effectively mitigated the development of UC by enhancing the intestinal epithelial barrier function and attenuating the inflammatory response. The plant-derived product SYR might be a potentially effective therapeutical agent against UC.

更新日期：2023-12-23

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南