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Open Access

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

Meijing Zhanga,1, Gaoshuai Zhanga,1, Xiangxing Menga,, Xinxin Wanga, Jiao Xieb, Shaoshu Wangc, Biao Wangc, Jilite Wangd, Suwen Liue( ), Qun Huangb( ), Xu Yangf( ), Jing Lia( ), Hao Wanga( )
State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology (TUST), Tianjin 300457, China
Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, China
College of Chemical Engineering and Materials Science, Tianjin University of Science and Technology (TUST), Tianjin 300457, China
Department of Agriculture, Hetao College, Bayannur 015000, China
College of Food Science & Technology, Hebei Normal University of Science and Technology, Qinhuangdao 066004, China
National Center of Supervision and Inspection for Processed Food Quality, Tianjin Institute for Food Safety Inspection Technology, Tianjin 300457, China

1 These authors contributed equally to this work and should be considered co-first authors.

Peer review under responsibility of Tsinghua University Press.

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Abstract

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.

Keywords

QuercetinHepG2 cellOxidative damageHyperosideNrf2 signalling pathway

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Food Science and Human Wellness
Volume 13 Issue 4,
July 2024
Pages 1864-1876
DOI: 10.26599/FSHW.2022.9250155
Cite this article:
Zhang M, Zhang G, Meng X, et al. 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, 2024, 13(4): 1864-1876. https://doi.org/10.26599/FSHW.2022.9250155

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Received: 14 November 2022
Revised: 04 January 2023
Accepted: 01 February 2023
Published: 20 May 2024
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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