A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway
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...
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MDPI AG
2025-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/5/583 |
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| author | Junyong Wang Wenxiu Zhang Rijun Zhang Xuelian Zhao Jing Zhang Yichen Zhou Yucui Tong Zaheer Abbas Zhenzhen Li Haosen Zhang Di Yang Sichao Chen Cong Hu Dayong Si Xubiao Wei |
| author_facet | Junyong Wang Wenxiu Zhang Rijun Zhang Xuelian Zhao Jing Zhang Yichen Zhou Yucui Tong Zaheer Abbas Zhenzhen Li Haosen Zhang Di Yang Sichao Chen Cong Hu Dayong Si Xubiao Wei |
| author_sort | Junyong Wang |
| collection | DOAJ |
| description | 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-Aβ (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 (H<sub>2</sub>O<sub>2</sub>-induced oxidative damage in HepG2 cells) and in vivo (CCl<sub>4</sub>-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. |
| format | Article |
| id | doaj-art-5912e6a87781478e8008ce04d0a5ff16 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-5912e6a87781478e8008ce04d0a5ff162025-08-20T03:47:48ZengMDPI AGAntioxidants2076-39212025-05-0114558310.3390/antiox14050583A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling PathwayJunyong Wang0Wenxiu Zhang1Rijun Zhang2Xuelian Zhao3Jing Zhang4Yichen Zhou5Yucui Tong6Zaheer Abbas7Zhenzhen Li8Haosen Zhang9Di Yang10Sichao Chen11Cong Hu12Dayong Si13Xubiao Wei14Laboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaBeijing Dabeinong Technology Group Co., Ltd., Beijing 100194, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaLaboratory of Feed Biotechnology, State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, ChinaOxidative 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-Aβ (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 (H<sub>2</sub>O<sub>2</sub>-induced oxidative damage in HepG2 cells) and in vivo (CCl<sub>4</sub>-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.https://www.mdpi.com/2076-3921/14/5/583hybrid peptideoxidative stressKEAP1-NRF2hydrogen peroxideliver damage |
| spellingShingle | Junyong Wang Wenxiu Zhang Rijun Zhang Xuelian Zhao Jing Zhang Yichen Zhou Yucui Tong Zaheer Abbas Zhenzhen Li Haosen Zhang Di Yang Sichao Chen Cong Hu Dayong Si Xubiao Wei A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway Antioxidants hybrid peptide oxidative stress KEAP1-NRF2 hydrogen peroxide liver damage |
| title | A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway |
| title_full | A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway |
| title_fullStr | A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway |
| title_full_unstemmed | A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway |
| title_short | A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway |
| title_sort | novel hybrid peptide vlp aβ exhibits antioxidant activity in vitro and in vivo via keap1 nrf2 are signaling pathway |
| topic | hybrid peptide oxidative stress KEAP1-NRF2 hydrogen peroxide liver damage |
| url | https://www.mdpi.com/2076-3921/14/5/583 |
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