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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
Nutrients · 2023
The consumption of foods that are rich in phenolic compounds has chemopreventive effects on many cancers, including breast cancer, ovarian cancer, and endometrial cancer. A wide spectrum of their health-promoting properties such as antioxidant, anti-inflammatory, and anticancer activities, has been demonstrated. This paper analyzes the mechanisms of the anticancer action of selected common flavonols, including kemferol, myricetin, quercetin, fisetin, galangin, isorhamnetin, and morin, in preclinical studies, with particular emphasis on in vitro studies in gynecological cancers and breast cancer. In the future, these compounds may find applications in the prevention and treatment of gynecological cancers and breast cancer, but this requires further, more advanced research.
Molecular neurobiology · 2023
Neurological diseases place a substantial burden on public health and have a serious impact on the quality of life of patients. Despite the multifaceted pathological process involved in the occurrence and development of these neurological diseases, each disease has its own unique pathological characteristics and underlying molecular mechanisms which trigger their onset. Thus, it is unlikely to achieve effective treatment of neurological diseases by means of a single approach. To this end, we reason that it is pivotal to seek an efficient strategy that implements multitherapeutic targeting and addresses the multifaceted pathological process to overcome the complex issues related to neural dysfunction. In recent years, natural medicinal plant-derived monomers have received extensive attention as new neuroprotective agents for treatment of neurological disorders. Fisetin, a flavonoid, has emerged as a novel potential molecule that enhances neural protection and reverses cognitive abnormalities. The neuroprotective effects of fisetin are attributed to its multifaceted biological activity and multiple therapeutic mechanisms associated with different neurological disorders. In this review article, we summarize recent research progression regarding the pharmacological effects of fisetin in treating several neurological diseases and the potential mechanisms.
Current pharmaceutical biotechnology · 2024
Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function. This systematic review study investigated fisetin's effects and possible mechanisms in attenuating myocardial, cerebral, renal, and hepatic IRIs. This systematic review included studies earlier than Sep 2023 by following the PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords, bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, were used to search the relevant studies. Studies were imported in End- Note X8, and the primary information was recorded in Excel. Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by activating phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases). It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial function, anti-apoptotic effects, promoting autophagy, and preserving tissues from histological changes induced by IRIs. Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal, and hepatic IRIs without any significant side effects.
Nutrients · 2024
Polyphenols are plant metabolites with potential anti-inflammatory and anti-proliferative effects, which may be advantageous for disorders like colorectal cancer (CRC). Despite promising in vitro and in vivo evidence, human clinical trials have yielded mixed results. The present study aimed to evaluate the clinical evidence of polyphenols for CRC prevention or treatment. A systematic review was performed according to PRISMA. Based on a PROSPERO registered protocol (CRD42024560044), online databases (PubMed and COCHRANE) were utilized for the literature search. A total of 100 studies articles were initially identified. After reviewing, 12 studies with a low risk of bias were selected, examining the effect of a variety of compounds. Curcumin demonstrated promise in various trials, mainly decreasing inflammatory cytokines, though results varied, and it did not lower intestinal adenomas or improve outcomes after chemotherapy. Neither epigallocatechin gallate nor artepillin C reduced the incidence of adenomas. Finally, fisetin seemed to improve the inflammatory status of patients under chemotherapy (5-fluorouracil). In summary, although certain polyphenols appear to exert some effect, their role in the prevention or treatment of CRC is inconclusive, and more clinical studies under more controlled conditions are needed.
Current diabetes reviews · 2026
Kidney diseases cause high morbidity and mortality worldwide. This study investigated the mechanistic effects of Fisetin (FIS) on nephrotoxicity, kidney injury, and nephropathy induced by drugs, toxic chemicals, diabetes, lupus, diet, ureteral obstruction, and ischemic situations. To identify pertinent articles published before Oct 1, 2024, a comprehensive electronic search was performed across several databases, including MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, and Scopus. After establishing clear inclusion and exclusion criteria, studies that met the research objectives were selected. Data were extracted and analyzed, documenting study characteristics, methodologies, and biological mechanisms. Antioxidant benefits were evident with increased levels of endogenous antioxidant enzymes and NQO1, alongside reduced oxidative stress markers such as 8-OHdG and MDA. Enhanced mitochondrial function, including improved respiration, ATP synthesis, and antioxidant capacity, further supported cellular resilience. Anti-inflammatory effects were marked by reduced pro-inflammatory cytokines, macrophage and neutrophil infiltration, and inhibited pathways like NF-κB and MAPK. Anti-apoptotic actions included decreased levels of pro-apoptotic proteins. FIS also reduced fibrotic markers and pathways such as TGF-β/SMAD, mitigating excessive ECM buildup. Additionally, modulation of metabolic pathways was observed, including decreased glucose and lipid profiles and improved insulin sensitivity. Kidney function and structural integrity were preserved with reduced levels of nephrotoxic agents. Preclinical studies revealed that FIS demonstrates promising protective effects against kidney toxicity, renal injury, diabetes, and lupus-induced nephropathy. However, more clinical studies are needed in this field to determine effective and safe doses.
Nutrients · 2026
Objective: This double-blind, parallel-group randomized controlled trial is the first to investigate the synergistic effects of interval resistance plus progressive aerobic training with fisetin supplementation on adipokines in obesity. Methods: Sixty sedentary men with obesity (BMI < 30 kg/m2) completed 12 weeks of thrice-weekly interval resistance training (eight exercises, 3 × 13 reps at 60% 1RM with 20% 1RM active rest), immediately followed by staged aerobic bouts (50-70% HRmax). Participants were randomized into the control-placebo (P), fisetin (F; 200 mg/day), training-placebo (TP), or training + fisetin (TF) groups. The primary outcomes were asprosin, MCP-1, and adiponectin; secondary outcomes included leptin and lipid profile. Data were analyzed via ANCOVA with Bonferroni post hoc tests. Results: Statistical analyses were conducted following the intention-to-treat (ITT) principle using an analysis of covariance (ANCOVA) model, which revealed extensive effects of the interventions on the participants' anthropometric and biochemical indices. Regarding body composition, after adjusting for baseline values, a significant difference in mean body weight was observed between groups (F (3, 55) = 9.444, p < 0.001, ηp2 = 0.340); Bonferroni post hoc tests confirmed that the training plus fisetin (TF), training-placebo (TP), and fisetin (F) groups all achieved significant weight loss compared to the placebo (P) group. Furthermore, body mass index (BMI) showed a significant inter-group difference (p = 0.021), with post hoc analysis revealing that only the TF group reached a statistically significant reduction compared to the placebo (p = 0.024; 95% CI [-3.760, -0.172]). In the assessment of biochemical and inflammatory variables, the interventions exerted a highly significant effect on asprosin (F (3, 55) = 36.047, p < 0.001; ηp2 = 0.663) and MCP-1 (F (3, 55) = 29.570, p < 0.001; ηp2 = 0.617). The findings indicated that the TF group experienced the most substantial reductions in both asprosin (-60.71%) and MCP-1 (-46.50%) levels. Regarding adipokines, significant increases in adiponectin levels were observed in the TP (29.38%) and TF (27.67%) groups (p < 0.05), whereas changes in leptin were statistically significant only in the TF group relative to the placebo (p = 0.049). The lipid profile results indicated a statistically significant difference in the TF group in improving all markers; this group achieved greater reduction compared to other groups, including reductions in LDL-C, triglycerides (TG), and total cholesterol (TC) (p < 0.001), while simultaneously showing a significant elevation in HDL-C. Post hoc analyses confirmed robust statistical differences in all lipid parameters for both the TF and TP groups compared to the placebo group (p < 0.05), whereas the placebo group experienced a deterioration in status characterized by a significant increase in LDL-C (p = 0.027) and a significant decline in HDL-C concentrations (p = 0.006). Conclusions: In conclusion, 12 weeks of combined interval resistance-aerobic training and fisetin supplementation significantly reduced pro-inflammatory adipokines and improved lipid profiles in obese men. These findings suggest that asprosin serves as a potential modulator in metabolic risk reduction; however, since direct mechanistic assays were not conducted, these implications remain hypothetical. Future research employing molecular readouts is warranted to confirm the underlying pathways involved.
Diabetes, obesity & metabolism · 2026
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women, associated with insulin resistance, hyperandrogenism, and menstrual irregularities. Nutraceutical interventions-bioactive compounds derived from foods or supplements that provide health benefits beyond basic nutrition-may support conventional therapy. This study aimed to systematically evaluate the effects of nutraceutical interventions on reproductive and metabolic outcomes in PCOS. This systematic review and meta-analysis was registered in PROSPERO (CRD42024521879) and followed PRISMA 2020. Searches were performed in PubMed, Embase, Cochrane Library, Web of Science, and regional databases (January 2013-December 2024) and included 78 eligible studies. Eligible randomized and quasi-experimental studies assessed nutraceuticals such as vitamin D, inositol, and quercetin. Risk of bias was evaluated with standardized tools; certainty of evidence was graded by GRADE. Seventy-eight studies met inclusion criteria. Nutraceutical interventions significantly reduced fasting insulin (MD = -2.14 μIU/mL; 95% CI -3.12 to -1.16) and luteinizing hormone (MD = -1.34 mIU/mL; 95% CI -2.10 to -0.58) and increased sex-hormone-binding globulin (MD = +3.72 nmol/L; 95% CI 1.35 to 6.09). Vitamin D supplementation showed the strongest metabolic and hormonal improvements. Results for ovarian follicle count and menstrual bleeding were inconsistent. Nutraceutical interventions targeting metabolic and hormonal regulation may complement lifestyle therapy in women with PCOS. Interpretation is limited by study heterogeneity and variable methodological quality. No external funding was received.
Frontiers in bioscience (Landmark edition) · 2025
Hepatocellular carcinoma (HCC) is as the most frequently observed histological subtype among primary liver malignancies. While quercetin (QT) shows potential antitumor activity, its preclinical anti-HCC effects and safety (especially in animals) remain unclear. Most existing studies use single methods (e.g., individual animal or in vitro assays), which compromises the reliability of the conclusions. This study's novelty lies in its use of a combined approach-integrating meta-analysis to quantify efficacy and network pharmacology to explore mechanisms, with experimental validation-to address this research gap. This work explores QT's preclinical anti-HCC effects and adverse effects using this integrated approach. We collected literature on the treatment of HCC with QT from January 2000 to August 2024. Nine articles meeting the requirements were included in the current study. Subsequent to this, a meta-analysis was conducted, with further validation via network pharmacology approaches and experimental assays. A meta-analysis found that QT significantly inhibited HCC growth (reduced tumor volume/weight) and reduced mortality in tumor-bearing mice, with no significant effect on body weight. Network pharmacology identified protein kinase B alpha (AKT1) and the phosphoinositide 3-kinase (PI3K)/AKT pathway as potential therapeutic targets. Finally, the aforementioned conclusions were further verified through experimental validation. Preclinically, QT effectively inhibited HCC growth and reduced mortality in tumor-bearing mice without affecting body weight, likely via the PI3K/AKT pathway (targeting AKT1). Our study results furnish preliminary evidence for QT as a promising candidate for HCC adjuvant treatment, supporting its further evaluation in clinical trials. Limitations include reliance on preclinical data; thus, the translational value needs clinical validation, and the underlying mechanisms require more in-depth investigation.
Journal of biochemical and molecular toxicology · 2025
Lipid metabolic disorders, driven by oxidative stress, lipid peroxidation, and chronic inflammation, are key contributors to toxicological damage underlying Nonalcoholic fatty liver disease (NAFLD), atherosclerosis, and metabolic syndrome. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway, a master regulator of antioxidant and detoxification responses, plays a critical role in mitigating cellular toxicity and maintaining lipid homeostasis. A multidisciplinary approach was applied to uncover the molecular toxicology of NRF2 in lipid metabolism. Transcriptomic meta-analysis of GEO datasets identified differentially expressed NRF2-regulated genes in lipid-associated chronic liver diseases (CLD). Clinical meta-analysis synthesized evidence on NRF2 activators and their effects on lipid-related toxic endpoints. Network pharmacology was used to map overlapping targets between NRF2 activation and lipid toxicity, while molecular docking assessed the binding potential of NRF2 activators with KEAP1, a negative regulator of NRF2. Transcriptomic analysis revealed widespread dysregulation of NRF2-dependent antioxidant genes such as GPX4, HMOX1, and NQO2, with 3178 DEGs significantly associated with oxidative stress, ferroptosis, and glutathione metabolism. Clinical meta-analysis demonstrated that NRF2 activators reduced toxic lipid parameters, including triglycerides (↓ 21.81%), LDL (↓ 18.36%), and total cholesterol (↓ 14.15%). Network pharmacology identified 985 overlapping genes linking NRF2 activation to oxidative stress, lipid peroxidation, and fatty acid metabolism. Sixteen natural and synthetic NRF2 activators were highlighted, with molecular docking showing strong KEAP1 binding by quercetin (-9.2 kcal/mol) and luteolin (-9.2 kcal/mol), consistent with disruption of KEAP1-NRF2 interactions and detoxification pathway activation. This integrative molecular toxicology study establishes NRF2 as a central regulator at the interface of oxidative stress and lipid metabolism. Both natural and synthetic NRF2 activators mitigate toxic lipid accumulation and oxidative injury, supporting NRF2 modulation as a promising strategy for preventing and treating lipid metabolic disorders such as NAFLD, atherosclerosis, and metabolic syndrome.
Frontiers in pharmacology · 2025
Quercetin is a naturally occurring flavonoid widely present in fruits, vegetables and tea with multiple pharmacological activities, including immunomodulatory, anti-allergic, antioxidant and anti-inflammatory properties. Preclinical studies have indicated the potential to ameliorate allergic symptoms in animal models, but comprehensive synthesis is still scarce. This meta-analysis was conducted to summarize the therapeutic effects of quercetin in allergic disease models and explore its potential mechanisms. According to PRISMA recommendations, preclinical studies were extracted from PubMed, Web of Science and Embase databases. Thirteen eligible studies were extracted for quantitative synthesis analysis. In total, 13 studies using murine models (BALB/c, C57BL/6 mice, SKH-1 hairless mice and NC/Nga mice; Wistar and Sprague-Dawley rats) were included. The most closely related biomarkers were total IgE, OVA-specific IgE, histamine, inflammatory cytokines (IL-4, IL-5, IL-10, TNF-α, IFN-γ), and immune cell populations (macrophages, lymphocytes, eosinophils, neutrophils). Review Manager 5.4 software was used for analysis, and standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated under a random-effects model. The meta-analysis showed that quercetin significantly decreased the expression of total IgE, OVA-specific IgE, and histamine, and suppressed the infiltration of eosinophils, macrophages, and lymphocytes. Cytokine profiling showed that quercetin significantly suppressed the expression of IL-4 and TNF-α, and increased the expression of IFN-γ, which may contribute to the underlying anti-inflammatory mechanism of quercetin through Th1/Th2 immune rebalancing. Quercetin exhibits strong anti-allergic effects in preclinical models through suppression of IgE, modulation of immune cells, regulation of cytokine network, and reduction of histamine. However, large inter-study heterogeneity and methodological limitations in original studies should be cautiously interpreted. Application in clinical settings should be carefully evaluated through well-designed trials to validate safety, efficacy, and molecular mechanisms in human populations.
Inflammopharmacology · 2026
Diabetes mellitus (DM) is associated with severe complications driven by chronic inflammation, which releases cytokines, chemokines, and adhesion molecules. Herbal medicines are gaining importance due to fewer drug-related adverse effects. Quercetin is a flavonoid with potent anti-inflammatory and antioxidant properties. This systematic review and meta-analysis aim to evaluate the impact of Quercetin on inflammatory markers in the animal model of diabetes. A comprehensive literature search was conducted in PubMed, Embase, Web of Science and Google Scholar from inception to February 2025, to identify relevant preclinical studies. Diabetic rodents were included, whereas in vitro, ex vivo, and non-rodent studies were excluded. A meta-analysis using a random-effects model (RE) was performed to calculate standardised mean differences (SMD) with 95% confidence intervals. Methodological quality was assessed by sensitivity analyses, publication bias and SYRCLE risk of bias. The included 14 studies in this systematic literature review and meta-analysis indicates that Quercetin treatment significantly reduces the TNF-α (SMD: - 3.40, 95% CI - 5.17 to - 1.63) (P = 0.0002), IL-1β (SMD: - 1.57, 95% CI - 2.65 to - 0.49) (P = 0.004) and IL-6 (SMD: - 4.28, 95% CI - 5.86 to - 2.70) (P < 0.00001). Possible publication bias and moderate-to-substantial heterogeneity (I2) were observed. The results remained unchanged after sensitivity analyses, trim-and-fill analyses. The present meta-analysis demonstrates that Quercetin treatment significantly reduces the inflammatory markers in diabetic animal models. These findings provide a strong preclinical foundation for further clinical research, highlighting Quercetin as a potential treatment to mitigate inflammation-driven complications in diabetes.
Drug design, development and therapy · 2025
Spray drying is extensively utilized in pharmaceutical development because of its scalability, cost-effectiveness, and capacity to customize solid-state characteristics. This systematic review (PubMed and Scopus, 2021-2025) assesses the impact of spray drying on the bioavailability and stability of active pharmaceutical ingredients (API) and natural products within solid dispersions (SD), solid self-nanoemulsifying drug delivery systems (S-SNEDDS), and microencapsulation. A total of 27 qualifying studies were identified and offered quantitative comparisons with untreated controls. SDs yielded AUC enhancements of 9-20-fold (eg, oxyberberine approximately 9-fold, quercetin approximately 20-fold) and dissolution improvements of 2-6-fold. S-SNEDDS produced AUC enhancements of 4-9.9-fold (sorafenib approximately 4.6-fold, enzalutamide approximately 7-fold, niclosamide approximately 9.9-fold). Microencapsulation enhanced oxidative stability (eg, approximately 3-fold reduction in peroxide value pepper seed oil and encapsulation efficiency of pomegranate seed oil reaching 90%). Benefits were contingent upon the carrier, especially with PVP/PVPVA, HPMC/HPMCAS, soluplus, and maltodextrin with protein systems. Spray drying provides superior scalability and particle engineering control compared to freeze or vacuum drying, while it still poses hazards of thermal and oxidative stress. Ongoing deficiencies encompass inadequate carrier comparisons, insufficient mechanistic comprehension of drying kinetics, and issues related to scale-up and regulation. This review offers mechanistic insights and a standardized approach to facilitate future formulation development.
Nutrients · 2025
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by persistent inflammation and oxidative stress. Ilex paraguariensis (yerba mate) contains bioactive compounds-particularly chlorogenic acids, quercetin, and rutin-with documented antioxidant and anti-inflammatory properties. Objectives: To systematically review the mechanistic and clinical evidence on Ilex paraguariensis and its main constituents in RA-relevant inflammatory, oxidative, and bone metabolic pathways. Methods: Following PRISMA 2020, PubMed/MEDLINE, LILACS, and SciELO were searched up to September 2025. Eligible studies included yerba mate preparations (last 10 years) or isolated compounds (last 5 years) assessing RA-relevant clinical, inflammatory, oxidative, or bone metabolic outcomes. Non-original studies were excluded. Owing to heterogeneity, findings were narratively synthesized, and risk of bias was evaluated using RoB 2, ROBINS-I, OHAT, and SYRCLE. Results: Twenty-three studies met inclusion criteria: 11 human (clinical or observational), 7 human-based in vitro, and 5 animal studies. Interventions with yerba mate infusions or standardized extracts suggest reductions in inflammatory markers (e.g., C-reactive protein, interleukin-6) and indicate improvements in glutathione-related oxidative balance. Evidence from isolated compounds, particularly quercetin and rutin, suggests comparable anti-inflammatory and antioxidant effects. Preclinical studies appear to indicate modulation of inflammatory and redox pathways relevant to RA. Conclusions: Yerba mate and its constituents show preliminary indications of anti-inflammatory and antioxidant effects with potential relevance to RA pathophysiology. However, in the absence of clinical trials in RA patients, conclusions remain tentative, constrained by small sample sizes, methodological heterogeneity, species differences, and internal validity concerns. Future research should include rigorously designed randomized trials and mechanistic studies using advanced human-relevant platforms, such as organoids and organ-on-chip systems.
Biochimica et biophysica acta. Reviews on cancer · 2026
Ferroptosis, an iron-dependent regulated cell death mechanism driven by lipid peroxidation, offers a novel therapeutic approach for cancer treatment. Flavonoids, a diverse group of polyphenolic compounds, demonstrate significant anticancer potential by modulating ferroptosis pathways, including iron metabolism, GPX4 inhibition, and lipid peroxidation. This study examines flavonoid-induced ferroptosis mechanisms and their therapeutic applications. A systematic review of preclinical and clinical studies evaluated flavonoid effects (quercetin, baicalein, luteolin) on ferroptosis in cancer models. Key mechanisms analyzed included iron pool modulation, GPX4/System Xc- inhibition, and lipid peroxidation enhancement. Synergistic interactions with chemotherapy, immunotherapy, and radiotherapy were assessed. Flavonoids trigger ferroptosis by (1) elevating labile iron to form redox-active complexes that can disrupt homeostasis and amplify Fenton reactions, (2) suppressing GPX4 and System Xc- leading to glutathione depletion and ROS elevation, and (3) upregulating ACSL4/LOX to intensify lipid peroxidation. Preclinical data confirm efficacy in resistant cancers (triple-negative breast cancer, glioblastoma, pancreatic adenocarcinoma) and synergy with standard therapies. Challenges like poor bioavailability and tumor heterogeneity highlight the need for advanced delivery systems (nanoparticles, prodrugs). Flavonoids are promising ferroptosis inducers for apoptosis-resistant cancers, leveraging multi-target mechanisms and emerging delivery technologies. Future research should prioritize clinical translation, biomarker identification, and optimized combination regimens to enhance therapeutic outcomes.
Expert reviews in molecular medicine · 2026
Digestive system cancers (DSCs) constitute a significant number of cancer cases and are closely associated with modifiable risk factors. This umbrella review synthesizes evidence from meta-analyses on the association between dietary polyphenol consumption and the risk of DSCs, addressing limitations in the literature and identifying optimal polyphenol types and doses. Following Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Scopus and Web of Science until April 2025, using specific keywords related to polyphenols and DSCs. Eligible studies included meta-analyses that examined polyphenol intake and DSC risk. The quality was assessed via the AMSTAR 2 and GRADE framework. Statistical analyses were performed using RStudio, employing random-effects models based on the heterogeneity metrics. Data from six meta-analyses, encompassing 27 effect sizes, revealed a statistically significant 11% reduction in the risk of DSCs associated with polyphenol consumption (RR: 0.89; 95% CI: 0.85-0.93; I2: 63%). Subgroup analysis revealed significant risk reductions for specific polyphenol classes: flavonols (22%), quercetin (22%), anthocyanidins (16%), flavan-3-ols (12%) and isoflavones (9%). Publication bias was evident, but adjustments using the trim-and-fill method still indicated a 13% overall reduction in risk (RR: 0.87; 95% CI: 0.83-0.92; I2: 64%). Our findings support the protective role of dietary polyphenols against DSCs, particularly flavonols and quercetin, suggesting that further investigations into the optimal intake levels and mechanisms of action are needed. These findings underscore the potential of dietary modification as a strategy for DSC prevention.
Journal of health, population, and nutrition · 2026
Quercetin, has been proposed as a supplement to improve uric acid -related indices. However, finding supporting evidence remains inconsistent. This meta-analysis aimed to assess the effects of quercetin supplementation on lipid profile, renal function indices, oxidative stress, and inflammatory biomarkers. A systematic review of PubMed, Web of Science, Embase, China Knowledge Network, China Science and Technology Journal Database, and Wanfang Data Knowledge Service Platform from inception to August 2024 were searched. Data were pooled using a random-effects model. Seventeen case studies were included. Quercetin supplementation significantly reduced serum uric acid (UA), creatinine (Cr), fractional excretion of uric acid (FEur), and blood urea nitrogen (BUN) levels, and improved oxidative stress and inflammatory markers, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-a) (p < 0.05). Improvements were also observed in lipid parameters such as triglycerides (TG) and very-low density lipoprotein (VLDL) (p < 0.05). Subgroup analyses indicated that dose and intervention duration influenced outcomes, but the direction and magnitude varied by specific biomarker. However, quercetin supplementation did not have significant effect on urinary UA, urinary Cr, and low density lipoprotein-cholesterol (LDL-C) (p > 0.05). Our findings suggest that quercetin has the potential to improve key biochemical markers, including SUA, VLDL, TNF-α, TG, SOD, Cr, BUN, MDA, IL-6, and FEur, in animal models of hyperuricemia. However, due to high heterogeneity across studies and varying risk of bias, these results should be interpreted cautiously.
International journal of molecular sciences · 2026
Atherosclerosis seriously endangers human health. Quercetin has drawn attention for its potential anti-atherosclerotic pharmacological effects. This study aimed to comprehensively assess quercetin's effect and potential mechanism in treating atherosclerosis through a systematic review and meta-analysis. Preclinical studies published before 20 January 2025 were searched for in databases including PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP. The CAMARADES list was used to assess the quality of the included studies. Stata 12 was applied for overall effect, sensitivity, subgroup, and publication bias analyses. Time-dose interval analyses were conducted to explore how quercetin dose and dosing cycle affect intervention effects. Finally, trial sequential analyses were performed using TSA 0.9 software. A total of 22 studies involving 421 animals were included, with a mean methodological quality score of 7.73/10. Meta-analysis showed that relative to the control group, quercetin reduced aortic plaque area, adjusted lipids (lowered TC, TG, and LDL-C and raised HDL-C), downregulated adhesion factors (e.g., VCAM-1) and pro-inflammatory factors (e.g., IL-1β and IL-6), upregulated anti-inflammatory factor IL-10 and antioxidant enzymes (SOD, CAT) while decreasing MDA content, and regulated atherosclerosis-related targets (e.g., LXRα, SIRT1, and mTOR). Subgroup analyses found model establishment time and quercetin administration time affected aortic lesion areas, TC, and TG. Time-dose analysis indicated quercetin had better ameliorative effects on atherosclerosis at 25-100 mg/kg with an 8-10-week intervention. Quercetin significantly improves atherosclerosis and inhibits its occurrence and progression through multiple pathways, such as regulating lipid metabolism, anti-inflammatory effects, and counteracting oxidative stress. Based on current evidence, quercetin is a potential therapeutic agent for treating atherosclerosis.
The Journal of nutrition · 2026
Several risk factors for severe outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccine responsiveness are related to aging and lifestyle-related conditions, like obesity-associated diabetes. Although vaccination reduces the risk of coronavirus disease 2019 symptoms, vaccine responsiveness in older or metabolically impaired individuals remains variable. This study examined the effects of quercetin glycoside (QG), a bioactive compound with anti-inflammatory and antiaging properties, taken before mRNA vaccination in older or metabolically at-risk individuals, focusing primarily on immune responses and secondarily on vaccine-related reactions. In this randomized, double-blind, placebo-controlled, parallel-group study, participants consumed QG or a placebo daily for 4 wk before a mRNA SARS-CoV-2 booster. Each QG capsule contained 280 mg ± 5% of QG complex; 2 capsules were taken per day. Immune profiles were assessed for 3 mo post vaccination. Linear mixed-effects models evaluated changes in antibody titers and antigen-specific T-cell activation, including group, time, and their interaction as fixed effects, with age, sex, and BMI as covariates. A total of 50 participants (QG = 24; placebo = 26) were analyzed. Vaccine-induced antibody responses rose markedly after the booster in both groups, with similar kinetics and magnitudes. No significant differences were found between groups in neutralizing antibody titers or spike-specific immunoglobin G. Likewise, spike-specific cluster of differentiation 4 (CD4+) and CD8+ T-cell responses were comparable. The frequency and intensity of local and systemic vaccine-related reactions were also similar. The QG group showed a slightly lower median peak temperature (37.3°C compared with 37.9°C), though not significant. Oral QG supplementation did not significantly alter vaccine immunogenicity or reactogenicity. A minor numerical trend toward lower temperature responses was observed, but it was not significant. These findings confirm that QG supplementation was well tolerated and highlight the exploratory nature of this trial. This trial was registered at UMIN as UMIN000046945.
Nutrients · 2026
Advanced glycation end products (AGEs) and oxidative stress increase with aging and are implicated in Alzheimer's disease (AD). We developed an anti-glycation blend using LC-MS-based screening and assessed its effects on oxidative and glycation-related biomarkers in humans. Twelve candidate compounds were screened in a BSA-glucose model using LC-MS peptide mapping to quantify lysine glycation and rank inhibitory activity. The top candidates were combined into a three-compound blend (quercetin, rutin, genistein). In a randomized, double-blind, placebo-controlled 3-month trial, older healthy adults (n = 30) and individuals with AD (n = 30) received anti-AGE blend (n = 15 in older group and n = 15 in AD group) or placebo (n = 15 in older group and n = 15 in AD group). Serum malondialdehyde and urinary Nε-(carboxymethyl)lysine were measured pre-post intervention. Pre/post and between-arm comparisons within each population were performed using REML ANOVA with Tukey post hoc tests. Serum MDA (malondialdehyde) and urinary CML (Nε-(carboxymethyl)lysine) were prespecified biomarker outcomes and are reported here as co-primary biomarker endpoints. No formal a priori sample size calculation was performed; the study size was feasibility-based. LC-MS screening identified genistein, quercetin, and rutin as the most consistent inhibitors of glucose-driven BSA glycation. In older healthy adults, serum MDA decreased after anti-AGE supplementation (p < 0.001) and differed from the placebo (p < 0.01), while no change was observed within the placebo group (ns). In the AD cohort, MDA did not change significantly from baseline within either arm (ns), but post-intervention MDA was lower in anti-AGE than in the placebo (p < 0.05). Urinary CML was unchanged in older healthy adults (ns in both arms), whereas in AD, it decreased after anti-AGE supplementation (p < 0.01) and differed from the placebo (p < 0.05). A screening-guided anti-glycation blend supplementation was associated with changes in selected biomarkers in humans: MDA decreased across cohorts, while CML decreased selectively in AD. Larger trials with extended biomarker panels and LC-MS/MS confirmation are warranted.
Frontiers in endocrinology · 2026
Metabolic diseases represent a significant global public health concern, imposing substantial burdens on healthcare systems, economies, and patient quality of life. Current treatments have limitations, underscoring the need for safer alternatives. Quercetin, a natural flavonoid with favorable human tolerability, shows promise for metabolic disorder management. This review critically evaluates the existing evidence on quercetin's role in metabolic disease management, summarizing its pharmacological advancements and clinical data in treating nine metabolic disorders: diabetes mellitus (DM), metabolic dysfunction-associated fatty liver disease (MAFLD), obesity, atherosclerosis, hyperuricemia, gouty arthritis, hyperlipidemia, osteoporosis, and polycystic ovary syndrome (PCOS). We systematically reviewed studies (2003-2025) from Web of Science, PubMed, Science Direct, and CNKI reporting quercetin's effects in metabolic diseases. Quercetin exhibits multifaceted pharmacological activities, including anti-inflammatory, antioxidant, antiapoptotic, hypolipidemic, and hypoglycemic effects. This underpins its therapeutic potential against nine metabolic disorders. Furthermore, emerging nanodelivery systems have demonstrated enhanced bioavailability, stability, and overall efficacy of quercetin while mitigating its dose-dependent toxicity. Quercetin shows considerable promise in the intervention of metabolic diseases. However, current research lacks mechanistic depth, bioavailability enhancement data, and clinical validation Additionally, clinical studies validating its therapeutic efficacy remain scarce. Further mechanistic investigations and randomized controlled trials are imperative to elucidate quercetin's precise mechanisms and substantiate its clinical potential in metabolic disease management.