In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids
IntroductionOxidative stress plays an essential role in the pathogenesis of chronic diseases. Disrupting the Keap1-Nrf2 pathway by binding Keap1 is identified as a potential strategy to prevent oxidative stress-related chronic diseases. Therefore, of special interest is the utilization of dietary an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2023.1257172/full |
| _version_ | 1827862533197791232 |
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| author | Tianzhu Guan Canfeng Bian Zheng Ma |
| author_facet | Tianzhu Guan Canfeng Bian Zheng Ma |
| author_sort | Tianzhu Guan |
| collection | DOAJ |
| description | IntroductionOxidative stress plays an essential role in the pathogenesis of chronic diseases. Disrupting the Keap1-Nrf2 pathway by binding Keap1 is identified as a potential strategy to prevent oxidative stress-related chronic diseases. Therefore, of special interest is the utilization of dietary antioxidations from citrus, including narirutin, naringenin, hesperetin, hesperidin, naringin, neohesperidin dihydrochalcone, neohesperidin, and nobiletin, has been exploited as a prospective way to treat or prevent several human pathologies as Keap1-Nrf2 inhibitors for modulation of antioxidant properties.MethodsTo probe into the structural foundation of the molecular identification of citrus-derived antioxidations, we calculated the antioxidant responsive element activation ability of citrus-derived flavonoids after binding with Keap1. Also, the quantum chemistry properties and binding mode were performed theoretically with frontier molecular orbitals, molecular electrostatic potential analysis, molecular docking, and absorption, distribution, metabolism, excretion (ADME) calculation.Results and discussionExperimental findings combining computational assays revealed that the tested citrus-derived flavonoids can be grouped into strong agonists and weak agonists. The citrus-derived antioxidations were well housed in the bound zone of Keap1 via stable hydrogen bonding and hydrophobic interaction. Eventually, three of eight antioxidations were identified after ADME and physicochemical evaluations. The citrus-derived flavonoids were identified as potential dietary antioxidants of the Keap1-Nrf2 interaction, and can be used to improve oxidative stress-related chronic diseases. |
| first_indexed | 2024-03-12T13:56:37Z |
| format | Article |
| id | doaj.art-2c5d4b2c173847d6828fed0d99ecc1e8 |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-03-12T13:56:37Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-2c5d4b2c173847d6828fed0d99ecc1e82023-08-22T13:55:04ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2023-08-011010.3389/fnut.2023.12571721257172In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoidsTianzhu Guan0Canfeng Bian1Zheng Ma2School of Food Science and Engineering, Yangzhou University, Yangzhou, ChinaSchool of Food Science and Engineering, Yangzhou University, Yangzhou, ChinaDepartment of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, ChinaIntroductionOxidative stress plays an essential role in the pathogenesis of chronic diseases. Disrupting the Keap1-Nrf2 pathway by binding Keap1 is identified as a potential strategy to prevent oxidative stress-related chronic diseases. Therefore, of special interest is the utilization of dietary antioxidations from citrus, including narirutin, naringenin, hesperetin, hesperidin, naringin, neohesperidin dihydrochalcone, neohesperidin, and nobiletin, has been exploited as a prospective way to treat or prevent several human pathologies as Keap1-Nrf2 inhibitors for modulation of antioxidant properties.MethodsTo probe into the structural foundation of the molecular identification of citrus-derived antioxidations, we calculated the antioxidant responsive element activation ability of citrus-derived flavonoids after binding with Keap1. Also, the quantum chemistry properties and binding mode were performed theoretically with frontier molecular orbitals, molecular electrostatic potential analysis, molecular docking, and absorption, distribution, metabolism, excretion (ADME) calculation.Results and discussionExperimental findings combining computational assays revealed that the tested citrus-derived flavonoids can be grouped into strong agonists and weak agonists. The citrus-derived antioxidations were well housed in the bound zone of Keap1 via stable hydrogen bonding and hydrophobic interaction. Eventually, three of eight antioxidations were identified after ADME and physicochemical evaluations. The citrus-derived flavonoids were identified as potential dietary antioxidants of the Keap1-Nrf2 interaction, and can be used to improve oxidative stress-related chronic diseases.https://www.frontiersin.org/articles/10.3389/fnut.2023.1257172/fulldietary antioxidationscitrus-derived flavonoidsoxidative stressantioxidantKelch-like ECH-associated protein 1structure-activation relationship |
| spellingShingle | Tianzhu Guan Canfeng Bian Zheng Ma In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids Frontiers in Nutrition dietary antioxidations citrus-derived flavonoids oxidative stress antioxidant Kelch-like ECH-associated protein 1 structure-activation relationship |
| title | In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids |
| title_full | In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids |
| title_fullStr | In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids |
| title_full_unstemmed | In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids |
| title_short | In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids |
| title_sort | in vitro and in silico perspectives on the activation of antioxidant responsive element by citrus derived flavonoids |
| topic | dietary antioxidations citrus-derived flavonoids oxidative stress antioxidant Kelch-like ECH-associated protein 1 structure-activation relationship |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2023.1257172/full |
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