ArticleRedox biology2016
Quercetin affects glutathione levels and redox ratio in human aortic endothelial cells not through oxidation but formation and cellular export of quercetin-glutathione conjugates and upregulation of glutamate-cysteine ligase.
Article in Redox biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- A Systematic Review: Quercetin-Secondary Metabolite of the Flavonol Class, with Multiple Health Benefits and Low Bioavailability.International journal of molecular sciences · 2024Pooled it
- Exploring Mechanisms of Ephx2 in Treating Atherosclerosis Using Independent Cascade Model and Adverse Outcome Pathways.Combinatorial chemistry & high throughput screening · 2026Article
- SELL Marks an Effector-Deficient CD8Human mutation · 2026Article
- The Potential Application of Nanocarriers in Delivering Topical Antioxidants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Multi-target mechanisms and potential applications of quercetin in the treatment of acne vulgaris.Frontiers in pharmacology · 2025Review
- Quercetin Impairs the Growth of Uveal Melanoma Cells by Interfering with Glucose Uptake and Metabolism.International journal of molecular sciences · 2024Article
- A detailed overview of quercetin: implications for cell death and liver fibrosis mechanisms.Frontiers in pharmacology · 2024Review
- The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates.Antioxidants (Basel, Switzerland) · 2023Review
- Quercetin Reprograms Immunometabolism of Macrophages via the SIRT1/PGC-1α Signaling Pathway to Ameliorate Lipopolysaccharide-Induced Oxidative Damage.International journal of molecular sciences · 2023Article
- The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression.Plants (Basel, Switzerland) · 2022Review
- Sulodexide Increases Glutathione Synthesis and Causes Pro-Reducing Shift in Glutathione-Redox State in HUVECs Exposed to Oxygen-Glucose Deprivation: Implication for Protection of Endothelium against Ischemic Injury.Molecules (Basel, Switzerland) · 2022Article
- Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway.Antioxidants (Basel, Switzerland) · 2022Article
- The Experimental Exploration of TCM Theory "Treating the Same Disease with Different Approaches" on an Ulcerative Colitis Model.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Effect of the flavonoids quercetin and taxifolin on UVA-induced damage to human primary skin keratinocytes and fibroblasts.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2022Article
- Neuroinflammation as a Therapeutic Target in Retinitis Pigmentosa and Quercetin as Its Potential Modulator.Pharmaceutics · 2021Review
- The Potency ofFrontiers in pharmacology · 2021Review
- Chinese Herbal Medicines and Active Metabolites: Potential Antioxidant Treatments for Atherosclerosis.Frontiers in pharmacology · 2021Review
- Modulation of Th1/Th2 Cytokine Balance by Quercetin In Vitro.Medicines (Basel, Switzerland) · 2020Article
- Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury.Molecules (Basel, Switzerland) · 2020Article
- Quercetin Alleviates Intestinal Oxidative Damage Induced by HACS omega · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial dysfunction due to vascular inflammation and oxidative stress critically contributes to the etiology of atherosclerosis. The intracellular redox environment plays a key role in regulating endothelial cell function and is intimately linked to cellular thiol status, including and foremost glutathione (GSH). In the present study we investigated whether and how the dietary flavonoid, quercetin, affects GSH status of human aortic endothelial cells (HAEC) and their response to oxidative stress. We found that treating cells with buthionine sulfoximine to deplete cellular GSH levels significantly reduced the capacity of quercetin to inhibit lipopolysaccharide (LPS)-induced oxidant production. Furthermore, incubation of HAEC with quercetin caused a transient decrease and then full recovery of cellular GSH concentrations. The initial decline in GSH was not accompanied by a corresponding increase in glutathione disulfide (GSSG). To the contrary, GSSG levels, which were less than 0.5% of GSH levels at baseline (0.26±0.01 vs. 64.7±1.9nmol/mg protein, respectively), decreased by about 25% during incubation with quercetin. As a result, the GSH: GSSG ratio increased by about 70%, from 253±7 to 372±23. These quercetin-induced changes in GSH and GSSG levels were not affected by treating HAEC with 500µM ascorbic acid phosphate for 24h to increase intracellular ascorbate levels. Incubation of HAEC with quercetin also led to the appearance of extracellular quercetin-glutathione conjugates, which was paralleled by upregulation of the multidrug resistance protein 1 (MRP1). Furthermore, quercetin slightly but significantly increased mRNA and protein levels of glutamate-cysteine ligase (GCL) catalytic and modifier subunits. Taken together, our results suggest that quercetin causes loss of GSH in HAEC, not because of oxidation but due to formation and cellular export of quercetin-glutathione conjugates. Induction by quercetin of GCL subsequently restores GSH levels, thereby suppressing LPS-induced oxidant production.
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Registered trials
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