ArticleMolecules (Basel, Switzerland)2019
Nrf2⁻ARE Signaling Acts as Master Pathway for the Cellular Antioxidant Activity of Fisetin.
Article in Molecules (Basel, Switzerland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- Fisetin attenuates oxidative and haemolytic damage induced by quinuclidine derivatives in human erythrocytes.Arhiv za higijenu rada i toksikologiju · 2026Article
- Sulfation Rewrites the Biological Profile of Dietary Flavonoids: Implications for Stability, Redox Signaling, and Inflammation.Food science & nutrition · 2026Article
- Low-Dose Fisetin Supplementation and Its Association With Chronic Inflammation in Middle-Aged and Older Adults: Study Protocol for a Triple-Blind, Randomised, Placebo-Controlled Trial.Basic & clinical pharmacology & toxicology · 2026Article
- Fisetin attenuates glutamate-induced excitotoxicity and modulates neural progenitor cell dynamics in vitro.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Total Synthesis and Biological Activities of Polyhydroxy Flavonols: A Review.Molecules (Basel, Switzerland) · 2026Review
- Role of Fisetin in the Mammalian Reproductive System.Veterinary sciences · 2026Review
- Review
- Fisetin as a nutritional senotherapeutic: mechanisms, translational promise, and lessons from chronic kidney disease.Frontiers in nutrition · 2026Review
- Wise as a Serpent and Gentle as a Dove: Pharmacological Targeting of NRF2/KEAP1 Pathway from Treasure Trove of Mother Nature.Drug design, development and therapy · 2026Review
- Mechanistic Analysis of Fisetin in Liver Diseases and Its Potential Therapeutic Application in IFALD-A Review of In Vitro and In Vivo Studies.Nutrients · 2025Review
- SenolyticSynergy: An Attention-Based Network for Discovering Novel Senolytic Combinations via Human Aging Genomics.International journal of molecular sciences · 2025Article
- Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition.Aging · 2025Article
- The protective effects of fisetin in metabolic disorders: a focus on oxidative stress and associated events.Journal of diabetes and metabolic disorders · 2024Review
- Natural plant polyphenols contribute to the ecological and healthy swine production.Journal of animal science and biotechnology · 2024Review
- Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway.Molecules (Basel, Switzerland) · 2024Article
- Investigating the role of itaconate in macrophage activation and oxidative stress injury in sepsis-associated acute kidney injury.Molecular biology reports · 2024Article
- Fisetin Alleviates Inflammation and Oxidative Stress in Deep Vein Thrombosis via MAPK and NRF2 Signaling Pathway.International journal of molecular sciences · 2024Article
- Mechanistic insight of curcumin: a potential pharmacological candidate for epilepsy.Frontiers in pharmacology · 2024Review
- Flavonoids Regulate Redox-Responsive Transcription Factors in Glioblastoma and Microglia.Cells · 2023Article
- An Overview of Recent Advances in the Neuroprotective Potentials of Fisetin against Diverse Insults in Neurological Diseases and the Underlying Signaling Pathways.Biomedicines · 2023Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Fisetin, a dietary flavonoid, is reported to have cellular antioxidant activity with an unclear mechanism. In this study, we investigated the effect of fisetin on the nuclear factor, erythroid 2-like 2 (Nrf2) signaling pathway in HepG2 cells to explore the cellular antioxidant mechanism. Fisetin upregulated the mRNA expression of heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase-1 (NQO1), and induced the protein of HO-1 but had no significant effect on the protein of GCLC, GCLM and NQO1. Moreover, nuclear accumulation of Nrf2 was clearly observed by immunofluorescence analysis and western blotting after fisetin treatment, and an enhanced luciferase activity of antioxidant response element (ARE)-regulated transactivation was obtained by dual-luciferase reporter gene assays. In addition, fisetin upregulated the protein level of Nrf2 and downregulated the protein level of Kelch-like ECH-associated protein 1 (Keap1). However, fisetin had no significant effect on Nrf2 mRNA expression. When protein synthesis was inhibited with cycloheximide (CHX), fisetin prolonged the half-life of Nrf2 from 15 min to 45 min. When blocking Nrf2 degradation with proteasome inhibitor MG132, ubiquitinated proteins were enhanced, and fisetin reduced ubiquitination of Nrf2. Taken together, fisetin translocated Nrf2 into the nucleus and upregulated the expression of downstream HO-1 gene by inhibiting the degradation of Nrf2 at the post-transcriptional level. These data provide the molecular mechanism to understand the cellular antioxidant activity of fisetin.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.