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探讨多糖通过调节 Nrf2 介导的抗氧化反应的分子机制、结构-活性关系及其应用前景。

Insights into the molecular mechanisms, structure-activity relationships and application prospects of polysaccharides by regulating Nrf2-mediated antioxidant response.

机构信息

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

出版信息

Carbohydr Polym. 2024 Jun 1;333:122003. doi: 10.1016/j.carbpol.2024.122003. Epub 2024 Feb 27.

DOI:10.1016/j.carbpol.2024.122003
PMID:38494201
Abstract

The occurrence and development of many diseases are closely related to oxidative stress. In this context, accumulating evidence suggests that Nrf2, as the master switch of cellular antioxidant signaling, plays a central role in controlling the expression of antioxidant genes. The core molecular mechanism of polysaccharides treatment of oxidative stress-induced diseases is to activate Keap1/Nrf2/ARE signaling pathway, promote nuclear translocation of Nrf2, and up-regulate the expression of antioxidant enzymes. However, recent studies have shown that other signaling pathways in which polysaccharides exert antioxidant effects, such as PI3K/Akt/GSK3β, JNK/Nrf2 and NF-κB, have complex crosstalk with Keap1/Nrf2/ARE, may have direct effects on the nuclear translocation of Nrf2. This suggests a new strategy for designing polysaccharides as modulators of Nrf2-dependent pathways to target the antioxidant response. Therefore, in this work, we investigate the crosstalk between Keap1/Nrf2/ARE and other antioxidant signaling pathways of polysaccharides by regulating Nrf2-mediated antioxidant response. For the first time, the structural-activity relationship of polysaccharides, including molecular weight, monosaccharide composition, and glycosidic linkage, is systematically elucidated using principal component analysis and cluster analysis. This review also summarizes the application of antioxidant polysaccharides in food, animal production, cosmetics and biomaterials. The paper has significant reference value for screening antioxidant polysaccharides targeting Nrf2.

摘要

许多疾病的发生和发展都与氧化应激密切相关。在这种情况下,越来越多的证据表明,Nrf2 作为细胞抗氧化信号的主开关,在控制抗氧化基因的表达中起着核心作用。多糖治疗氧化应激诱导疾病的核心分子机制是激活 Keap1/Nrf2/ARE 信号通路,促进 Nrf2 核易位,上调抗氧化酶的表达。然而,最近的研究表明,多糖发挥抗氧化作用的其他信号通路,如 PI3K/Akt/GSK3β、JNK/Nrf2 和 NF-κB,与 Keap1/Nrf2/ARE 之间存在复杂的串扰,可能直接影响 Nrf2 的核易位。这为设计作为 Nrf2 依赖性途径调节剂的多糖以针对抗氧化反应提供了一种新策略。因此,在这项工作中,我们通过调节 Nrf2 介导的抗氧化反应来研究 Keap1/Nrf2/ARE 与多糖的其他抗氧化信号通路之间的串扰。本文首次使用主成分分析和聚类分析系统地阐明了多糖的结构-活性关系,包括分子量、单糖组成和糖苷键。本文还总结了抗氧化多糖在食品、动物生产、化妆品和生物材料中的应用。本文对筛选针对 Nrf2 的抗氧化多糖具有重要的参考价值。

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