quercetin

Overview

Quercetin (Wikidata: Q409478) is a naturally occurring flavonoid belonging to the 2-phenylchromane flavonoid subclass, widely distributed across fruits, vegetables, and medicinal plants including dandelion (Taraxacum officinale), sea buckthorn, pitaya (Selenicereus monacanthus), and Lithocarpus litseifolius. It is among the most extensively studied dietary polyphenols, recognized for a broad spectrum of biological activities encompassing antioxidant, anti-inflammatory, immunomodulatory, anticancer, antiviral, antimicrobial, hepatoprotective, and neuroprotective properties. Chemically, quercetin features a characteristic hydroxyl-substituted flavone backbone that confers its potent free-radical scavenging capacity, enabling it to neutralize reactive oxygen species and modulate redox-sensitive signaling cascades involving nuclear factor erythroid 2-related factor 2 (Nrf2) and oxidative stress pathways.

At the molecular level, quercetin exerts its effects through engagement with multiple biological targets simultaneously, including the PI3K/Akt signaling pathway, TLR4/P2X7-NLRP3 inflammasome pathway, and TP53-mediated apoptotic signaling. Its ability to suppress proinflammatory cytokines such as interleukin-1 beta and interleukin-6, inhibit Prostaglandin-endoperoxide synthase 2 (COX-2), and modulate Gasdermin D-mediated pyroptosis underlies its therapeutic versatility. Despite this pharmacological richness, quercetin's clinical translation has historically been limited by poor aqueous solubility, low oral bioavailability, and rapid metabolic clearance — challenges that have driven extensive recent interest in advanced nanoformulation strategies.

Focus of Latest Publications

Recent investigations have demonstrated quercetin's broad therapeutic potential across multiple disease models, though its clinical translation remains hindered by poor aqueous solubility, low bioavailability, and rapid metabolism. Research has documented quercetin's antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory activities, with substantial effort directed toward overcoming these pharmacokinetic limitations through advanced nanoformulation strategies and combination therapies.

In infectious disease applications, quercetin has shown promise both as a standalone agent and in combination with conventional antimicrobials. Combined with doxycycline in nanomicelle form against Mycoplasma gallisepticum in broilers, nanomicellar quercetin demonstrated superior efficacy to conventional quercetin, improving doxycycline pharmacokinetics, prolonging serum persistence above the minimum inhibitory concentration, and enabling extended dosing intervals while maintaining favorable tissue depletion profiles. Quercetin was also identified as a bacterial neuraminidase inhibitor and as a component of plant extracts with broad-spectrum antibacterial activity. In bacterial keratitis models, quercetin-loaded mesoporous polydopamine nanocomposites achieved 97% bacterial eradication, exceeding levofloxacin efficacy, while simultaneously demonstrating anti-angiogenic activity and reduced corneal opacity.

Quercetin has emerged as a multi-target therapeutic agent in cancer and inflammatory diseases through mechanisms targeting critical signaling pathways. In hepatocellular carcinoma, integrated bioinformatics and experimental studies identified quercetin as a potential inhibitor of five hub genes (RFC4, TOP2A, AURKA, HSP90AA1, MCM4) implicated in cell-cycle, p53, and FoxO signaling pathways, with molecular docking confirming binding energies below −5 kcal/mol. In triple-negative breast cancer, quercetin co-assembled with sorafenib enhanced ferroptosis by suppressing hypoxia-inducible factor-1α and hexokinase II, thereby mitigating the tumoral hypoxic and acidic microenvironment that typically confers ferroptosis resistance. Quercetin also regulated the NLRP3/Caspase-1/GSDMD pyroptosis pathway in rheumatoid arthritis models and suppressed IL-6 and COX-2 expression in inflammatory disease contexts, with molecular docking demonstrating strong ligand-target interactions comparable to standard anti-inflammatory drugs.

In neurodegenerative and tissue regeneration applications, quercetin formulations have demonstrated significant neuroprotective and regenerative benefits. A herbosomal quercetin delivery system using natural-origin betaine surfactants showed superior efficacy in aluminum chloride-induced Alzheimer's disease models compared to quercetin suspension. In postoperative cognitive dysfunction, quercetin ameliorated cognitive impairment by regulating microglial polarization through ADAR2-mediated editing of miR-379-5p, redirecting the RNA modification target from PANK1 to GSK3β and thereby modulating inflammatory signaling. A quercetin-mecobalamin nanoparticle formulation reduced infarct size and improved functional recovery in ischemic stroke models at a 1/10 dose of free quercetin through downregulation of Panx1 and pro-inflammatory cytokine production. For wound and tissue repair, quercetin-loaded multilayered electrospun membranes achieved sustained dual-drug release over 24 hours with upregulated antioxidant metabolites and enhanced collagen deposition, while quercetin-MgO nanoparticles in chitosan/gelatin/polyvinyl alcohol matrices accelerated wound closure through KGF1 upregulation and dose-dependent fibroblast activation.

Across these diverse therapeutic contexts, nanoformulation of quercetin—whether as nanomicelles, herbosomes, Janus nanoparticles, metal-phenolic complexes, or mesoporous carriers—consistently improved cellular uptake, pharmacokinetic profiles, and therapeutic efficacy compared to free quercetin. Mechanistically, quercetin operates through multiple pathways including the Nrf2/HO-1/GPX4/SOD1 axis for oxidative stress mitigation, TLR2/PI3K/NF-κB inhibition for hyperuricemia management, and cholesterol-driven mitochondrial rejuvenation via lipid raft remodeling in diabetes-related complications. These delivery innovations, combined with the elucidation of quercetin's multi-target molecular mechanisms, position advanced nanoformulations as promising candidates for translating quercetin's broad therapeutic potential into clinical applications across infectious, oncologic, inflammatory, and degenerative disease contexts.

Key Publications

• NEWJun Biomedical publication details. (PubMed Database, 2026, PMID 42406229)
• May Quercetin Alleviates Postoperative Cognitive Dysfunction of Aged Mice by Regulating Microglial Polarization through Inducing miR-379-5p RNA Modification. (Molecular neurobiology, 2026, PMID 42209865): "Quercetin is a multifunctional natural active ingredient with significant potential in antioxidation, anti-inflammatory and neuroprotection."
• May Herbosomal nanocarriers using natural-origin surfactants: a quercetin-based strategy for Alzheimer's disease and oxidative-stress-driven neurodegeneration. (Scientific reports, 2026, PMID 42191751): "Quercetin (QUE) is a multifunctional flavonoid with potent antioxidant and anti-inflammatory effects and proven neuroprotective, anticancer, antimicrobial, and hepatoprotective potential."
• May Systematic identification of bacterial neuraminidase inhibitors from Psoralea corylifolia using ultrafiltration-UPLC-Q-Orbitrap-MS and molecular dynamics. (Journal of enzyme inhibition and medicinal chemistry, 2026, PMID 42179005): "...more active than the positive control, quercetin (IC50 = 13.63 ± 1.05 μM)."
• Jun Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Profiling, Antioxidant, Antibacterial, and Antidiabetic Properties of Fagonia cretica L.: Insights From In Vitro and In Silico Approaches. (ChemistryOpen, 2026, PMID 42168772): "Molecular docking identified quercetin, luteolin, and catechin as leading compounds, displaying strong binding affinities across antioxidant, antibacterial, and antidiabetic protein targets-at times surpassing reference ligands."
• May Geroprotective effects of bioactive compounds against hydroquinone toxicity in Drosophila melanogaster: an in vivo and in silico insight. (Biogerontology, 2026, PMID 42154051): "Our study, explored 2'-hydroxyflavanone (2HF) and quercetin (QE) effects on HQ exposed Drosophila through gut toxicity assays (trypan blue) and survivorship (Kaplan-Meier plots) along with fertility and fecundity of female flies."
• Jun Integrative bioinformatics and experimental validation reveal quercetin as a potential multi-target therapeutic agent in hepatocellular carcinoma. (Cytotechnology, 2026, PMID 42145839): "To validate the computational predictions, a quercetin intervention model was established."
• May Lithocarpus litseifolius leaf extract and its flavonoids alleviate hyperuricemia via TLR2/PI3K/NF-κB pathway inhibition and gut microbiota modulation. (Food & function, 2026, PMID 42132650): "...its flavonoids (isoquercitrin, phlorizin, trilobatin, quercetin, phloretin)..."
• May Multifunctional Nanozyme Hydrogel for Oxidative Stress Scavenging and Mitophagy Activation in Spinal Cord Injury Repair. (ACS applied materials & interfaces, 2026, PMID 42128418): "Here, we report a supramolecular hydrogel, Que@MCEu/H, engineered by metal-phenolic coordination between Quercetin (Que) and mesoporous Ce-doped europium oxide nanozymes (MCEu)."
• May Biogenic selenium extract-mediated and total Convolvulus oxyphyllus extracts suppress IL6 and COX2 expression: insights from LC-MS metabolite profiling and molecular docking. (Scientific reports, 2026, PMID 42128884): "molecular docking to assess the binding interactions of selected most abundant flavonoid compounds (quercetin, daidzein-8-C-glucoside, kaempferol-7-neohesperidoside, and eriodictyol-7-O-neohesperidoside) with COX-2 (PDB ID: 8ET0) and IL-6 (PDB ID: 4N19)."