{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:37:37Z","timestamp":1793133457987,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1300700"],"award-info":[{"award-number":["2022YFD1300700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFD1300400"],"award-info":[{"award-number":["2024YFD1300400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["32402776"],"award-info":[{"award-number":["32402776"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China","award":["2022YFD1300700"],"award-info":[{"award-number":["2022YFD1300700"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["2024YFD1300400"],"award-info":[{"award-number":["2024YFD1300400"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["32402776"],"award-info":[{"award-number":["32402776"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Xinjiang Uygur Autonomous Region \u201cTianchi Talent\u201d Introduction Program","award":["2022YFD1300700"],"award-info":[{"award-number":["2022YFD1300700"]}]},{"name":"Xinjiang Uygur Autonomous Region \u201cTianchi Talent\u201d Introduction Program","award":["2024YFD1300400"],"award-info":[{"award-number":["2024YFD1300400"]}]},{"name":"Xinjiang Uygur Autonomous Region \u201cTianchi Talent\u201d Introduction Program","award":["32402776"],"award-info":[{"award-number":["32402776"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress plays a crucial role in the development and progression of various diseases. Antioxidant peptides have attracted great attention in agricultural, food, and clinical fields due to their low toxicity, high efficacy, and easy absorption, but the development of antioxidant peptides and their in-depth molecular mechanisms are still lacking. The previous study established a platform for the high-throughput design and screening of multifunctional peptides and successfully identified a novel hybrid peptide, VLP-A\u03b2 (VA), which exhibits both antioxidant and immunomodulatory properties. This study aimed to evaluate the antioxidant activity of VA and investigate the underlying molecular mechanisms. The antioxidant effects of VA were evaluated using both in vitro (H2O2-induced oxidative damage in HepG2 cells) and in vivo (CCl4-induced liver damage in mice) models. VA exhibited significant antioxidant activity both in vitro and in vivo, significantly improving the cell viability and increasing the levels of antioxidant enzymes (SOD, CAT, GSH-Px) to alleviate oxidative stress. These findings indicated that the antioxidant effect of VA is dependent on NRF2, as evidenced by NRF2 knockdown experiments. Further investigation revealed that VA alleviates oxidative stress by modulating the KEAP1-NRF2-ARE signaling pathway. These findings provide insights into the properties of the antioxidant peptide VA, expand the understanding of its molecular mechanisms, and suggest new opportunities for developing VA as a novel functional agent in the agricultural, food, and clinical industries.<\/jats:p>","DOI":"10.3390\/antiox14050583","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T12:18:06Z","timestamp":1747052286000},"page":"583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Novel Hybrid Peptide VLP-A\u03b2 Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2158-2865","authenticated-orcid":false,"given":"Junyong","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucui","family":"Tong","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, 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Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sichao","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Hu","sequence":"additional","affiliation":[{"name":"Beijing Dabeinong Technology Group Co., Ltd., Beijing 100194, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayong","family":"Si","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41580-023-00645-4","article-title":"Understanding mechanisms of antioxidant action in health and 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