Quercetin

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. © 2025. The Author(s).

AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. © 2025 John Wiley & Sons Ltd.

BACKGROUND: The prevalence of obesity among women of reproductive age is increasing worldwide. Obesity significantly increases the risk of adverse pregnancy outcomes. The effectiveness of probiotics in improving the pregnancy outcomes of overweight or obese pregnant women is still controversial. METHODS: PubMed, Embase, Scopus, Cochrane, and Web of Science were searched for relevant articles up to May 30, 2025. Revman 5.4 was used for the meta-analysis. In network pharmacology, the gutMGene database was used to obtain the bioactive components of probiotics, and the SwissTargetPrediction platform was used to predict the targets of the active components. The related targets of diseases were obtained through OMIM and GeneCards databases and the bioactive compound-target network was constructed. AutoDockTools software was used for molecular docking verification. RESULTS: Eight randomized controlled trials (RCTs) involving 1563 participants were included in the meta-analysis.The results showed no significant difference between probiotic and control in improving adverse pregnancy outcomes.However, subgroup analyses indicated that the combination of Bifidobacterium and Lactobacillus significantly reduced the risk of small-for-gestational-age (SGA) (RR = 0.54, 95% CI [0.30,0.96], P = 0.04). Network pharmacology identified 46 bioactive metabolites and 166 targets. The key bioactive metabolites of probiotics were arctigenin, aglycone, 10-Oxo-11-octadecenoic acid, doconexent, 10-keto-12Z-octadecenoic acid, kaempferol, quercetin, ponciretin, caffeic acid, and equol. The core targets were STAT3, ESR1, HSP90AA1, CCND1, AKT1, EGFR, BCL2, SRC, MTOR, and TP53. Molecular docking validated high-affinity interactions. CONCLUSION: These findings suggest that probiotics can improve some adverse pregnancy outcomes in overweight or obese pregnant women through multiple components, targets and pathways, and provide a basis for further research. In the future, more in vitro and in vivo studies are needed to verify the efficacy of probiotics. The study has been registered in the international prospective register of systematic reviews (PROSPERO) under the number CRD42024576090. © 2025. T

BACKGROUND: The therapeutic application of dietary polyphenols in chronic obstructive pulmonary disease (COPD) management represents an emerging therapeutic paradigm in pulmonary medicine. As bioactive compounds exhibiting dual antioxidant and anti-inflammatory properties, polyphenolic derivatives demonstrate significant therapeutic potential through multimodal mechanisms targeting COPD pathophysiology - particularly in modulating redox homeostasis (GSH/GSSG ratio elevation), attenuating NF-κB-mediated inflammatory cascades, and enhancing respiratory function parameters (FEV1 improvement ≥12% from baseline). However, current clinical evidence remains inconclusive, with meta-analyses revealing heterogeneity in intervention outcomes across randomized controlled trials. This systematic investigation employs a triple-blind, placebo-controlled design to rigorously evaluate the clinical efficacy of standardized oral polyphenol supplementation in COPD patients (GOLD stages II-III), incorporating advanced biomarkers including 8-isoprostane quantification and pulmonary function trajectory analysis. METHODS: Literature on dietary polyphenols for the treatment of COPD published in PubMed, Cochrane, Medline, CNKI and other databases before December 26, 2024 (in Chinese and English) was searched. Manual screening, quality assessment and data extraction of search results were performed in strict accordance with the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software. RESULTS: The randomized controlled trials (RCTs) included in this review examined dietary supplementation with eight polyphenols-curcumin, resveratrol, anthocyanins, quercetin, salidroside, dietary beetroot juice, pomegranate juice, and adjunctive oral AKL1 treatment-across a total of 894 participants. This systematic review and meta-analysis revealed that, compared to a placebo; ① Curcumin significantly reduced systolic blood pressure (SBP) and improved FEV1(SMD=-0.82, 95%CI -1.53 to -0.11); ② Salidroside was effective in reducing thrombotic markers (TT, D-D), inflammatory factors (TNF-α) and symptom scores (CAT) (p<0.01); ③ Resveratrol significantly downregulates serum TNF-α

This systematic review evaluated a total of 31 included human intervention studies that have assessed methods to improve quercetin bioavailability from different formulations and food matrices using urine or blood samples up to July 2024. The bioavailability of quercetin in humans was affected by several factors. 1) Chemical structure: Quercetin-3-O-oligoglucosides exhibited 2-fold higher bioavailability than quercetin-3-O-glucoside, 10-fold higher than quercetin-3-O-rutinoside and ∼ 20-fold higher than quercetin aglycone. 2) Modification of physicochemical properties: In comparison to quercetin aglycone, the quercetin-3-O-glucoside-γ-cyclodextrin inclusion complex showed a 10.8-fold increase in bioavailability, while the self-emulsifying fenugreek galactomannans and lecithin encapsulation, and lecithin phytosome, showed a 62- and 20.1-fold increase, respectively. 3) Food matrix effects: the addition of dietary fats and fibre increased bioavailability by ∼2-fold. This review summarises key factors that enhance quercetin bioavailability, contributing to the development of more effective and practical quercetin supplements or functional foods for better bioactivity of quercetin in humans.

The effects of quercetin supplementation on blood pressure (BP) remain unclear. The aim of this meta-analysis is to summarize data focused on quercetin impact on systolic BP (SBP) and diastolic BP (DBP). Medline, EMBASE and Web of Science databases were searched to identify randomized controlled trials that assessed the impact of quercetin on BP until May 2022. A random-effects model was used for data analysis. Subgroup analysis was performed to explore the effects in (pre)hypertensive and normotensive adults. Ten trials (841 participants in total) were included into the analysis. The results showed that quercetin supplementation significantly decreased SBP in the mixed population (MD: -2.38mmHg; 95% CI: -3.80 - -0.96; P = 0.01) and in the normotensive subgroup (MD: -1.82mmHg; 95% CI: -2.43 - -1.20; P < 0.0001) and DBP in the (pre)hypertensive subgroup (MD: -3.14mmHg; 95% CI: -4.44 - -1.84; P < 0.00001). Quercetin supplementation decreases BP in normotensive and (pre)hypertensive patients.

In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients (p = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., β-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-β-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.

Viral infections of the lower respiratory tract are considered a public health problem. They affect millions of people worldwide, causing thousands of deaths, and are treated with expensive medicines, such as antivirals or palliative measures. In this study, we conducted a systematic review to describe the use of quercetin-type flavonols against lower respiratory tract viruses and discussed the preclinical impact of this approach on different signs and clinical mechanisms of infection. The systematic review was performed in PubMed/MEDLINE, Scopus, Scielo, and Biblioteca Virtual de Saúde (BVS). After the database search, 11 relevant studies were identified as eligible. The analysis of these studies showed evidence of antiviral activity of quercetin-type flavonols with significantly reduced mortality rate (M-H = 0.19, 95% CI: 0.05 to 0.65, p-value = 0.008) of infected animals and a reduction in the average viral load (IV = -1.93, 95% CI: -3.54 to -0.31, p-value = 0.02). Additionally, quercetin and its derivatives reduced the amount of proinflammatory cytokines, chemokines, reactive oxygen species, mucus production, and airway resistance in animals infected with a respiratory virus. Overall, supplementation with quercetin-type flavonols is a promising strategy for treating viral-induced lower respiratory tract infections. © 2021 John Wiley & Sons Ltd.

CONTEXT: Clinical trials examining the cardiovascular protective effects of quercetin in humans have reported conflicting results. OBJECTIVE: The aim of this systematic review was to summarize evidence of the effects of quercetin supplementation on plasma lipid profiles, blood pressure (BP), and glucose levels in humans by performing a meta-analysis of randomized controlled trials. DATA SOURCES: MEDLINE, Embase, and Scopus databases were searched electronically from their inception to July 2018 to identify randomized controlled trials that assessed the impact of quercetin on lipid profiles, BP, and glucose levels. STUDY SELECTION: Randomized controlled trials assessing the effects of quercetin or a standardized quercetin-enriched extract on plasma lipid profiles, BP, and glucose levels in humans were eligible for inclusion. DATA EXTRACTION: A random-effects model was used for data analysis. Continuous variables were expressed as weighted mean differences (WMDs) and 95%CIs. Subgroup analyses were conducted to explore possible influences of study characteristics. Sensitivity analyses were also performed, as were analyses of publication bias. RESULTS: Seventeen trials (n = 896 participants total) were included in the overall analysis. Pooled results showed that quercetin significantly lowered both systolic BP (WMD, -3.09 mmHg; 95%CI, -4.59 to -1.59; P = 0.0001) and diastolic BP (WMD, -2.86 mmHg; 95%CI, -5.09 to -0.63; P = 0.01). Neither lipid profiles nor glucose concentrations changed significantly. In subgroup analyses, significant changes in high-density lipoprotein cholesterol and triglycerides were observed in trials with a parallel design and in which participants consumed quercetin for 8 weeks or more. CONCLUSION: Quercetin intake resulted in significantly decreased BP in humans. Moreover, participants who consumed quercetin for 8 weeks or more showed significantly changed levels of high-density lipoprotein cholesterol and triglycerides in trials with a parallel design. © The Author(s) 2020. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@o

BACKGROUND: The lipid profile is associated with metabolic diseases in overweight and obese individuals. Quercetin treatment is suggested to reduce the risk factors for obesity. OBJECTIVE: The aim of the literature meta-analysis was to determine the range of doses of quercetin administration on plasma lipid levels in overweight and obese human subjects. METHODS: Articles searched on EMBASE, PubMed, Cochrane Library, and Web of Science through March 20, 2019, were reviewed independently using predetermined selection criteria. The Cochrane collaboration's tool for assessing risk of bias was used to assess the quality of the included trials. Heterogeneity was measured using Cochran's Q test and the I-square (I2) statistic. Data were pooled using a random-effects model and the standardized mean difference (SMD) was considered for measuring the overall effect size. RESULTS: Of 176 articles reviewed, 9 randomized clinical trials were selected based on the inclusion criteria. The pooled results for the effect of quercetin administration on LDL-cholesterol (SMD: -002; 95% CI: -0.15-0.11), HDL-cholesterol (SMD: -0.06; 95% CI: -0.19-0.07), triglycerides (SMD: 0.05; 95% CI: -0.08-0.18), and total cholesterol (SMD: 0.04; 95% CI: -0.09-0.17) were not significantly different from the control group results. Quercetin administration at doses of ≥250 mg/day (SMD: -0.58 ; 95% CI: -0.94--0.22) and total dose ≥14,000 mg (SMD: -0.58 ; 95% CI: -0.94--0.22) significantly reduced LDL levels; however, HDL-cholesterol, triglycerides, and total cholesterol levels remained unchanged (p > 0.05). CONCLUSION: Quercetin administration does not affect plasma lipid levels in overweight and obese individuals. However, it significantly reduces LDL-cholesterol levels at doses of ≥250 mg/day and total dose ≥14000 mg.

BACKGROUND/OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 pan

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 wa

BACKGROUND: The Qi-deficiency constitution (QDC) is a body constitution type characterized by weakened immune function and increased susceptibility to infectious diseases. Emerging evidence indicates that Chinese herbal medicine can effectively improve immunological competence in individuals with QDC. This study aims to systematically evaluate the clinical efficacy of the Qi-Xu-Tiao-Ti Formula (QXTTF) in alleviating QDC and elucidate its underlying pharmacological mechanisms through transcriptome sequencing and network pharmacology approaches. METHODS: This single-center randomized controlled trial was performed using QXTTF to treat the QDC subjects, with Balanced constitution (BC) as the healthy controls. Primary outcome measures focused on traditional Chinese medicine constitution assessment of QDC scores, with secondary evaluation parameters including immune biomarkers (IgA and IgG levels) and adverse events monitoring. To investigate the molecular mechanisms, we performed transcriptomic profiling to identify QXTTF-responsive gene targets, followed by integrated network pharmacology analysis, molecular docking simulations to characterize the compound-target interactions underlying QXTTF's therapeutic effects, and ultimately validated at the proteomics level. RESULTS: This study recruited 78 participants, comprising 63 QDC and 15 BC individuals. Comparative analysis between QDC and BC groups revealed significant differences in immunoglobulin IgA, IgG levels, and transcriptomic profiles. QXTTF intervention on QDC subjects significantly reduced the QDC scores (p < 0.05) and enhanced IgA and IgG production (p < 0.01), indicating QXTTF's dual efficacy in constitution regulation and potential immunomodulation. Transcriptome sequencing identified eight putative therapeutic targets: ATP2A1, GOT1, SLC16A8, FTCD, ERBB2, GSS, VLDLR, and IL2. Functional enrichment analysis revealed significant overrepresentation of differentially expressed genes in immune-related pathways, notably "natural killer cell-mediated cytotoxicity", "T cell receptor signaling pathway", and "B cell receptor signaling pathway". Molecular docking simulations confirmed stable binding conformations b

The Carob tree is an evergreen tree of the Mediterranean. Carob pods are highly nutritious. Despite their high sugar content, carob pods contain insoluble fibers, D-pinitol as well as phenolic compounds. The purpose of this study was to compare acute postprandial glycemic and insulinemic responses to beverages containing Imera carob powder versus sucrose in healthy male adults and to characterize the phenolic profile of the Imera variety using LC-TTOF MS. A randomized, controlled crossover study examined the glycemic effects of beverages made with Imera carob powder (30 g) versus sucrose (14 g) in 15 healthy males. After an overnight fast and 1-month washout between sessions, participants consumed both beverages. Carob significantly lowered glucose levels (109.2 vs 120.3 mg/dL, p = 0.003) and insulin levels (9.8 vs 14.6 μIU/mL, p = 0.001) at 30 min, with reduced AUCi values for both glucose and insulin at 0-30 and 30-60 min. LC-TTOF MS analysis revealed that the Imera cultivar contains phenolic compounds, including gallic acid, catechin, quercetin, myricetin and kaempferol.

The purpose of this study was to investigate whether quercetin ingestion increases the decline in muscle contractile capacity due to a single resistance exercise session at differing intensities. Thirty-eight older adults took part in this study. They were divided into three intensity groups: low- (LI), moderate- (MI), and high-intensity (HI) groups. Each participant completed two single resistance exercise sessions of resistance exercise at 40 (LI), 60 (MI), or 80 (HI) percent of maximal voluntary contraction. Before each session, they ingested either a placebo or quercetin glycoside (500 mg). Motor unit behavior and electrically elicited contraction torque were measured by high-density electromyography and neuromuscular electrical stimulation at pre-ingestion, post-ingestion, and post-exercise. Quercetin ingestion decreased the motor unit recruitment thresholds from pre- to post-ingestion (p < 0.001). The decline in electrically elicited contraction torque following exercise was greater with quercetin than placebo ingestion in LI and MI groups (low: p = 0.014; moderate: p = 0.025), but not in the HI group (p = 0.792). The greater the decline of electrically elicited contraction torque following exercise by quercetin ingestion, the greater the decrease in the recruitment threshold of motor units with a higher threshold by quercetin ingestion in LI and MI groups (low: p = 0.047, rs = 0.566; moderate: p = 0.011, rs = 0.692), but not in the HI group (p = 0.228). These results suggest that quercetin ingestion accelerates the decline in muscle contractile capacity following low- or moderate-intensity resistance exercise, possibly due to the additional recruitment of higher-threshold motor units.

Erratum in J Food Sci. 2026 Jun;91(6):e71198. doi: 10.1111/1750-3841.71198. Quercetin-3-O-rutinoside (Q3R) is a bioflavonoid characterized by the attachment of rutinose, an indigestible disaccharide, to quercetin. EubioQuercetin is a standardized Q3R formulation with improved water solubility. This study aimed to clarify the similarities and differences between EubioQuercetin, Q3R, and conventional quercetin by comparing their microbiological and pharmacokinetic properties. Fecal microbiota analyses showed that the addition of EubioQuercetin significantly increased Blautia and [Ruminococcus] gnavus groups (p < 0.05) and significantly decreased Faecalibacterium and deoxycholic acid (p < 0.05). Correlation analysis of intestinal bacteria showed a significant positive correlation between the relative abundance of Fusicatenibacter and Christensenellaceae R-7 group before the addition of EubioQuercetin and its fold change before and after the addition of EubioQuercetin. In a randomized, open-label, two-sequence/two-period crossover clinical trial, the eight major blood metabolites and their blood abundance ratios showed almost the same tendency between EubioQuercetin and quercetin, with or without rutinose. The pK profile of EubioQuercetin showed a 5-fold increase in Cmax and a 4-5-fold increase in AUClast compared with those of quercetin; the Tmax was 2-3 times longer; the t1/2 was more than 2-fold longer after 4 weeks of continuous administration. A similar trend to that observed in the in vitro human fecal microbiota assay was seen, with increased fluctuations in intestinal bacterial composition following 4 weeks of EubioQuercetin consumption. Preliminary findings indicate that the increased water solubility of EubioQuercetin promotes catabolic and metabolic reactions in intestinal bacteria, and that the tendency of intestinal bacteria to fluctuate is different from that of conventional quercetin. © 2025 Institute of Food Technologists.

BACKGROUND/OBJECTIVES: Vitamin C is frequently used in several dietary supplements due to its proposed health-promoting properties, while phenolic compounds and especially flavonoids have been suggested to provide synergistic antioxidant and cardiovascular benefits. However, the specific interactions between these compounds and their individual contributions to biological activity remain underexplored. This study aimed to evaluate the antioxidant potential and anti-inflammatory and antiplatelet biological effects of a high-dose (1 g) vitamin C-low-dose (50 mg) bioflavonoid (VCF)-based supplement using both in vitro and in vivo approaches in human platelets. METHODS: Total phenolic content was quantified and antioxidant capacity was assessed using DPPH, FRAP, and ABTS assays and compared to individual phenolic standard compounds, including (simple phenolics like gallic acid, flavonoids like quercetin and catechin, and polyphenols like curcumin and tannin), and a standard supplement containing only high-dose vitamin C (VC). ATR-FTIR spectroscopy was used to assess molecular interactions between vitamin C and flavonoids. In vitro anti-inflammatory and antiplatelet activities of all supplements and standards were assessed by quantifying their IC50 values against ADP, PAF, and thrombin-induced platelet aggregation. The in vivo evaluation of the efficacy and synergy of VCF supplement versus VC was achieved by a two-arm clinical study in healthy volunteers by quantifying their platelet reactivity, which was measured via EC50 values on the aforementioned platelet agonists (PAF, ADP, and Thrombin) before (t = 0) and after receiving either solely VC or VCF supplementation for four weeks. RESULTS: From all phenolic standards, the flavonoids and especially a mixture of flavonoids (catechin + quercetin) showed higher in vitro antioxidant capacity and anti-inflammatory and antiplatelet efficacy, followed by polyphenols and then simple phenolics. The VCF supplement showed the most potent antioxidant capacity, but also the strongest anti-inflammatory and antiplatelet activities too, in comparison to the VC and the mixture of flavonoids, suggesting higher synergy and thus bio-ef

PURPOSE: Post-cesarean section pain management remains a crucial challenge in obstetric care, with implications for maternal recovery, mother-child bonding, and long-term health outcomes. Quercetin, a naturally occurring flavonoid with anti-inflammatory and antioxidant properties, has shown promising analgesic effects in preclinical studies but has limited clinical evidence for acute pain management. This study aimed to assess the efficacy of preoperative Quercetin administration on acute post-operative pain following cesarean section. PATIENTS AND METHODS: In this prospective, double-blinded, randomized controlled trial, 80 patients undergoing elective cesarean section under spinal anaesthesia were randomly allocated to receive either 500 mg oral Quercetin (n=40) or matching placebo (n=40) one hour before surgery. The primary outcome was postoperative pain intensity assessed using a 10 cm Visual Analog Scale (VAS) at 2, 6, 12, and 24 hours after surgery. Secondary outcomes included time to first analgesic request, total morphine consumption, incidence of postoperative nausea and vomiting, time to physical activity initiation, functional activity, patient satisfaction, and adverse effects. RESULTS: The Quercetin group demonstrated significantly lower VAS scores at all measured time points (p<0.001) and delayed time to first analgesic request (3.9±1.3 vs 2.73±0.78 hours, p<0.001) compared to the placebo group. Additionally, patients receiving Quercetin initiated physical activity significantly earlier (15.2±1.9 vs 19.03±2.66 hours, p<0.001) and reported higher satisfaction levels on postoperative day 2 (p=0.042). However, total morphine consumption, functional activity, incidence of nausea and vomiting, and hospital length of stay were comparable between groups, with no significant differences in adverse effects. CONCLUSION: Preoperative administration of 500 mg Quercetin significantly reduced postoperative pain and delayed the need for rescue analgesia following cesarean section, allowing for earlier mobilization without increasing adverse effects. These findings suggest Quercetin may serve as a safe, effective adjunct in multimodal pain management protocols for

ZXGD Decoction, a traditional Chinese formulation historically used for cardiovascular ailments, was evaluated for its efficacy in coronary heart disease (CHD) through an integrated network pharmacology and randomized controlled trial (RCT) approach. Its selection was rooted in documented therapeutic benefits for blood stasis and endothelial dysfunction, with modern pharmacology identifying active compounds (e.g., luteolin, quercetin) targeting inflammation and oxidative stress pathways. Network analysis revealed ZXGD’s multi-target mechanism, prominently modulating the PI3K-AKT and NF-κB pathways, supported by robust molecular docking scores (binding affinity < -7.0 kcal/mol). These findings align with CHD pathophysiology, suggesting ZXGD disrupts critical inflammatory cascades. In a double-blind RCT (n = 180), ZXGD adjunct therapy significantly improved angina frequency (35% reduction vs. control, p < 0.01) and endothelial function (FMD increase: 2.8% ± 0.5 vs. 1.2% ± 0.4, p < 0.05) over 12 weeks, with no severe adverse events. This underscores ZXGD’s clinical potential as a safe complementary treatment. Notably, lipid profile enhancements (LDL-C reduction: 18.3% vs. 11.7%) correlated with predicted network targets, including LDLR and HMGCR. Our results bridge traditional use with mechanistic evidence, reinforcing ZXGD’s role in CHD management. While prior studies emphasize ZXGD’s anti-thrombotic effects, this work uniquely validates its anti-inflammatory and lipid-modulating properties, addressing gaps in understanding its systemic impact. Clinically, these findings advocate for ZXGD’s integration into CHD therapeutic protocols, particularly for patients with residual inflammatory risk. © 2025. The Author(s).

Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double-blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre-surgery through hospital discharge. Primary outcomes were reduced inflammation and improved endothelial function ex vivo. Exploratory analyses included plasma proteomics and single-nuclei RNA sequencing of internal thoracic artery (ITA) samples. Quercetin treatment showed a trend toward reduced C-reactive protein at discharge (p = 0.073) and differentially modulated circulating inflammatory protein expression between men and women, with a pro-inflammatory effect of quercetin in females. Endothelial acetylcholine-induced relaxation improved significantly with quercetin (p = 0.049), with effects in men (p = 0.043) but not in women (p = 0.852). ITA transcriptomics revealed the overexpression of senescence and inflammaging pathways in male vascular cells, which quercetin reversed. In female cells, quercetin had minimal endothelial benefit and increased inflammaging in fibroblasts. In male cells, a candidate target of quercetin involves interactions between the receptor PLAUR and its ligands PLAU and SERPINE1. Post-operative atrial fibrillation incidence was significantly lower with quercetin, representing 4% of the patients compared to 18% in the placebo group (p = 0.033). In conclusion, short-term quercetin treatment effectively targeted vascular senescence in male CAD patients, improving inflammatory and functional outcomes. However, these benefits were not observed in female patients. Trial Registration: https://clinicaltrials.gov, NCT04907253. © 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Quercetin, a naturally occurring flavonoid, exhibits antiproliferative and pro-apoptotic effects across various cancer models. Topotecan, a topoisomerase I inhibitor, is used in the treatment of retinoblastoma; however, its clinical utility is limited by dose-dependent toxicity. This study aimed to investigate whether quercetin is associated with enhanced topotecan-induced cytotoxicity in retinoblastoma and to explore the underlying mechanisms under both two-dimensional (2D) and three-dimensional (3D) conditions. Cell viability was assessed using the MTT assay, and drug interactions were evaluated using the combination index (CI) based on the Chou-Talalay method. Apoptosis was analyzed by Annexin V-FITC/PI staining and flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential were evaluated using fluorometric methods, and N-acetyl-L-cysteine (NAC) was used for functional modulation of oxidative stress. Three-dimensional tumor spheroid models were used to assess treatment effects under conditions that partially recapitulate tumor architecture. Gene expression levels of apoptosis-related markers and PI3K/Akt/mTOR pathway components were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The combination of quercetin and topotecan was associated with synergistic cytotoxic effects in Y79 cells (CI < 1), accompanied by increased ROS levels, mitochondrial membrane depolarization, and elevated apoptotic cell death. NAC co-treatment partially attenuated ROS levels and restored cell viability. In 3D spheroid models, combination treatment induced structural disruption, reduced viability, and increased cell death, effects that were partially reversed by NAC. Gene expression analysis revealed upregulation of pro-apoptotic genes and downregulation of survival-related genes, along with increased PTEN expression. Quercetin is associated with enhanced topotecan-induced cytotoxicity in retinoblastoma cells under both 2D and 3D conditions. These effects were associated with ROS-associated cellular stress, mitochondrial dysfunction, and modulation of apoptotic and survival-related pathways. The partial rescue by NAC supports a co

BACKGROUND: Molecular targeted therapies play a crucial role in the management of hepatocellular carcinoma (HCC). Lenvatinib is a standard targeted agent for advanced HCC, while quercetin has emerged as a promising natural compound with anti-HCC potential. This study investigates the combined effect of quercetin and lenvatinib on HCC. METHODS: The human HCC cell line Huh7 and a nude mouse subcutaneous xenograft model were utilized. We evaluated cell proliferation, clonogenicity, invasion, migration, and apoptosis through Cell Counting Kit-8 (CCK-8), clonogenic, Transwell, and flow cytometry assays, respectively. Network pharmacology analysis was performed identify common targets. The protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X-protein (Bax), E-cadherin, N-cadherin, and protein tyrosine kinase 2 (PTK2) were assessed by Western blotting. In vivo experiments were conducted to validate the anti-tumor efficacy of the combination treatment. RESULTS: The combination of quercetin and lenvatinib significantly enhanced inhibition of Huh7 cell proliferation, colony formation, invasion, and migration (p < 0.01) and promoted apoptosis (p < 0.01) compared to individual treatments. Mechanistically, the combination treatment decreased the expression of Bcl-2 and N-cadherin while upregulating Bax and E-cadherin. PTK2 was identified as a key shared target, and the combination most effectively suppressed its protein expression. In vivo, the combination group demonstrated a higher tumor inhibition rate (p < 0.01) and a Combination Index (CDI) of 0.753. CONCLUSION: Quercetin significantly enhances the anti-tumor efficacy of lenvatinib, likely through synergistic inhibition of PTK2 expression. © 2026 The Author(s). Published by IMR Press.

Ferroptosis, a newly identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a promising therapeutic strategy for triple-negative breast cancer (TNBC) due to the heightened susceptibility of TNBC cells to this form of cell death. Nonetheless, the unique hypoxic and acidic tumor microenvironment confers resistance to ferroptosis, which limits the clinical efficacy of single-agent ferroptosis inducers. To overcome this, we developed a synergistically enhancing ferroptosis nanomedicine named sorafenib (SOR)-quercetin (QUE) nanoparticles (SQ NPs) by co-assembling SOR, QUE, and polyvinylpyrrolidone K30 (PVP K30). In this system, SOR facilitates ferroptosis by downregulating the expression of glutathione peroxidase 4 (GPX4). Simultaneously, QUE mitigates the hypoxic tumor microenvironment by suppressing the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and hexokinase Ⅱ (HK-Ⅱ), thereby inhibiting glycolysis, reducing LA production, and impeding GSH synthesis. This multifaceted approach culminates in enhanced ferroptosis in TNBC cells. In vivo studies on antitumor and antimetastatic effects have demonstrated the superior therapeutic efficacy and metastasis-inhibiting capabilities of SQ NPs in the context of TNBC. This report highlights the therapeutic potential of QUE in synergy with SOR under hypoxic conditions, offering a novel strategic approach for the treatment of TNBC.

Hedyotis diffusa Willd (HD) and Scutellaria barbata D.Don (SB) are widely used traditional Chinese herbs with detoxifying properties and anti-tumor activities. The HD-SB pairing demonstrated significant anti-tumor efficacy in cancer, however, the synergistic potential of HD-SB with cisplatin in the treatment of cancer remains poorly understood. The current work aimed to uncover the synergistic effect of HD-SB with cisplatin on ovarian cancer. In the present study, the combination of HD-SB and cisplatin exhibited a pronounced inhibitory effect on the proliferation, migration and invasion, while promoting effect on apoptosis of ovarian cancer cells. Moreover, the interaction between drug compounds and disease targets contained 277 nodes and 1395 edges, the highlighting active ingredients were quercetin, luteolin, wogonin. Among the PPI network, the top targets were TP53, STAT3, SRC, AKT1, HSP90AA1, ESR1, EGFR, TNF, PIK3R1, IL6, PIK3CA, PIK3CB. Furthermore, GO enrichemnt analysis revealed that the target intersection mainly involved in biological process, cellular component and molecular function, KEGG analysis revealed that the target intersection mainly contained the pathways in cancer, PI3K/AKT signaling pathway, proteoglycans in cancer, MAPK signaling pathway. Ultimately, the molecular docking revealed that quercetin, luteolin and wogonin exhibited significant affinity with AKT1 and PIK3CA. Mechanistically, HD-SB enhance the anti-tumor effect of cisplatin on ovarian cancer via PI3K/AKT pathway. Taken together, our study revealed that the combination of HD-SB exhibited an enhanced capacity to improve cisplatin sensitivity in ovarian cancer cells through the PI3K/AKT pathway. HD-SB in combination with cisplatin could be a potential therapeutic strategy for the treatment of ovarian cancer patients. © 2026. The Author(s).

Pulmonary fibrosis (PF) is a progressive condition characterized by inflammation and excessive fibrous tissue formation. Pirfenidone, an FDA-approved drug, slows PF progression through reducing TGF-β production and antioxidant effects. Quercetin (Quer) has emerged as a promising candidate for PF management, exhibiting anti-inflammatory and antioxidant effects and inhibiting collagen synthesis in various tissues. Our study was designed to explore the therapeutic potential of combining Pirf and Quer in mitigating bleomycin-induced lung fibrosis in vivo. Using a bleomycin (BLM)-induced lung fibrosis model, the study evaluated the anti-fibrotic effects of Pirf and Quer, both individually and together. Oxidative stress biomarkers (MDA, SOD, GSH-Px), inflammatory cytokines (TNF-α, IL-1β), and gene expression of NF-κB, PPAR-γ, PI3K, TLR-4, and MAPK were measured to assess the cellular response. BLM exposure markedly upregulated inflammatory markers and oxidative stress, with reducing antioxidant defense mechanisms. Treatment with Pirf moderately decreased these fibrotic changes. Quer, known for its potent antioxidant properties, exhibited a stronger reduction in these parameters. BLM treatment increased the expression of NF-κB, PI3K, TLR-4, and MAPK while Pirf and Quer were shown to reduce them significantly. However, PPAR-γ mRNA levels were reduced by BLM treatment and increased by both Pirf and Quer. Notably, the concomitant administration of Pirf and Quer always provided an augmented effect. The combined administration of Pirf and Quer significantly alleviated BLM-induced lung fibrosis more effectively than either drug alone, suggesting that this combination therapy could enhance anti-fibrotic treatments and should be further investigated in clinical settings. © 2026 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.

Natural polyphenols, particularly quercetin (QUE) and rosmarinic Acid (RA), possess significant synergistic therapeutic potential as potent antioxidants and anti-inflammatories. However, their poor stability, low water solubility, and resulting limited bioavailability severely hinder their effective clinical translation. This study addresses these fundamental limitations by designing a novel advanced drug delivery platform utilizing electrospinning. We have fabricated composite high-molecular-weight poly(L-Lactic Acid) (PLA)/polyethylene glycol (PEG) nanofibers for the simultaneous co-delivery of both QUE and RA, optimizing compound stability and release kinetics. PLA provided mechanical integrity and sustained release properties, while the incorporation of PEG strategically enhanced the mat's wettability, enabling precise control over initial drug dissolution. Comprehensive characterization confirmed uniform, bead-free morphology and high entrapment efficiency for both polyphenols. Crucially, the PLA/PEG blend successfully achieved a biphasic release profile, featuring an initial burst release mediated by PEG followed by a sustained release phase governed by the PLA matrix. Furthermore, the performed in vitro investigations using SH-4 melanoma cells and HaCaT normal keratinocytes revealed that the prepared novel materials containing the polyphenols possessed high anticancer activity to the used cancer cell line. However, the toxicity to the normal cell line is much lower. Therefore, this novel electrospun composite scaffold offers an effective strategy to enhance the stability, control the delivery, and maximize the synergistic therapeutic benefits of quercetin and rosmarinic Acid for applications in areas such as advanced wound care, tissue regeneration, and antitumor therapies.

The natural flavonoids quercetin (Que) and kaempferol (Kae) show great potential for anti-aging applications but suffer from poor solubility and skin permeability. This study aimed to develop a synergistic topical emulsion system to overcome the poor bioavailability of the Que and Kae for enhanced efficacy. The optimal synergistic molar ratio (Que:Kae = 1:2) was first identified via 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and cellular assays. The drugs were then loaded into milk-derived exosomes (mExo) using a Box-Behnken design (BBD), achieving high encapsulation (>69%), a size of ∼120 nm, and a polydispersity index (PDI) of 0.180. This complex was incorporated into an oil-in-water emulsion, with its formulation also BBD-optimized for stability. In a D-galactose-induced skin aging mouse model, the final Que/Kae-mExo@Eml formulation significantly outperformed control groups (free drug mixture, blank exosome emulsion, and vitamin C). It most effectively reduced oxidative stress (malondialdehyde, MDA), enhanced antioxidant enzymes (superoxide dismutase, SOD and glutathione, GSH), suppressed matrix metalloproteinase-1 (MMP-1), promoted collagen I (Col I) synthesis, and improved skin histology, elasticity, and hydration. In conclusion, an optimized, stable emulsion leveraging a synergistic 1:2 drug ratio and an mExo delivery system was successfully developed, demonstrating superior comprehensive efficacy against skin aging.

Hydroxypropyl-β-cyclodextrin (HPβCD) serves as an effective carrier for enhancing the delivery of poorly soluble actives. In this work, an HPβCD-based delivery system encapsulating the marine carotenoid fucoxanthin (FUCO) and the transporter-regulating isoquercitrin (IQ) was prepared via high-pressure homogenization (HPH). The Caco-2 monolayer model demonstrated that IQ significantly enhanced FUCO transport across the intestinal barrier. This effect arose from IQ's synergistic action: promoting scavenger receptor class B type 1 (SR-B1)-dependent endocytic uptake while inhibiting ATP-binding cassette transporter B1 (ABCB1)-mediated efflux. At the optimal IQ/FUCO molar ratio (1: 2), SR-B1 expression increased 1.3-fold, ABCB1 expression decreased by 70.7%, and FUCO transmembrane transport rose 14.5-fold. Under the optimized conditions, HPβCD achieved an 88.7% encapsulation efficiency of FUCO. Fourier transform infrared spectroscopy (FTIR), electron microscopy observations, and X-ray diffraction (XRD) confirmed the encapsulation of FUCO and IQ within HPβCD's hydrophobic cavity. In vivo studies demonstrated that HPβCD-based delivery of IQ dramatically enhanced FUCO's oral bioavailability, elevating hepatic exposure of FUCO and its metabolites by 3.28-fold. Simultaneously, a 1.5-fold increase in intestinal SR-B1 expression and a 20% inhibition of ABCB1 expression were also observed. This work validates a "carrier encapsulation-transporter modulation" dual strategy, combining HPβCD encapsulation with IQ-mediated regulation of key transporters (SR-B1/ABCB1), providing a novel approach for the efficient development of marine-derived nutraceuticals.

ETHNOPHARMACOLOGICAL RELEVANCE: The Danshen (root of Salvia miltiorrhiza Bge.) and Shanzha (fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (SD) herb combination is a commonly used traditional Chinese medicine with potential for treating cardiovascular diseases. This study aimed to evaluate the anti-MASLD efficacy of SD and the potential mechanism of synergistic treatment of MASLD with its active ingredients. MATERIALS AND METHODS: The chemical composition of SD was elucidated using high-resolution mass spectrometry. A mouse model of MASLD was developed to assess therapeutic efficacy of SD. An integrated method, combining network pharmacology and multi-omics, was utilized to explore the anti-MASLD effects and mechanisms of SD. Additionally, molecular docking, Western blotting (WB), and other methodologies were employed to investigate the synergistic intervention mechanisms of SD's active ingredients in MASLD. RESULTS: SD can substantially mitigate liver lipid accumulation and inflammation in MASLD mice. We identified 92 components in SD, of which 55 were recognized as potential active ingredients. Notably, four chemical constituents-rutin, quercetin, salvianolic acid B, and hyperoside-have been identified as the active compounds responsible for the anti-MASLD effects of SD. Rutin, hyperoside and salvianolic acid B interacts with the Plin-5, facilitating the recruitment of lipid droplets to the mitochondria. Subsequently, salvianolic acid B, rutin and hyperoside activates PPARα, thereby promoting the oxidation of fatty acids. Concurrently, rutin, hyperoside and quercetin modulates Plin-2 to mitigate excessive fatty acid oxidation, thereby reducing the risk of oxidative stress. CONCLUSIONS: Our research preliminarily confirms the anti-MASLD effects and the mechanism of synergistic intervention by SD's active ingredients, providing valuable evidence to support the use of TCM formulae for treating MASLD.

Oral nitrite supplementation enhances nitric oxide (NO) bioavailability and lowers blood pressure. Quercetin may facilitate the reduction of nitrite to NO. However, the combined effects of nitrite and Quercetin on gastric NO formation and blood pressure have not been explored. We investigated whether oral treatment with Quercetin enhances the gastric conversion of nitrite to NO (in vitro and in vivo) and exerts antioxidant and antihypertensive effects. Spontaneously hypertensive rats (SHR) were divided into six groups (n = 6/group): three groups treated with Quercetin 10 mg/kg followed 15 min later by water, nitrite 1 mg/kg (nonantihypertensive) or 15 mg/kg (antihypertensive) by gavage, and three similar control groups treated with vehicle, followed by the same nitrite treatments. Blood pressure, gastric NO, plasma nitrite, nitrate, nitrosylated species (RxNO) and aortic S-nitrosylated proteins were measured. Oxidative stress was also assessed. Quercetin treatment converted a nonantihypertensive dose of nitrite into an effective antihypertensive intervention in association with increased in vitro and in vivo gastric NO formation. However, Quercetin did not enhance nitrite-induced increases in systemic or vascular nitrite, nitrate, RxNO concentrations nor vascular protein nitrosation. Our results show that Quercetin is a potent enhancer of gastric NO formation from nitrite and amplifies its antihypertensive effects. This combination of drugs may represent a safe and effective therapeutic strategy. Plain Language Summary: Nitric oxide (NO) is important to control blood pressure. Sodium nitrite can increase NO levels, and quercetin, a common dietary antioxidant, may enhance this effect. In this study, hypertensive rats received nitrite with or without quercetin. Quercetin boosted the stomach’s ability to convert nitrite into NO, turning a low, otherwise ineffective nitrite dose into one that lowered blood pressure. This effect was linked to increased NO formation in the stomach, but not in the blood or vessels. Taken together, quercetin and nitrite may safely improve blood pressure control. © 2026 The Author(s). Basic & Clinical Pharmacology & Toxicology publishe