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中华鳖肽通过激活Nrf2/Keap1信号通路的抗衰老功能及其构效关系

Antiaging function of Chinese pond turtle () peptide through activation of the Nrf2/Keap1 signaling pathway and its structure-activity relationship.

作者信息

Wang Qianqian, Yang Zherui, Zhuang Jiachen, Zhang Junhui, Shen Fei, Yu Peng, Zhong Hao, Feng Fengqin

机构信息

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China.

Yuyao Lengjiang Turtle Industry, Ningbo, China.

出版信息

Front Nutr. 2022 Jul 22;9:961922. doi: 10.3389/fnut.2022.961922. eCollection 2022.

Abstract

Chinese pond turtle is a traditional nourishing food with high nutritional value and bioactivity and has been considered a dietary remedy for prolonging the lifespan since ancient times. However, only limited information about their effects on longevity is available. This study was performed to assess the antioxidant activities and antiaging potential of Chinese pond turtle peptide (CPTP) using model and uncover the possible mechanisms underlying the beneficial effects. CPTP exhibited excellent antioxidant capability with values of 3.31, 1.93, and 9.52 mg/ml for 1,1-diphenyl-2-pycryl-hydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazo-line-6-sulfonic acid) diammonium salt (ABTS), and hydroxyl radical scavenging, respectively. , 0.8% of CPTP significantly extended the mean and median lifespan of female flies by 7.66 and 7.85%, followed by enhanced resistance to oxidative and heat stress. Besides, CPTP remarkably increased the antioxidant enzyme activities and diminished the peroxide product accumulation. Furthermore, CPTP upregulated the relative mRNA expression of antioxidant-related genes, including nuclear factor-erythroid-2-like 2 () and its downstream target genes, while downregulated the expression of Kelch-like ECH-associated protein 1 (). Taken together, CPTP displayed promising potential in both antioxidant and antiaging effects on flies by targeting the Nrf2/Keap1 pathway. Further peptide sequence determination revealed that 89.23% of peptides from the identified sequences in CPTP could exert potential inhibitory effects on Keap1. Among these peptides, ten representative peptide sequences could actively interact with the binding sites of Keap1-Nrf2 interaction through hydrogen bonds, van der Walls, hydrophobic interactions, and electrostatic interactions. Conclusively, CPTP could be utilized as health-promoting bioactive peptide with antioxidant and antiaging capacities.

摘要

中华草龟是一种具有高营养价值和生物活性的传统滋补食品,自古以来就被视为延年益寿的食疗佳品。然而,关于它们对寿命影响的信息有限。本研究旨在使用模型评估中华草龟肽(CPTP)的抗氧化活性和抗衰老潜力,并揭示其有益作用的潜在机制。CPTP表现出优异的抗氧化能力,对1,1-二苯基-2-苦基肼(DPPH)、2,2'-联氮双(3-乙基苯并噻唑啉-6-磺酸)二铵盐(ABTS)和羟基自由基的清除值分别为3.31、1.93和9.52mg/ml。此外,0.8%的CPTP显著延长了雌性果蝇的平均寿命和中位数寿命,分别延长了7.66%和7.85%,同时增强了对氧化应激和热应激的抵抗力。此外,CPTP显著提高了抗氧化酶活性,减少了过氧化物产物的积累。此外,CPTP上调了抗氧化相关基因的相对mRNA表达,包括核因子红细胞2样2(Nrf2)及其下游靶基因,同时下调了kelch样ECH相关蛋白1(Keap1)的表达。综上所述,CPTP通过靶向Nrf2/Keap1途径在果蝇的抗氧化和抗衰老作用方面显示出有前景的潜力。进一步的肽序列测定表明,CPTP中鉴定序列的89.23%的肽对Keap1可能具有潜在的抑制作用。在这些肽中,十个代表性肽序列可以通过氢键、范德华力、疏水相互作用和静电相互作用与Keap1-Nrf2相互作用的结合位点积极相互作用。总之,CPTP可作为具有抗氧化和抗衰老能力的促进健康的生物活性肽。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a448/9355154/21683884954e/fnut-09-961922-g001.jpg

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