Zhang Ziqi, Zhang Yuan, Zhang Meiying, Yu Chenfeng, Yang Pingping, Xu Minxuan, Ling Jitao, Wu Yuting, Zhu Zicheng, Chen Yixuan, Shi Ao, Liu Xiao, Zhang Jing, Yu Peng, Zhang Deju
The Second Clinical Medical College, The Second Affiliated Hospital of Nanchang University, Nanchang University, Jiangxi, China.
Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Crit Rev Food Sci Nutr. 2025;65(8):1433-1464. doi: 10.1080/10408398.2023.2294164. Epub 2023 Dec 28.
NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), a member of the nucleotide-binding domain (NOD) and leucine-rich repeat sequence (LRR) protein (NLR) family, plays an essential role in the inflammation initiation and inflammatory mediator secretion, and thus is also associated with many disease progressions. Food-derived bioactive peptides (FDBP) exhibit excellent anti-inflammatory activity in both and models. They are encrypted in plant, meat, and milk proteins and can be released under enzymatic hydrolysis or fermentation conditions, thereby hindering the progression of hyperuricemia, inflammatory bowel disease, chronic liver disease, neurological disorders, lung injury and periodontitis by inactivating the NLRP3. However, there is a lack of systematic review around FDBP, NLRP3, and NLRP3-related diseases. Therefore, this review summarized FDBP that exert inhibiting effects on NLRP3 inflammasome from different protein sources and detailed their preparation and purification methods. Additionally, this paper also compiled the possible inhibitory mechanisms of FDBP on NLRP3 inflammasomes and its regulatory role in NLRP3 inflammasome-related diseases. Finally, the progress of cutting-edge technologies, including nanoparticle, computer-aided screening strategy and recombinant DNA technology, in the acquisition or encapsulation of NLRP3 inhibitory FDBP was discussed. This review provides a scientific basis for understanding the anti-inflammatory mechanism of FDBP through the regulation of the NLRP3 inflammasome and also provides guidance for the development of therapeutic adjuvants or functional foods enriched with these FDBP.
NLRP3（含核苷酸结合结构域（NOD）、富含亮氨酸重复序列（LRR）蛋白3）是核苷酸结合结构域（NOD）和富含亮氨酸重复序列（LRR）蛋白（NLR）家族的成员，在炎症起始和炎症介质分泌中起重要作用，因此也与许多疾病的进展相关。食物源生物活性肽（FDBP）在体内和体外模型中均表现出优异的抗炎活性。它们存在于植物、肉类和牛奶蛋白中，在酶解或发酵条件下可被释放出来，从而通过使NLRP3失活来阻碍高尿酸血症、炎症性肠病、慢性肝病、神经紊乱、肺损伤和牙周炎的进展。然而，目前缺乏关于FDBP、NLRP3以及与NLRP3相关疾病的系统综述。因此，本综述总结了来自不同蛋白质来源的对NLRP3炎性小体具有抑制作用的FDBP，并详细介绍了它们的制备和纯化方法。此外，本文还梳理了FDBP对NLRP3炎性小体可能的抑制机制及其在NLRP3炎性小体相关疾病中的调节作用。最后，讨论了包括纳米颗粒、计算机辅助筛选策略和重组DNA技术在内的前沿技术在获取或封装NLRP3抑制性FDBP方面的进展。本综述为通过调节NLRP3炎性小体来理解FDBP的抗炎机制提供了科学依据，也为开发富含这些FDBP的治疗佐剂或功能性食品提供了指导。
