Epimedium polysaccharides ameliorate ulcerative colitis by inhibiting oxidative stress and regulating autophagy.

IF 3.3 2区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY Journal of the Science of Food and Agriculture Pub Date : 2024-11-14 DOI:10.1002/jsfa.14037

Linxian Zhao, Tao Jiang, Yuxin Zhang, Zhen Shen

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Abstract

Background: Epimedium polysaccharide (EPS) is a bioactive compound derived from the traditional Chinese herb Epimedium brevicornum. The objective of this study was to investigate the protective effects of EPS on ulcerative colitis (UC) and to elucidate the underlying mechanisms involved.

Results: The findings showed that EPS treatment mitigated UC symptoms, including weight loss, anal bleeding, elevated disease activity index (DAI), and colon shortening. Hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining demonstrated that EPS alleviated histopathological damage and improved the integrity of the colonic mucosa. Mechanistically, EPS was found to substantially decrease inflammation by inhibiting the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and to alleviate oxidative stress through modulation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (Keap1/Nrf2) pathway. Notably, EPS failed to exert protective effects against dextran sulfate sodium (DSS)-induced UC in Nrf2-knockout (Nrf2^-/-) mice. Additionally, Western blotting and immunohistochemical analysis demonstrated that EPS facilitated autophagy via the adenosine monophosphate-dependent protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway. In vitro experiments revealed that EPS effectively suppressed lipopolysaccharide (LPS)-mediated cellular damage and oxidative stress by regulating Keap1/Nrf2 pathway. Transcriptomic analysis of LPS-treated Caco-2 cells following EPS treatment revealed a significant up-regulation of Nrf2 expression.

Conclusion: In conclusion, the findings of this study suggest that EPS exerts protective effects against DSS-induced UC through the inhibition of the TLR4/NF-κB signaling pathway, regulation of the Keap1/Nrf2 pathway, and promotion of autophagy via the AMPK/mTOR pathway. Consequently, EPS may represent a potential therapeutic target for the treatment of UC. © 2024 Society of Chemical Industry.

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淫羊藿多糖可通过抑制氧化应激和调节自噬来改善溃疡性结肠炎。

背景：淫羊藿多糖（EPS）是从传统中草药淫羊藿中提取的一种生物活性化合物。本研究的目的是探讨 EPS 对溃疡性结肠炎（UC）的保护作用，并阐明其中的潜在机制：结果：研究结果表明，EPS治疗可减轻溃疡性结肠炎的症状，包括体重减轻、肛门出血、疾病活动指数（DAI）升高和结肠缩短。血红素和伊红（H&E）以及阿尔新蓝-周期酸-希夫（AB-PAS）染色显示，EPS减轻了组织病理学损伤，改善了结肠粘膜的完整性。从机理上讲，EPS 可通过抑制 Toll 样受体 4/核因子-κB（TLR4/NF-κB）信号通路来大幅减少炎症，并通过调节 Kelch 样 ECH 相关蛋白 1/核因子红细胞衍生 2-like 2（Keap1/Nrf2）通路来减轻氧化应激。值得注意的是，EPS 对右旋糖酐硫酸钠（DSS）诱导的 Nrf2 基因敲除（Nrf2-/-）小鼠 UC 没有保护作用。此外，Western 印迹和免疫组化分析表明，EPS 可通过单磷酸腺苷依赖性蛋白激酶/哺乳动物雷帕霉素靶标（AMPK/mTOR）途径促进自噬。体外实验显示，EPS通过调节Keap1/Nrf2通路，有效抑制了脂多糖（LPS）介导的细胞损伤和氧化应激。EPS 处理后，对经 LPS 处理的 Caco-2 细胞进行转录组分析，发现 Nrf2 的表达显著上调：总之，本研究结果表明，EPS通过抑制TLR4/NF-κB信号通路、调节Keap1/Nrf2通路以及通过AMPK/mTOR通路促进自噬，对DSS诱导的UC具有保护作用。因此，EPS 可能是治疗 UC 的潜在治疗靶点。© 2024 化学工业协会。

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来源期刊

Journal of the Science of Food and Agriculture 工程技术-农业综合

CiteScore

8.10

自引率

4.90%

发文量

634

审稿时长

3.1 months

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