Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures. In this study, the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor (erythroid-2-derived)-related factor 2 (Nrf2) pathway predicted by network pharmacology. And the antioxidant effect and mechani...

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Main Authors: Meijing Zhang, Gaoshuai Zhang, Xiangxing Meng, Xinxin Wang, Jiao Xie, Shaoshu Wang, Biao Wang, Jilite Wang, Suwen Liu, Qun Huang, Xu Yang, Jing Li, Hao Wang
Format: Article
Language:English
Published: Tsinghua University Press 2024-07-01
Series:Food Science and Human Wellness
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Online Access:https://www.sciopen.com/article/10.26599/FSHW.2022.9250155
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author Meijing Zhang
Gaoshuai Zhang
Xiangxing Meng
Xinxin Wang
Jiao Xie
Shaoshu Wang
Biao Wang
Jilite Wang
Suwen Liu
Qun Huang
Xu Yang
Jing Li
Hao Wang
author_facet Meijing Zhang
Gaoshuai Zhang
Xiangxing Meng
Xinxin Wang
Jiao Xie
Shaoshu Wang
Biao Wang
Jilite Wang
Suwen Liu
Qun Huang
Xu Yang
Jing Li
Hao Wang
author_sort Meijing Zhang
collection DOAJ
description Hyperoside and quercetin are similar in molecular structures. In this study, the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor (erythroid-2-derived)-related factor 2 (Nrf2) pathway predicted by network pharmacology. And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H2O2-induced HepG2 cells and Caenorhabditis elegans. The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage, which was proved by improved cell viability, decreased reactive oxygen species (ROS) production, decreased cellular apoptosis, and alleviated mitochondrial damage. In addition, quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated mRNAs, increasing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and reducing the cellular malondialdehyde (MDA) content. Quercetin was superior to hyperoside in prolonging the lifespan of worms, decreasing the accumulation of lipofuscin, inhibiting ROS production, and increasing the proportion of skn-1 in the nucleus. With the Nrf2 inhibitor ML385, we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway. Furthermore, molecular docking and dynamics simulations demonstrated that the quercetin- Kelch-like ECH-associated protein 1 (Keap1) complex was more stable than the hyperoside-Keap1 complex. The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role. Overall, quercetin had a better antioxidant than hyperoside.
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spelling doaj-art-6d3bff6617cb4d3bb40eef6ba7352fa82025-01-10T06:56:47ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-07-011341864187610.26599/FSHW.2022.9250155Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and HyperosideMeijing Zhang0Gaoshuai Zhang1Xiangxing Meng2Xinxin Wang3Jiao Xie4Shaoshu Wang5Biao Wang6Jilite Wang7Suwen Liu8Qun Huang9Xu Yang10Jing Li11Hao Wang12State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaState Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaState Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaState Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, ChinaCollege of Chemical Engineering and Materials Science, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaCollege of Chemical Engineering and Materials Science, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaDepartment of Agriculture, Hetao College, Bayannur 015000, ChinaCollege of Food Science & Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066004, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, ChinaNational Center of Supervision and Inspection for Processed Food Quality, Tianjin Institute for Food Safety Inspection Technology, Tianjin 300457, ChinaState Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaState Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, ChinaHyperoside and quercetin are similar in molecular structures. In this study, the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor (erythroid-2-derived)-related factor 2 (Nrf2) pathway predicted by network pharmacology. And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H2O2-induced HepG2 cells and Caenorhabditis elegans. The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage, which was proved by improved cell viability, decreased reactive oxygen species (ROS) production, decreased cellular apoptosis, and alleviated mitochondrial damage. In addition, quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated mRNAs, increasing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and reducing the cellular malondialdehyde (MDA) content. Quercetin was superior to hyperoside in prolonging the lifespan of worms, decreasing the accumulation of lipofuscin, inhibiting ROS production, and increasing the proportion of skn-1 in the nucleus. With the Nrf2 inhibitor ML385, we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway. Furthermore, molecular docking and dynamics simulations demonstrated that the quercetin- Kelch-like ECH-associated protein 1 (Keap1) complex was more stable than the hyperoside-Keap1 complex. The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role. Overall, quercetin had a better antioxidant than hyperoside.https://www.sciopen.com/article/10.26599/FSHW.2022.9250155hyperosidequercetinhepg2 celloxidative damagenrf2 signalling pathway
spellingShingle Meijing Zhang
Gaoshuai Zhang
Xiangxing Meng
Xinxin Wang
Jiao Xie
Shaoshu Wang
Biao Wang
Jilite Wang
Suwen Liu
Qun Huang
Xu Yang
Jing Li
Hao Wang
Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside
Food Science and Human Wellness
hyperoside
quercetin
hepg2 cell
oxidative damage
nrf2 signalling pathway
title Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside
title_full Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside
title_fullStr Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside
title_full_unstemmed Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside
title_short Reduction of the oxidative damage to H2O2-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside
title_sort reduction of the oxidative damage to h2o2 induced hepg2 cells via the nrf2 signalling pathway by plant flavonoids quercetin and hyperoside
topic hyperoside
quercetin
hepg2 cell
oxidative damage
nrf2 signalling pathway
url https://www.sciopen.com/article/10.26599/FSHW.2022.9250155
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