{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:06Z","timestamp":1787028906920,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073764"],"award-info":[{"award-number":["82073764"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82073764"],"award-info":[{"award-number":["82073764"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Antioxidant peptides show significant activity and can be developed into functional foods for treating chronic diseases. Cigarette smoke components can cause damage or even apoptosis of lung cells, eventually leading to chronic lung diseases. Therefore, this study aimed to investigate the protective effects and mechanisms of Skipjack tuna peptides against in vitro cigarette smoke extract (CSE)-induced chronic obstructive pulmonary disease (COPD). The results demonstrated that tuna peptides DVGRG (S1), PHPR (S5), GRVPR (S6), and SVTEV (S7) significantly enhanced the activities of SOD, CAT, and GSH-Px by upregulating the mRNA transcription levels of Keap1 and Nrf2, consequently reducing ROS and MDA levels in CSE-induced COPD model of MLE-12 cells. Molecular docking analysis revealed that S1, S6, and S7 competitively inhibited the Keap1-Nrf2 interaction by binding to the Kelch domain of Keap1, whereas S5 operated through a non-competitive mechanism. These peptides also downregulated p65 mRNA expression and upregulated I\u03baB\u03b1 mRNA expression, leading to a significant reduction in inflammatory cytokines of IL-1\u03b2, IL-6, and TNF-\u03b1, thereby alleviating inflammatory responses. Furthermore, these peptides significantly inhibited CSE-induced apoptosis by restoring mitochondrial membrane potential and upregulating the Bcl-2\/Bax ratio. Additionally, S1, S5, S6, and S7 promoted MLE-12 cell migration in a concentration-dependent manner, suggesting a role in lung epithelial repair and regeneration. In conclusion, tuna peptides S1, S5, S6, and S7 exert antioxidant, anti-inflammatory, anti-apoptotic, and cell migration-promoting effects through the regulation of the Keap1\/Nrf2 and NF-\u03baB signaling pathways, as well as Bcl-2\/Bax apoptotic balance, providing a promising strategy for mitigating CSE-induced lung injury.<\/jats:p>","DOI":"10.3390\/md24040140","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:05:36Z","timestamp":1776348336000},"page":"140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antioxidant Peptides from Skipjack tuna: Ameliorate Function on Cigarette Smoke Extract-Induced COPD in Cell Model by Targeting Oxidative Stress, Inflammation and Apoptosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Yu-Hui","family":"Zeng","sequence":"first","affiliation":[{"name":"National and Provincial Joint Laboratory of Exploration, Utilization of Marine Aquatic Genetic Re-Sources, National Engineering Research Center of Marine Facilities Aquaculture, School of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-Yan","family":"Jin","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sheng","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Feng","family":"Chi","sequence":"additional","affiliation":[{"name":"National and Provincial Joint Laboratory of Exploration, Utilization of Marine Aquatic Genetic Re-Sources, National Engineering Research Center of Marine Facilities Aquaculture, School of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-9045","authenticated-orcid":false,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106751","DOI":"10.1016\/j.jff.2025.106751","article-title":"Exploring the structure\u2013activity relationships and molecular mechanisms of food-derived antioxidative peptides in mitigating oxidative stress: A comprehensive review","volume":"127","author":"Ali","year":"2025","journal-title":"J. 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