ArticleAntioxidants (Basel, Switzerland)2021
Apigenin and Luteolin Regulate Autophagy by Targeting NRH-Quinone Oxidoreductase 2 in Liver Cells.
Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Interaction of Ferroptosis and Immune-Mediated Inflammation in Psoriasis.Antioxidants (Basel, Switzerland) · 2026Review
- Quercetin as a multifaceted neuroprotective agent against cerebral ischaemia-reperfusion injury: mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- Fisetin Attenuates Zinc Overload-Induced Hepatotoxicity in Mice via Autophagy-Dependent Nrf2 Activation.International journal of molecular sciences · 2025Article
- Insights into the cellular function and mechanism of action of quinone reductase 2 (NQO2).The Biochemical journal · 2025Review
- Plant Polyphenols as Heart's Best Friends: From Health Properties, to Cellular Effects, to Molecular Mechanisms of Action.International journal of molecular sciences · 2025Review
- Bioactive Molecules from the Invasive Blue CrabMarine drugs · 2025Article
- Bioactive Molecules from the Exoskeleton ofBiomolecules · 2024Article
- Dramatic Suppression of Lipogenesis and No Increase in Beta-Oxidation Gene Expression Are among the Key Effects of Bergamot Flavonoids in Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2024Article
- Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading.International journal of molecular sciences · 2024Review
- Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways.Antioxidants (Basel, Switzerland) · 2024Review
- Comparative Analysis of Two NNMT Bisubstrate Inhibitors through Chemoproteomic Studies: Uncovering the Role of Unconventional SAM Analogue Moiety for Improved Selectivity.ACS chemical biology · 2024Article
- Polymorphisms and Pharmacogenomics ofGenes · 2024Review
- The specific NQO2 inhibitor, S29434, only marginally improves the survival of dopamine neurons in MPTP-intoxicated mice.Journal of neural transmission (Vienna, Austria : 1996) · 2024Article
- Autophagy and neuroprotection in astrocytes exposed to 6-hydroxydopamine is negatively regulated by NQO2: relevance to Parkinson's disease.Scientific reports · 2023Article
- The influence of NQO2 on the dysfunctional autophagy and oxidative stress induced in the hippocampus of rats and in SH-SY5Y cells by fluoride.CNS neuroscience & therapeutics · 2023Article
- Role of Induced Programmed Cell Death in the Chemopreventive Potential of Apigenin.International journal of molecular sciences · 2022Review
- The Unusual Cosubstrate Specificity of NQO2: Conservation Throughout the Amniotes and Implications for Cellular Function.Frontiers in pharmacology · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Dietary flavonoids stimulate autophagy and prevent liver dysfunction, but the upstream signaling pathways triggered by these compounds are not well understood. Certain polyphenols bind directly to NRH-quinone oxidoreductase 2 (NQO2) and inhibit its activity. NQO2 is highly expressed in the liver, where it participates in quinone metabolism, but recent evidence indicates that it may also play a role in the regulation of oxidative stress and autophagy. Here, we addressed a potential role of NQO2 in autophagy induction by flavonoids. The pro-autophagic activity of seven flavonoid aglycons correlated perfectly with their ability to inhibit NQO2 activity, and flavones such as apigenin and luteolin showed the strongest activity in all assays. The silencing of NQO2 strongly reduced flavone-induced autophagic flux, although it increased basal LC3-II levels in HepG2 cells. Both flavones induced AMP kinase (AMPK) activation, while its reduction by AMPK beta (PRKAB1) silencing inhibited flavone-induced autophagy. Interestingly, the depletion of NQO2 levels by siRNA increased the basal AMPK phosphorylation but abrogated its further increase by apigenin. Thus, NQO2 contributes to the negative regulation of AMPK activity and autophagy, while its targeting by flavones releases pro-autophagic signals. These findings imply that NQO2 works as a flavone receptor mediating autophagy and may contribute to other hepatic effects of flavonoids.
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