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.

Recent Publications Focus

Below is a summary of the newest research publications targeting quercetin (sorted by publication date).

Recent research has predominantly focused on overcoming quercetin's poor aqueous solubility and bioavailability through advanced nanoformulation strategies. Quercetin combined with nanomicelles demonstrated enhanced efficacy against Mycoplasma gallisepticum infection in broilers, with nanomicelle formulations showing superior pharmacokinetics and reduced MG counts compared to free quercetin [42406229]. Vegetable butter-based nanostructured lipid carriers loaded with quercetin significantly improved wound healing-related cellular effects, with superior performance from shea butter formulations that provided enhanced antioxidant protection by reducing H₂O₂-induced reactive oxygen species [42410212]. A dual-fibril gel delivery system combining tiger-nut protein fibrils with carboxylated cellulose nanofibrils markedly amplified quercetin's intestinal barrier-protective effects in a DSS-induced barrier injury model, preserving mucosal architecture and restoring tight-junction proteins while modulating the gut microbiota [42347739]. Herbosomal nanocarriers using natural-origin betaine surfactants significantly enhanced quercetin's therapeutic potential in aluminum chloride-induced Alzheimer's disease models, demonstrating superior behavioral and biochemical improvements over conventional quercetin suspensions [42191751]. Magnetic ionic liquid nanomicelles and multifunctional nanozyme hydrogels with mesoporous Ce-doped europium oxide further improved quercetin's solubilization and therapeutic efficacy in various disease contexts [42052870, 42128418].

Quercetin demonstrated significant neuroprotective and immunomodulatory effects across multiple neurological conditions. In postoperative cognitive dysfunction, quercetin ameliorated cognitive impairment in aged mice by regulating microglial polarization through ADAR2-mediated editing of miR-379-5p, thereby modulating the GSK3β pathway and alleviating neuroinflammation [42209865]. For ischemic stroke, self-assembled quercetin-mecobalamin nanoparticles markedly reduced infarct size and neuroinflammation at a 1/10 dose compared to free quercetin, modulating anti-inflammatory pathways and suppressing microglial M1 polarization via Panx1 downregulation [42028836]. In spinal cord injury, the nanozyme hydrogel efficiently scavenged reactive oxygen species, inhibited apoptosis, promoted macrophage M2 polarization, and enhanced autophagy/mitophagy markers, culminating in improved locomotor function [42128418].

Quercetin displayed potent anti-inflammatory and metabolic regulatory activities through multiple signaling pathways across diverse disease models. In hepatocellular carcinoma, bioinformatics analysis identified quercetin as a potential multi-target therapeutic agent significantly downregulating five hub genes (RFC4, TOP2A, AURKA, HSP90AA1, MCM4) and inhibiting HepG2 cell viability in a dose-dependent manner [42145839]. In hyperuricemia, quercetin and other flavonoids from Lithocarpus litseifolius reduced serum uric acid levels and ameliorated renal dysfunction by modulating the TLR2/PI3K/NF-κB signaling pathway and altering gut microbiota composition [42132650]. Quercetin treatment alleviated rheumatoid arthritis by downregulating the NLRP3/Caspase-1/GSDMD-mediated pyroptosis pathway [42033182], while in ulcerative colitis, pH-sensitive chitosan-tripolyphosphate/Eudragit® S100 nanoparticles loaded with quercetin significantly reduced inflammatory markers, Th1 cell frequency, and oxidative stress [42025668]. In diabetic liver damage, combined melatonin and quercetin treatment mitigated oxidative stress and inflammatory cytokine expression [42021540]. Notably, in triple-negative breast cancer, co-assembled quercetin and sorafenib nanoparticles synergistically potentiated ferroptosis by suppressing HIF-1α expression and inhibiting glycolysis in acidic tumor microenvironments [41946426].

Multiple studies established quercetin's antimicrobial and antioxidant properties within complex plant extracts and targeted therapeutic applications. Flavonoid compounds including quercetin from Convolvulus oxyphyllus extracts significantly suppressed IL-6 and COX-2 expression, demonstrating anti-inflammatory potential comparable to celecoxib [42128884], while quercetin in Fagonia cretica extract displayed favorable antioxidant and antibacterial activities with strong binding affinities to multiple protein targets [42168772]. Quercetin's geroprotective effects were demonstrated against hydroquinone toxicity in Drosophila, enhancing lifespan, fertility, and reducing gut toxicity [42154051]. In bacterial keratitis treatment, a nanocomposite combining quercetin with mesoporous polydopamine and silver nanoparticles achieved 97.0% antibacterial rate, surpassing levofloxacin eye drops while inhibiting corneal neovascularization [41558272]. For acute kidney injury, a multifunctional RGD-targeted cerium dioxide nanoplatform loaded with quercetin promoted mitophagy and alleviated renal ischemia-reperfusion injury through Nrf2/HO-1/GPX4/SOD1 pathway activation [41506100]. In sepsis, biomimetic platelet-mimicking nanoparticles loaded with quercetin modulated oxidative stress, inflammation, and coagulation imbalance, significantly improving survival [41990977].

Wound healing and controlled-release formulations represented emerging applications for quercetin-based therapeutics. Multilayered electrospun membranes incorporating quercetin-loaded microspheres achieved extended 24-hour drug release and promoted wound healing with enhanced collagen deposition and reduced COX-2 levels [41576605]. chitosan/gelatin/polyvinyl alcohol nanocomposites containing quercetin-loaded magnesium oxide nanoparticles significantly upregulated keratinocyte growth factor 1 (KGF1) expression and accelerated wound closure in murine excisional wound models [41248680]. Advanced co-delivery systems, including ethyl cellulose-zein Janus nanoparticles capable of regionally encapsulating quercetin and curcumin, achieved controlled sequential release in the small intestine and colon during in vitro digestion [41831974].