A novel antioxidant peptide DD12 (DWPDARGIWHND) derived from dry cured ham alleviates H2O2-induced oxidative damage via the Keap1-Nrf2-ARE pathway

IF 8.8 1区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Food Research International Pub Date : 2026-04-30 Epub Date: 2026-01-30 DOI:10.1016/j.foodres.2026.118404

Ying-dao Nan , Si-qi Chen , Guan-hao Li , Ting-yu Li , Bai-de Mu , Juan Wang , Jian Feng , Hong-mei Li , Chun-xiang Piao

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Abstract

This study investigated the antioxidant mechanism of the dry-cured ham-derived peptide DD12 and its regulatory effect on the Keap1-Nrf2-ARE signaling pathway. Network pharmacological analysis showed that DD12 was associated with multiple antioxidant targets, and KEGG analysis revealed that it may regulate 112 signaling pathways, especially the Keap1-Nrf2 pathway. PPI network analysis identified five key targets, and molecular docking demonstrated that DD12 binds to NFE2L2 with high affinity. Luciferase reporter gene analysis confirmed that DD12 activated the ARE. Moreover, DD12 elevated SOD, CAT, and GSH-Px activities, and MDA and ROS levels were reduced by 54.46% and 67.39%, respectively in H₂O₂-induced Caco-2 cells. Western blot analysis demonstrated that DD12 promotes Nrf2 nuclear translocation and increased Nrf2, NQO1, HO-1, and decreased Keap1 mRNA and protein expression, indicating that DD12 inhibited H₂O₂-induced oxidative damage. Thus, DD12 acts as a potential antioxidant by activating the Keap1-Nrf2-ARE pathway.

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从干腌火腿中提取的一种新型抗氧化肽DD12 （DWPDARGIWHND）可通过Keap1-Nrf2-ARE途径减轻h2o2诱导的氧化损伤

本研究探讨了干腌火腿衍生肽DD12的抗氧化机制及其对Keap1-Nrf2-ARE信号通路的调控作用。网络药理学分析显示DD12与多个抗氧化靶点相关，KEGG分析显示其可能调控112条信号通路，尤其是Keap1-Nrf2通路。PPI网络分析确定了5个关键靶点，分子对接表明DD12与NFE2L2具有高亲和力。荧光素酶报告基因分析证实DD12激活了ARE。此外，DD12使h2o2诱导的Caco-2细胞SOD、CAT和GSH-Px活性升高，MDA和ROS水平分别降低54.46%和67.39%。Western blot分析显示，DD12促进Nrf2核易位，增加Nrf2、NQO1、HO-1的表达，降低Keap1 mRNA和蛋白的表达，表明DD12抑制h2o2诱导的氧化损伤。因此，DD12通过激活Keap1-Nrf2-ARE通路作为潜在的抗氧化剂。

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来源期刊

Food Research International 工程技术-食品科技

CiteScore

12.50

自引率

7.40%

发文量

1183

审稿时长

79 days

期刊介绍： Food Research International serves as a rapid dissemination platform for significant and impactful research in food science, technology, engineering, and nutrition. The journal focuses on publishing novel, high-quality, and high-impact review papers, original research papers, and letters to the editors across various disciplines in the science and technology of food. Additionally, it follows a policy of publishing special issues on topical and emergent subjects in food research or related areas. Selected, peer-reviewed papers from scientific meetings, workshops, and conferences on the science, technology, and engineering of foods are also featured in special issues.