关于槲皮素在非传染性疾病治疗潜力的新视角：以Nrf2为靶点对抗氧化应激与炎症
New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation
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影响因子:8.9
分区:医学1区 Top / 药学1区
发表日期:2024 Jun
作者:
Li Zhang, Li-Yue Xu, Fei Tang, Dong Liu, Xiao-Lan Zhao, Jing-Nan Zhang, Jia Xia, Jiao-Jiao Wu, Yu Yang, Cheng Peng, Hui Ao
DOI:
10.1016/j.jpha.2023.12.020
摘要
非传染性疾病（NCDs），包括心血管疾病、癌症、代谢疾病和骨骼疾病，已成为全球公共卫生的重大挑战。这些疾病的复杂发病机制与氧化应激和炎症损伤密切相关。核因子红细胞2相关因子2（Nrf2）是一种关键的转录因子，在调控抗氧化和抗炎反应中发挥重要作用，保护细胞免受氧化损伤和炎症介导的损伤。因此，针对Nrf2的治疗具有预防和治疗NCDs的潜力。槲皮素（Que）是一种广泛存在的类黄酮，具有显著的抗氧化和抗炎作用。它通过调节Nrf2信号通路，改善氧化应激和炎症。Que调节线粒体功能、细胞凋亡、自噬和细胞损伤标志物，从而调控氧化应激和炎症，突显其作为抗NCDs的治疗药物的潜力。本文首次探讨了NCD发病机制与Nrf2信号通路的密切关系，涉及神经退行性疾病（NDDs）、心血管疾病、癌症、器官损伤和骨损伤，并综述了Que在NCDs治疗中的可用性、药代动力学、药剂学及其临床应用。此外，还关注了其临床应用的挑战与前景。由于具有靶向Nrf2的特性，Que被认为是治疗NCDs的有潜力候选药物。
Abstract
Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.