Jilin Provincial Key Laboratory of Nutrition and Functional Food/College of Food Science and Engineering, Jilin University, Changchun 130062, P. R. China.
J Agric Food Chem. 2024 Jun 5;72(22):12340-12355. doi: 10.1021/acs.jafc.4c00523. Epub 2024 May 22.
Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.
脂质过氧化（LP）导致细胞膜流动性和通透性改变，影响正常细胞功能，并可能引发细胞凋亡或坏死。这个过程与许多疾病的发生密切相关。有证据表明，食物源性植物多酚（FPP）中的酚羟基使它们成为有效的抗氧化剂，能够预防由细胞膜 LP 引发的疾病。适当摄入 FPP 可以通过激活 Nrf2/GPx4 途径来减轻细胞氧化应激，特别是对细胞膜磷脂的损伤。核因子 E2 相关因子 2（Nrf2）是一种氧化应激拮抗剂。受 Nrf2 调节的信号通路是生物体对活性氧和外源性化学物质等外部刺激的一种防御转导通路。谷胱甘肽过氧化物酶 4（GPx4）在 Nrf2 的调节下，是唯一具有特异性还原细胞膜脂过氧化物的酶，因此在调节细胞铁死亡和对抗氧化应激方面起着关键作用。本研究探讨了 FPP 的 Nrf2/GPx4 通路机制、抗氧化活性和 LP 机制。还强调了 FPP 对 LP 及其相关机制的生物保护特性，包括（i）激活 Nrf2/GPx4 途径，其中 GPx4 可能作为中心靶蛋白，（ii）调节抗氧化酶活性，导致 ROS 和其他过氧化物的产生减少，以及（iii）对 LP 和下游磷脂结构的抗氧化作用。总之，FPP 作为天然抗氧化剂在预防 LP 中起着至关重要的作用。然而，需要进一步深入分析 FPP 对多个信号通路的核心调控作用，并且需要在实验模型中进一步评估这些机制的联合作用。人体试验可以为研究和应用提供有价值的新方向。
