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The low bioavailability of most phytochemicals limits their anticancer effects in humans. The present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed of Arctium lappa, with green tea (GT) and quercetin (Q) enhances the chemopreventive effect on prostate cancer. We performed in vitro proliferation studies on different cell lines. We observed a strong synergistic anti-proliferative effect of GT+Q+Arc in exposing androgen-sensitive human prostate cancer LNCaP cells. The pre-malignant WPE1-NA22 cell line was more sensitive to this combination. No cytotoxicity was observed in normal prostate epithelial PrEC cells. For an in vivo study, 3-week-old, prostate-specific PTEN (phosphatase and tensin homolog) knockout mice were treated with GT+Q, Arc, GT+Q+Arc, or the control daily until 16 weeks of age. In vivo imaging using prostate-specific membrane antigen (PSMA) probes demonstrated that the prostate tumorigenesis was significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), and 90% (GT+Q+Arc) compared to the control. A pathological examination showed that all control mice developed invasive prostate adenocarcinoma. In contrast, the primary lesion in the GT+Q and Arc alone groups was high-grade prostatic intraepithelial neoplasia (PIN), with low-grade PIN in the GT+Q+Arc group. The combined effect of GT+Q+Arc was associated with an increased inhibition of the androgen receptor, the PI3K/Akt pathway, Ki67 expression, and angiogenesis. This study demonstrates that combining Arc with GT and Q was highly effective in prostate cancer chemoprevention. These results warrant clinical trials to confirm the efficacy of this combination in humans.

Quercetin (Qc) possesses anti-cancer properties, such as cell signaling, growth suppression, pro-apoptotic, anti-proliferative, and antioxidant effects. In this study, we developed an alginate-modified ZIF-8 (Alg@ZIF-8) to enhance the anti-tumor efficacy of Qc. The developed alginate-modified quercetin-loaded ZIF-8 (Alg@Qc@ZIF-8) was characterized using scanning electron microscope (SEM), dynamic light scattering (DLS), fourier transform infrared spectroscopy Thermogravimetric analysis, Brunauer–Emmett–Teller, and x-ray diffraction. The drug release pattern was evaluated at pH 5.4 and 7.4. The cytotoxicity of nanoparticles was assessed on the 4T1 cell line. Finally, the anti-tumor activity of Alg@Qc@ZIF-8 was evaluated in 4T1 tumor-bearing mice. SEM showed that the nanoparticles were spherical with a diameter of mainly below 50 nm. The DLS showed that the developed nanoparticles' hydrodynamic diameter, zeta potential, and polydispersity index were 154.9 ± 7.25 nm, −23.8 ± 5.33 mV, and 0.381 ± 0.09, respectively. The drug loading capacity was 10.40 ± 0.02%. Alg@Qc@ZIF-8 exhibited pH sensitivity, releasing more Qc at pH 5.4 (about 3.62 times) than at pH 7.4 after 24 h. Furthermore, the IC50 value of Alg@Qc@ZIF-8 on the 4T1 cell line was 2.16 times lower than net Qc. Importantly, in tumor-bearing mice, Alg@Qc@ZIF-8 demonstrated enhanced inhibitory effects on tumor growth and lung metastasis compared to net Qc. Considering the in vitro and in vivo outcomes, Alg@Qc@ZIF-8 might hold great potential for effective breast cancer management. [ABSTRACT FROM AUTHOR]

Background: This study employed a bidirectional Mendelian Randomization (MR) approach to explore the causal relationships between Oral Lichen Planus (OLP), diabetes mellitus (DM), and glycemic control. It also aims to identify potential pharmacological and herbal treatments that effectively address both OLP and the metabolic dysfunctions associated with DM. Methods: This study employs a two-way MR approach to investigate the potential causal relationships between diabetes type and glycated hemoglobin (HbA1c) levels, and the risk of OLP. We analyzed differentially expressed genes from the OLP dataset in the Genomics Expression Omnibus (GEO) database, cross-referencing these with HbA1c-related genes for enrichment analysis. Additionally, the Drug-Gene Interaction Database (DGIdb) and Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to assess the effectiveness of specific drugs, herbs, and ingredients in treating OLP while managing blood glucose levels. Results: The MR analysis revealed a significant association between Type 1 Diabetes mellitus (T1DM) and an increased risk of OLP, unlike Type 2 Diabetes mellitus (T2DM). This finding indicates a unique immunological interaction in T1DM that may predispose individuals to OLP. The drug prediction analysis focused on core targets linked to OLP and HbA1c, evaluating the therapeutic potential of retinoic acid, prednisone, and thalidomide for treating OLP and regulating blood glucose levels. Additionally, herbal medicines such as Ecliptae herbaand Amygdalus communis vas, along with herbal ingredients like quercetin, luteolin, and 17-beta-estradiol, were identified for their anti-inflammatory properties and potential to mitigate metabolic dysfunction in diabetes. Conclusion: The study highlighted a complex interplay between diabetes and OLP, underscoring the efficacy of integrated therapeutic strategies that target both conditions. The findings suggest that both pharmaceutical and herbal treatments can effectively manage the clinical manifestations of OLP and associated metabolic challenges. This holistic approach to treatment could significantly enhance patient outcomes by addressing the interconnected aspects of these chronic conditions. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionsThis study investigates the effects of quercetin, an antioxidant and nitric oxide (NO) modulator, on depressive-like behaviours triggered by social isolation stress (SIS) in mice. SIS, known to harm psychosocial functioning and increase the risk of depression, involves oxidative stress and NO in its pathophysiology.72 male mice were divided into nine groups, including the social (SC) group as the control group (stress-free with normal saline intake). The isolation (IC) groups received normal saline, quercetin at doses of 10, 20, and 40 mg/kg, the nitric oxide synthetase inhibitor L-NAME at a dose of 5 mg/kg, the NO precursor L-arginine at a dose of 100 mg/kg, an ineffective dose of quercetin combined with L-NAME and an effective dose of quercetin combined with L-arginine. Behavioural tests (open-field, forced swimming, and splash tests) were conducted, followed by measuring hippocampal nitrite levels.Quercetin significantly reduced immobility in the forced swimming test, increased activity in the open-field test, and enhanced grooming behaviour, particularly at 40 mg/kg. Co-administration of an ineffective dose of quercetin (10 mg/kg) with L-NAME increased immobility and grooming activity time. Interestingly, co-administration of the effective dose of quercetin (40 mg/kg) with L-arginine increased immobility time in the FST. Additionally, administration of quercetin at doses of 20 and 40 mg/kg significantly reduced the nitrite level in the hippocampus of SIS mice. Furthermore, co-administration of L-NAME and L-arginine with ineffective and effective doses of quercetin decreased and increased nitrite levels in the hippocampus and increased immobility time in the FST compared to their respective counterparts administered alone.These results suggest quercetin’s potential in alleviating depression by modulating NO levels, pointing to its promise in treating depression associated with chronic stressors like social isolation. [ABSTRACT FROM AUTHOR]

Background: One of the most severe consequences of ageing is cognitive decline, which is associated with dysfunction of the brain microvasculature. Thus, repairing the brain vasculature could result in healthier brain function. Methods: To better understand the potential beneficial effect of endothelial progenitor cells (EPCs) in vascular repair, we studied the adhesion and integration of EPCs using the early embryonic mouse aorta–gonad–mesonephros – MAgEC 10.5 endothelial cell line. The EPC interaction with brain microvasculature was monitored ex vivo and in vivo using epifluorescence, laser confocal and two-photon microscopy in healthy young and old animals. The effects of senolysis, EPC activation and ischaemia (two-vessel occlusion model) were analysed in BALB/c and FVB/Ant: TgCAG-yfp_sb #27 mice. Results: MAgEC 10.5 cells rapidly adhered to brain microvasculature and some differentiated into mature endothelial cells (ECs). MAgEC 10.5-derived endothelial cells integrated into microvessels, established tight junctions and co-formed vessel lumens with pre-existing ECs within five days. Adhesion and integration were much weaker in aged mice, but were increased by depleting senescent cells using abt-263 or dasatinib plus quercetin. Furthermore, MAgEC 10.5 cell adhesion to and integration into brain vessels were increased by ischaemia and by pre-activating EPCs with TNFα. Conclusions: Combining progenitor cell therapy with senolytic therapy and the prior activation of EPCs are promising for improving EPC adhesion to and integration into the cerebral vasculature and could help rejuvenate the ageing brain. [ABSTRACT FROM AUTHOR]

One new prenyl flavanone (1), (2S)-8-prenyl-5,6-dihydroxy-7-methoxyflavanone, and one new diarylbutanol (2), (7′S)-3′-hydroxy-linderagatin-A, were isolated from the stem bark of Uvaria siamensis (Annonaceae), along with five known compounds, eriodictyol (3), quercetin (4), paprazine (5), N-trans-caffeoyltyramine (6), and N-trans-feruloyltyramine (7). Their structures were determined through extensive spectroscopic analyses and comparison with the literature. The α-glucosidase inhibitory potential of 1-7 was evaluated. Compound 6 showed the highest inhibitory activity against α-glucosidase and exhibited superior potency compared to the positive control, with an IC50 value of 0.12 μM. [ABSTRACT FROM AUTHOR]

Aim: The study aims to improve glioblastoma multiforme (GBM) treatment by combining temozolomide (TMZ) and quercetin (Qct), using folic acid (FA)-conjugated exosomes to overcome TMZ resistance and enhance blood–brain barrier (BBB) penetration. Methods: Exosomes were isolated and after characterizing and modifying their surfaces with FA, drug loading of TMZ and Qct into exosomes was done. In vitro assays, including cell viability tests, RT-PCR, Western-blotting and flow-cytometry, were performed using U87MG and U251MG GBM cell lines. In vivo analysis included administering exosome-drug formulations to glioblastoma-bearing Wistar rats, monitored through optical imaging and PET scans, followed by post-mortem immunohistochemistry and histological examination. Results: The results showed successful exosome isolation and FA conjugation, with drug release studies indicating accelerated release of TMZ and Qct in acidic conditions, enhancing cytotoxicity. Immunofluorescence indicated greater exosome uptake in GBM cells due to FA conjugation. Cell viability assays demonstrated increased toxicity of the combination therapy, correlating with elevated apoptosis. In vivo studies revealed significant tumor size reduction, alongside increased apoptosis and reduced angiogenesis, particularly in the TMZ-Qct-Exo-FA group. Conclusion: FA-conjugated exosomes loaded with TMZ and Qct represent a promising strategy to enhance GBM treatment efficacy by improving drug delivery, apoptosis induction and inhibiting the PI3K/Akt/mTOR pathway. Graphical Abstract Schematic illustration of exosome isolation and conjugation followed by loading with temozolomide (TMZ) and Quercetin (Qct) for glioblastoma therapy. (A) Process of isolating exosomes and conjugating them with folic acid loaded with TMZ and Qct (B) Function of exosomes conjugated with folic acid in a rat model of glioblastoma (C) Mechanism of how exosomes bearing TMZ and Qct work inside the glioblastoma cell line. Article highlights The study emphasizes the successful use of exosome encapsulation to enhance the delivery of temozolomide (TMZ) and quercetin (Qct) across the blood–brain barrier (BBB), improving drug stability for glioblastoma multiforme (GBM) therapy. Encapsulating TMZ and Qct within exosomes (TMZ-Qct-Exo) showed significantly greater potential in reducing GBM cell viability compared with their unencapsulated counterparts, suggesting an effective approach against TMZ resistance. The introduction of folic acid-conjugated exosomes (TMZ-Qct-Exo-FA) enhanced the targeting of GBM cells, leading to better cellular uptake and improved therapeutic outcomes marked by greater apoptosis and increased caspase-3 levels. The combined treatment effectively inhibited the PI3K/Akt/mTOR signaling pathway, vital for tumor growth and survival, thereby boosting the anti-tumor effects of the TMZ-Qct-Exo-FA treatment. In vivo studies demonstrated that the TMZ-Qct-Exo-FA formulation resulted in superior tumor targeting, significantly reduced tumor size and higher levels of apoptotic markers compared with alternative treatment methods. The findings highlight that exosome-mediated drug delivery could serve as a promising strategy to circumvent resistance mechanisms commonly associated with TMZ in GBM treatment. The research indicates that combining exosome technology with conventional chemotherapy could pave the way for new therapeutic modalities in the treatment of aggressive brain tumors like GBM. The use of folic acid as a targeting moiety suggests an innovative approach to enhance specificity in drug delivery systems directed at tumor cells. These results underscore the need for further clinical studies to explore the full potential of exosome-mediated delivery systems in enhancing the effectiveness of existing cancer therapies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells, but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE: To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments, and to explore the regulatory role of CCR1 and CXCR4. METHODS: Human bone marrow mesenchymal stem cells were selected as experimental subjects. CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells. Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment, respectively. The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology. Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION: (1) 5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells, and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency. (2) To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells, 5 and 10 μmol/L quercetin were selected for the subsequent experiments, and ligustrazine was used as the positive control drug, and the experiments were divided into blank control group, 5 μmol/L quercetin group, 10 μmol/L quercetin group, and 100 μmol/L ligustrazine group. (3) In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment, and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group. (4) The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4. (5) Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA. (6) This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4. [ABSTRACT FROM AUTHOR]

ABSTRACT Dendrobium officinale is a medicinal and food plant with high commercial and medicinal value. Yunnan is known as China's “plant kingdom,” and although the climatic conditions are favorable, the large vertical climatic differences have led to a large difference in the quality of dendrobium from different origins. The analysis of quality differences between several origins with large ecological advantages has not been reported yet. Therefore, the aim of this study is to compare these regions in terms of both morphology and chemical composition and to analyze the variation of their chemical composition in spectral information. The PLS‐DA, SVM, and PLSR models were developed to qualitatively and quantitatively evaluate Dendrobium from different production areas. The results show that the Menghai production area was superior to other production areas in terms of phenotypic morphology, quality, and yield. Within the appropriate range, the higher the specific absorbance, the higher the quercetin content. [ABSTRACT FROM AUTHOR]

Quercetin (QR), recognized as a natural antibacterial ingredient, has found widespread application in the poultry industry. This study investigated the bacteriostatic mechanism and evaluated the in vivo inhibitory impact of caffeic acid-grafted chitosan self-assembled micelles loaded quercetin (CA-g-CS/QR) on avian Escherichia coli (E. coli). The findings indicate that the bactericidal mechanism of CA-g-CS/QR exhibits enhanced efficacy compared to QR alone, disrupting bacterial cell walls, disassembling biofilm structures, and impeding essential components necessary for bacterial growth. Following an avian E. coli attack in broilers, CA-g-CS/QR demonstrated the capacity to enhance the population of beneficial bacteria while concurrently decreasing harmful bacteria within the intestinal tract. Moreover, within 3 days of oral administration of CA-g-CS/QR, a significant decrease in Escherichia spp. count was evident, resulting in the restoration of broilers to a healthy state. CA-g-CS/QR proved to be a significant and more efficacious solution than QR alone for avian E. coli disease. Furthermore, CA-g-CS/QR displayed a broader distribution range and higher concentration within the body. Ten metabolites have been identified in the liver for both QR and CA-g-CS/QR. In conclusion, CA-g-CS/QR has demonstrated a notable capacity to enhance in vitro and in vivo bacterial inhibitory effects, providing foundation for the clinical application of QR in combating avian E. coli infections in broilers. [ABSTRACT FROM AUTHOR]

Specific recognition and detoxification for copper is the key step for the early diagnosis and treatment of various diseases such as neurodegenerative disease and Wilson's disease. Herein, a Chlorella vulgaris‐inspired versatile theranostic nanoparticles is facilely and greenly prepared by assembling quercetin into poly(beta‐cyclodextrin) (PQNPs), which is further employed in the specific recognition and detoxification for Cu2+ in vitro and in vivo. PQNPs can be used in the detection of Cu2+ in aqueous solutions with fast response time (<5 s) and low detection limit (6.499 nM). The detection for Cu2+ in water and serum can be achieved by naked eye instantaneously on a PQNPs‐based paper sensor, and PQNPs can also act as a biological diagnostic agent for the Cu2+ imaging. Remarkably, PQNPs significantly enhance cell viability of the cell models induced by Cu2+ through the synergistic capacities of chelating Cu2+ and antioxidation. The detoxification of PQNPs for copper poisoning model is further ascertained in vivo, and it found that poly‐β‐cyclodextrin is capable of crossing the blood–brain barrier. Taken together, the as‐prepared versatile theranostic nanoparticles possess advantages of simple composition, significant theranostic efficacy, and novel treatment pattern, presenting an intriguing avenue to develop therapeutics for tackling abnormal copper metabolism in the clinic. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii's extensive antibiotic resistance makes its infections difficult to treat, so effective strategies to fight this bacterium are urgently needed. This study aims to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) mediated by Rutin-Gal(III) complex and Quercetin against A. baumannii. Absorbance spectra, fluorescence spectra, and minimum inhibitory concentration (MIC) of Rutin-Gal(III) complex and Quercetin were determined. The intracellular reactive oxygen species (ROS), extracellular polymeric substances (EPS), cell membrane permeability, expression of ompA and blaOXA−23, anti-biofilm activity, and anti-metabolic activity of Rutin-Gal(III) complex- and Quercetin-mediated aPDT were measured. Rutin-Gal(III) complex and Quercetin revealed absorption peaks in the visible spectra. Quercetin and Rutin-Gal(III) complex displayed fluorescence peaks at 524 nm and 540 nm, respectively. MIC values for the Rutin-Gal(III) complex and Quercetin were 64 µg/mL and 256 µg/mL, respectively. Quercetin- and Rutin-Gal(III) complex-mediated aPDT significantly reduced the colony forming units/mL (58.4% and 67.5%), EPS synthesis (47.4% and 56.5%), metabolic activity (30.5% and 36.3%), ompA (5.5- and 10.5-fold), and blaOXA−23 (4.1-fold and 7.8-fold) genes expression (respectively; all P < 0.05). Quercetin- and Rutin-Gal(III) complex-mediated aPDT enhanced notable biofilm degradation (36.2% and 40.6%), ROS production (2.55- and 2.90-folds), and membrane permeability (10.8– and 9.6-folds) (respectively; all P < 0.05). The findings indicate that Rutin-Gal(III) complex- and Quercetin-mediated aPDT exhibits antibacterial properties and could serve as a valuable adjunctive strategy to conventional antibiotic treatments for A. baumannii infections. One limitation of this study is that it was conducted solely on the standard strain; testing on clinical isolates would allow for more reliable interpretation of the results. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSIONS Quercetin is a flavonoid compound with numerous bioactivities. However, the low solubility, easy degradation and low bioaccessibility limit its application. In this study, a novel interfacial crystallized oleogel emulsion was fabricated, where beeswax was used as the oleogelator, for quercetin encapsulation with enhanced stability and bioaccessibility.The process of interfacial crystallization was investigated using interfacial rheology and polarized microscopy, with a positive correlation between crystal density and beeswax content in the oil phase. Emulsion stability was directly linked to beeswax concentration in the oil phase, with 100 mg g−1 showing enhanced stability under storage, UVB light exposure and ionic conditions. Beeswax addition significantly increased the quercetin loading capacity of the emulsion; particularly, at a 200 mg g−1 beeswax concentration, the loading capacity was improved by 285.55%, and the environmental stability was enhanced against UV light and Ca2+. Ultimately, in vitro simulated digestion experiment indicated improved bioaccessibility of quercetin.This strategy significantly enriched the formulation of oleogel emulsion and its potential applications in delivering bioactive ingredients with high environmental vulnerability. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Sodium nitrite is a frequently employed food ingredient; however, extended usage at elevated quantities might result in neurological diseases. Inorganic nitrate is regarded as a source of nitric oxide (NO) and nitrite. Sodium Nitrite is frequently used in several industrial processes including fertilizers and food additives. It can prevent food spoilage and act as antimicrobial agent. Nitrite has a significant impact on controlling intricate physiological and biochemical responses, such as reducing inflammation and preventing blood clotting, which are directly linked to the development and management of cerebrovascular illness. Humans can experience overexposure to nitrite salts through different ways. Excessive amounts of nitrite salts can have harmful effects on human and animal health on different systems including the central nervous system (CNS). Quercetin is a naturally occurring flavonoid with bioactive qualities that has recently garnered significant attention for its protective potential in many diseases. The neuroprotective properties of this substance have been proven by numerous in vitro investigations, as well as in vivo animal experiments and human trials. Multiple researches have documented the potential neuroprotective benefits of quercetin. Conclusions: A recent discovery has revealed the involvement of nitrite in the development of several CNS disorders including the cerebellum indicating its neurotoxicity. However, administration of Quercetin could attenuate these changes due to its neuroprotective effect against the induced oxidative stress and neuronal injury. [ABSTRACT FROM AUTHOR]

Comprehensive comprehension of the interaction between proteins and polyphenols is crucial for advancing their utilization in food processing. This study investigated no‐covalent interaction between pea protein isolate (PPI) and quercetin (Que) through spectroscopic analysis and molecular simulation. Fourier transform infrared spectroscopy and circular dichroism spectrum showed that the interaction between PPI and Que changed the secondary structure of the protein due to a decrease in α‐helix content and an increase in the random coil. Thermodynamic parameters indicated that the Quebound PPI via hydrogen bonds and hydrophobic interactions (ΔH > 0, ΔS > 0, and ΔG < 0), which was also confirmed by molecular docking. Particle size and ζ‐potential showed that PPI and Que demonstrated effective interaction and binding capabilities, enhancing the stability. In addition, the antioxidant and bioaccessibility of complexes have also been enhanced. This study shed a light on the application of protein–polyphenol complexes for developing functional foods. Practical Application: Interaction between pea protein isolate and quercetin can change the protein conformation to maintain the stability of quercetin and is helpful to expand the market value and application value of plant protein. The research has important implications for using leguminous protein as embedded support to improve the stability of polyphenols compounds. [ABSTRACT FROM AUTHOR]

Bladder cancer, which has a rising incidence, is the 10th most common cancer. The transitional cell carcinoma histotype is aggressive and often current therapies are ineffective. We investigated the anti-proliferative effect of quercetin, a natural flavonoid, in combination with the alkylating agent mafosfamide (MFA) on two human bladder cancer cell lines, namely RT112 and J82, representing the progression from low-grade to high-grade tumors, respectively. In both cell types, the combined treatment led to a synergic reduction in cell viability confirmed by a combination index of less than one, though different biological responses were noted. In J82 cells, MFA alone and, to a lesser extent, with quercetin caused cell cycle arrest in the G2/M phase, but only the combined treatment triggered apoptotic cell death. In contrast, in RT112 cells, quercetin induced autophagy, evidenced by the autophagosome formation and the increase in LC-3 lipidation. Interestingly, the synergistic effect was observed only when cells were pre-treated with MFA for 24 h before adding quercetin, not in the reverse order. This suggests that quercetin may help overcome MFA resistance to apoptosis. Although further studies are needed, investigating the combined effects of quercetin and MFA could help elucidate the mechanisms of drug resistance in bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: To assess the cytocompatibility, antibacterial and anti-biofilm efficacy of grape seed extract (GSE) and quercetin hydrogels versus calcium hydroxide (CH) as intracanal medications (ICMs) against an endodontic ex vivo biofilm model. Methods: Single-rooted teeth (n = 50) were prepared and sterilized before being infected with E. faecalis to develop a mature biofilm. They were divided into five equal groups according to the ICM used: G1: medicated with CH paste, G2: medicated with GSE hydrogel, G3: medicated with quercetin hydrogel, G4: positive control group that was infected and not medicated, and G5: negative control group that was neither infected nor medicated. After 1 week, the ICM was removed, and the root canals were cultured to assess the antibacterial efficacy by counting the colony-forming units and the anti-biofilm efficacy by the crystal violet assay. Dead/live bacterial viability was assessed by CFLSM examination, while the cytocompatibility was assessed using the MTT assay. Results: CH had the best antibacterial efficacy, followed by GSE and quercetin hydrogels (p < 0.001). Regarding the anti-biofilm efficacy, GSE was superior, followed by quercetin and CH (p < 0.001). CFLSM examination showed CH and GSE hydrogel to be highly effective in comparison to the positive control (p < 0.0001), with no statistical difference between them (p > 0.05). CH showed significantly higher cell viability percentages using a 500 μg/mL, while quercetin and GSE started to show cell viability > 70% at concentrations of 125 μg/mL and 62.5 μg/mL. Conclusions: CH fulfilled the ideal requirements of ICM as being both antibacterial and non-cytotoxic compared to the other materials tested. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD+) is indispensable for the regulation of biological metabolism. Previous studies have revealed its role in aging and degenerative diseases, while crucially showing that supplementation with NAD+ or its precursors could ameliorate or reverse the progression of aging. Despite extensive evidence for the role and action of NAD+ in aging, its pharmacological activity on the skin, or even its mechanism, has not been elucidated. In this study, we established a novel approach to effectively utilize NAD+ for skin anti-aging by enhancing the pharmacological efficacy of exogenous NAD+ using a phytochemical complex consisting of quercetin, and enoxolone through inhibition of CD38. Through the comprehensive in vitro experiments based on human fibroblasts, we observed that exogenous NAD+ could exert protective effects against both extrinsic aging induced by ultraviolet light exposure and intrinsic aging. Additionally, we found that its effects were significantly boosted by quercetin and enoxolone. In this in-depth study, we demonstrated that these beneficial effects are mediated by improved sirtuin activation, autophagy, and mitochondrial functionality. Our approach is expected to verify the applicability of the topical application of NAD+ and offer more effective solutions for the unmet needs of patients and consumers who demand more effective anti-aging effects. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary artery hypertension (PAH) is a devastating syndrome. Our previous studies showed that perillyl alcohol (P), berberine (B) and quercetin (Q) improve PAH. In this study, we investigated the effects of sub-effective doses of these derivatives in double and triple combination forms on PAH in rats. Materials and Methods: Forty nine rats were divided into seven groups (n=7): 1) control, 2) monocrotaline (MCT), 3) MCT+vehicle (veh), 4) MCT+BP, 5) MCT+PQ, 6) MCT+BQ, and 7) MCT+BPQ. After three weeks of PAH induction with MCT (60 mg/kg), either vehicle (ethanol 5% in saline) or one of the above combinations (dose of 20 mg/kg for B, and doses of 20 and 10 mg/ kg for P and Q in vehicle) was administered for three weeks. Right ventricular (RV) pressure, contractility indices, lung pathology, miR-204 expression, oxidative stress markers, inflammation and apoptosis were assayed. Results: MCT increased RV systolic pressure and hypertrophy, and lung arteriole wall thickness, fibrosis and leukocyte infiltration in the MCT group compared to the CTL group. All treatments improved these effects significantly. Furthermore, MCT reduced antioxidant factors, Bax, P21 and miR-204 expression and increased Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6) and Bcl-2. All of these effects were recovered by combination treatments. Conclusion: The results showed that combination therapy with subeffective/ ineffective doses of these compounds had ameliorative effects against PAH. [ABSTRACT FROM AUTHOR]

Quercetin is a natural flavonoid with antioxidant, anti-inflammatory, and antibacterial properties. This work aimed to formulate quercetin-cyclodextrin microcapsules (QT-β-CD) while examining their photodynamic antibacterial effects and underlying mechanisms in detail. Characterization of the QT-β-CD was conducted using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The bacteriostatic effects of UV-A irradiation on Escherichia coli O157:H7 (E. coli O157:H7) were investigated. The photodynamic impact of QT-β-CD was assessed by analyzing hydrogen peroxide (H₂O₂) production. The antimicrobial activity was further elucidated through examinations of cell membrane integrity, protein damage, changes in cellular motility, biofilm formation, and extracellular polysaccharide reduction. The effect of QT-β-CD on LuxS and motA gene expression in E. coli O157:H7 was investigated by RT-qPCR. The findings demonstrated that QT-β-CD exhibited potent photodynamic properties and functioned as an efficient photosensitizer, causing substantial damage to E. coli O157:H7 cells. These results underscore the potential of quercetin as an antimicrobial agent for food preservation. [ABSTRACT FROM AUTHOR]

Background: When inflammation occurs in periodontal tissues, a dynamic cellular crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal stem cells (BMSCs), which plays a crucial role in the biological behaviour and differentiation of the cells. Recently, flavonoids are increasingly recognized for their therapeutic potential in modulating inflammation and osteogenic differentiation. Owing to their varied molecular structures and mechanisms, there are more needs that flavonoid compounds should be identified by extensive screening. However, current drug research mostly relies on static, single-type cell cultures. In this study, an innovative bionic microfluidic chip system tailored for both soft and hard tissues was developed to screen for flavonoids suitable for treating periodontitis. Methods: This study developed a microfluidic system that bionically simulates the soft and hard structures of periodontal tissues. Live/dead staining, reactive oxygen species (ROS) staining, and RT-qPCR analysis were employed. These techniques evaluated the effects of flavonoid compounds on the levels of inflammatory factors and ROS contents in HGF and HBMSC under LPS stimulation. Additionally, the impact of these compounds on osteogenic induction in HBMSC and the exploration of the underlying mechanisms were assessed. Results: The microfluidic chip used in this study features dual chambers separated by a porous membrane, allowing cellular signal communication via bioactive factors secreted by cells in both layers under perfusion. The inflammatory response within the chip under LPS stimulation was lower compared to individual static cultures of HGF and HBMSC. The selected flavonoids-myricetin, catechin, and quercetin-significantly reduced cellular inflammation, decreased ROS levels, and enhanced osteogenic differentiation of BMSCs. Additionally, fisetin, silybin, and icariside II also demonstrated favorable outcomes in reducing inflammation, lowering ROS levels, and promoting osteogenic differentiation through the Wnt/β-catenin pathway. Conclusions: The bionic microfluidic chip system provides enhanced capabilities for drug screening and evaluation, delivering a more precise assessment of drug efficacy and safety compared to traditional in vitro methods. This study demonstrates the efficacy of flavonoids in influencing osteogenic processes in BMSCs primarily through the Wnt/β-catenin pathway. These results uncover the potential of flavonoids as therapeutic medicine for treating periodontitis, meriting further research and development. [ABSTRACT FROM AUTHOR]

Objective(s): Quercetin is a plant flavonoid known for its pharmacological activities, such as antioxidant, anti-inflammatory, and anti-cancer properties. However, there is limited information available regarding its potential toxicities. A previous study showed that quercetin can inhibit human ether-a-go-related gene (hERG, also named KCNH2) currents, which may lead to long QT syndrome, torsade de pointes (TdP), and even sudden cardiac death. This study aimed to investigate the effects of quercetin on hERG and its potential mechanism. Materials and Methods: hERG currents and action potential duration (APD) were assessed using the patch clamp technique. Molecular docking was employed to elucidate the binding sites between quercetin and hERG. Transfection of wild-type or mutant plasmids was used to verify the results of molecular docking. Western blot was performed to determine the expression levels of hERG, transcription factor SP1, molecular chaperones HSP70 and HSP90, phosphorylated E3 ubiquitin ligase p-Nedd4-2, serum- and glucocorticoid-inducible kinase (SGK1), and phosphatidylinositol 3-kinase (PI3K). Immunoprecipitation was conducted to evaluate hERG ubiquitination. Results: Quercetin acutely blocked hERG current by binding to F656 amino acid residue, subsequently accelerating channel inactivation. Long-term incubation of quercetin accelerates Nedd4-2-mediated ubiquitination degradation of hERG channels by inhibiting the PI3K/SGK1 signaling pathway. Moreover, the APD of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) is significantly prolonged by 30 µM quercetin. Conclusion: Quercetin has a potential risk of proarrhythmia, which provided useful information for the usage and development of quercetin as a medication. [ABSTRACT FROM AUTHOR]

Toxocariasis is a zoonotic parasitic infection with worldwide distribution and high impact on human health. It has a limited clinical resolution with the available drugs, making it challenging to treat. Quercetin, which possesses biological and pharmacological qualities including antiparasitic, antioxidant, and anticancer activities, is a possible substitute for the current medications. Marine invertebrates can produce a vast array of different molecules, many of which are biologically active substances with distinct characteristics. In this study, we assessed the in vitro nematocidal effect of both quercetin and venom of Cassiopea andromeda Research highlights: Biological activity of quercetin could be used as chemotherapy for larval stages of parasitic nematode.Bioactive products in jellyfish venom is positively affect the larval stage of Toxocara. [ABSTRACT FROM AUTHOR]

The current study focused on the formulation and physical characterization of quercetin-loaded gelatin microspheres and their evaluation for potential use in drug delivery. For the experiment, gelatin microspheres (GM0—with gelatin alone, and GM1, GM2, and GM3—with different concentrations quercetin) were prepared. The physical characterization of microspheres was done using appropriate techniques. The suitability of a chosen formulation was adjudged by Fourier transform infrared spectroscopy (FTIR), loose surface crystal study and equilibrium swelling study along with the in vitro drug delivery potential. The formulated microsphere sample, GM2 with an optimum quantity of the drug quercetin (380 mg per 1500 mg gelatin), showed comparable but slightly better physical and rheological properties than the other two samples facilitating better flow and packaging properties. FTIR analysis revealed the absence of interference between the drug and the gelatin coating matrix and exhibited minimum drug coating. Also, GM2 showed a more controlled drug release profile in the dissolution media (acidic and basic). [ABSTRACT FROM AUTHOR]

Quercetin has shown potential antihypertensive‐like activities in several studies. The present study aimed to test the effect of quercetin supplementation on kidney damage and long‐term prognosis in hypertensive patients. The data of enrolled hypertensive patients were acquired from the NHANES dataset. The flavanol intake data was extracted from the FNDDS flavonoid database. Information regarding mortality was extracted from the NCHS. A total of 5801 hypertensive patients were included in this study. Preliminary analysis found that the total flavanols intake dosage was the independent influence factor of the kidney damage prevalence in hypertension, and it was found that only the quercetin supplementation was the protective factor for kidney damage after stratification analysis. For every 10 mg/d increase in quercetin intake, the kidney damage prevalence decreased by 8% [OR = 0.92, 95% CI: 0.85–0.99, p = 0.032]. The comprehensive analysis results suggested that hypertensive patients in the quercetin‐high group had a lower kidney damage prevalence and a higher survival probability than those in the quercetin‐low group. The urine microalbumin of hypertensive patients in the quercetin‐high group was significantly lower than that of hypertensive patients in the quercetin‐low group. In addition, at a median follow‐up time of 122 months, the mortality decreased by 9% [HR = 0.91, 95% CI: 0.84–0.99, p = 0.031] for every 10 mg/d increase in quercetin intake. The findings suggested that high quercetin intake was associated with low kidney damage prevalence and high survival probability. Based on the existing evidence, promoting quercetin supplementation as a supplementary treatment for hypertensive patients was warranted. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves' extracts contain high amounts of flavonoids and terpenoids, endowed with several beneficial effects. However, its anticancer activity towards colorectal cancer (CRC) has not been investigated in depth. Methods: The effect of a methanolic extract of D. kaki leaves, rich in kaempferol and quercetin derivatives, have been evaluated on an E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS-activating mutation. Results: This extract is effective in reducing tumor cells' viability without affecting the healthy mucosa cell line CCD 841. In fact, Western blot experiments showed its ability to induce apoptosis in cancer cells by increasing oxidative stress and disrupting mitochondrial functionality, as shown by reactive oxygen species measurement and Seahorse analysis. Conclusions: With the aim of increasing healthspan, as well as the substantial societal and macroeconomic costs associated with cancer, our results could pave the way to a role for D. kaki extract in both CRC treatment and prevention. [ABSTRACT FROM AUTHOR]

Background: Obesogenic diets cause intestinal inflammation and dysfunction. Polyphenols have shown a positive impact on reducing inflammation in in vitro studies. However, their bioactivity may not be the same in the in vivo system due to structural alteration by the gastrointestinal digestive process. The purpose of this study was to investigate the anti-inflammatory effect of onion peel and its major bioactive compound, quercetin, in the intestine and further examine the impact of intestinal digestion on this effect. Methods: Onion peel extract (OPE) and quercetin (Q) were digested using gastrointestinal digestive enzymes in vitro and then treated into lipopolysaccharide (LPS)-stimulated Caco-2/HT-29 cells. Genes and proteins related to tight junction, inflammation, and epithelial integrity were measured. Results: OPE and digested OPE (DOPE) had a higher protective effect on LPS-induced tight junction and inflammatory genes and paracellular permeability than Q and digested Q (DQ). DOPE was more effective than OPE, while digestion did not change the activity of Q. The anti-inflammatory effect of OPE and Q with or without digestion was achieved by inhibiting nuclear factor kappa B through AMP-activated protein kinase-activated silent mating-type information regulation 2 homolog 1. Conclusions: It was the first to find that a crude extract, after undergoing gastrointestinal digestion, demonstrated a notably superior anti-inflammatory effect in the cell study, suggesting the consumption of onion peels could potentially yield similar benefits in the human intestine. This discovery underscores the potential of onion peel polyphenols in combating intestinal inflammation, making them a compelling area of research for future therapeutic applications using food byproducts. [ABSTRACT FROM AUTHOR]

Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200 nm, meanwhile induce the generation of supersaturated quercetin solution more than 12 h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids. Quercetin supersaturated drug delivery system (QSDDS) using PVP K30 as precipitation inhibitor can maintain supersaturation and increase the oral bioavailability of free quercetin in plasma(by Figdraw) [ABSTRACT FROM AUTHOR]

To explore the potential mechanisms of Houttuynia cordata in the treatment of CRC using network pharmacology combined with experimental validation. The major active components of Houttuynia cordata were identified using the TCMSP database, and their related targets were mined. CRC-related target genes were obtained through the Genecards and OMIM databases. The R software Ven Diagram package was used for visualization of the intersection of drug and disease targets. The intersection target genes were subjected to GO function enrichment and KEGG pathway enrichment analysis using the R software clusterProfiler package. A "Drug - active component - target - Disease" network was constructed and analyzed using Cytoscape software. Intersection target genes were uploaded to the STRING database, and the resultant data were imported into Cytoscape software to construct a PPI network and filter core target genes. Expression analysis, diagnostic efficacy, and survival analysis were used to demonstrate the function and clinical value of the core target genes. The correlation between core genes in CRC samples and immune cell infiltration was analyzed using the R software and ssGSVA algorithm. Molecular docking validation of core active components with core target genes was performed using AutodockVina 1.2.2 software. Finally, the effects of quercetin and kaempferol, core active components of Houttuynia cordata, on the growth of HCT116 cells and the regulation of core target genes were validated through CCK8 assay, flow cytometry, and RT-qPCR. Seven effective active components and 147 component-related targets were selected, along with 3806 CRC-related target genes. GO analysis mainly involved biological processes such as epithelial cell proliferation, with KEGG pathway analysis focusing on pathways including AGE-RAGE signaling. Quercetin and kaempferol were identified as two core components, with IL1B, MMP9, CXCL8, and IL6 as four core target genes. Immune infiltration analysis showed that IL1B, MMP9, CXCL8, and IL6 primarily exert anti-CRC effects by promoting neutrophil activity. Molecular docking results indicated stable binding capacities of quercetin and kaempferol with IL1B, MMP9, CXCL8, and IL6. Experimental validation showed that quercetin and kaempferol could inhibit the viability of HCT116 cells in a dose-dependent manner, promote apoptosis, and downregulate the expression of IL1B, MMP9, CXCL8, and IL6 genes. Houttuynia cordata may exert therapeutic effects on CRC by modulating the immune microenvironment and anti-inflammatory responses, providing new research directions and theoretical guidance for the treatment of CRC with Houttuynia cordata. [ABSTRACT FROM AUTHOR]

Breast cancer remains a significant global health challenge, demanding innovative therapeutic approaches. Polyphenols, a class of natural compounds widely distributed in fruits, vegetables, and beverages, possess robust antioxidant and anti-inflammatory properties. They exhibit the potential to mitigate cancer cell proliferation and induce apoptosis. Nevertheless, their clinical utility is impeded by limited bioavailability and stability issues. These impediments find a solution through the advent of nanotechnology. Nano-carriers, owing to their diminutive dimensions and distinctive attributes, hold promise in enhancing the delivery of polyphenols to tumor sites, thereby augmenting bioavailability and therapeutic efficacy. Various nano-carriers, including liposomes, polymeric nanoparticles, and solid lipid nanoparticles, have been explored for polyphenol transport. These carriers safeguard polyphenols from degradation and enhance their solubility, facilitating targeted delivery to tumor sites and potentially reducing systemic adverse effects. This comprehensive review provides an in-depth examination of the current state of polyphenol-loaded nano-carriers in breast cancer therapy. It elucidates their potential as an innovative and precision-focused therapeutic modality to improve patient outcomes while mitigating side effects. [ABSTRACT FROM AUTHOR]

Aim: The therapeutic potential of senolytic drugs in osteoarthritis (OA) is poorly known. Quercetin, a senolytic agent exhibits promising potential to treat OA, having limited bioavailability. We investigated the effects of Quercetin-loaded nanoparticles (Q-NP) with enhanced bioavailability in human chondrocytes mimicking OA phenotype. Materials & methods: The C-20/A4 chondrocytes were exposed to ferric ammonium citrate to induce OA phenotype, followed by treatment with free Quercetin/Q-NP for 24 and 48-h. Q-NP were synthesized by nanoprecipitation method. Following treatment chondrocytes were assessed for drug cellular bioavailability, viability, cell cycle, apoptosis, oxidative stress and expression of key senescence markers. Results: Q-NP exhibited 120.1 ± 1.2 nm particle size, 81 ± 2.4% encapsulation efficiency, increased cellular bioavailability and selective apoptosis of senescent chondrocytes compared with free Quercetin. Q-NP treatment also induced oxidative stress and reduced the expressions of senescence markers, including TRB3, p16, p62 and p21 suggesting their ability to eliminate senescent cells. Last, Q-NP arrested the cell cycle in the sub-G0 phase, potentially creating a beneficial environment for tissue repair. Conclusion: Q-NP propose a promising delivery system for treating OA by eliminating senescent chondrocytes through apoptosis. Furthermore, their enhanced cellular bioavailability and capacity to modify cell cycle and senescent pathways warrant further investigations. Graphical Abstract Article highlights Quercetin-loaded nanoparticles (Q-NP) were successfully produced with a small, uniform size (120 nm) and a negative surface charge (-26.8 mV), indicating stability and potential for drug delivery. Over 81% of Quercetin, a poorly soluble drug, was encapsulated within the nanoparticles, suggesting efficient loading. Scanning electron microscopy revealed Q-NP with a smooth, spherical shape, ideal for drug entrapment. Compared with free Quercetin, Q-NP significantly increased Quercetin's solubility within the first 3 h, demonstrating enhanced drug delivery potential. Surprisingly Q-NP showed reduced cell viability compared with free Quercetin. Initially, Q-NP increased reactive oxygen species (ROS) production, a sign of oxidative stress, but levels decreased after 48 h compared with free Quercetin. Q-NP effectively reduced markers of cellular senescence compared with free Quercetin, suggesting a long-term protective effect. Q-NP caused cell cycle arrest, potentially preventing further damage from iron overload. Q-NP increased the number of pro-apoptotic cells compared with controls, suggesting they trigger programmed cell death in damaged cells. While Q-NP demonstrated positive effects in reducing senescence and promoting cell cycle arrest, the initial increase in ROS and the unexpected impact on cell viability require further exploration. [ABSTRACT FROM AUTHOR]