μM Of Quercetin Research Articles

Optimization of Particle Size Distribution with Gaussian Analysis of Albumin Microcarriers Cross-linked by Natural Phenolic Compounds

The biodegradation of albumin into natural products and nontoxicity besides its antigenicity has many advantages in controlled drug delivery of therapeutic agents. A bifunctional covalent bonding agent, glutaraldehyde is extensively used for linking amine groups of albümin microparticles/microcarriers (AlbMC’s). But its cytotoxicity and the rapid calcification of the glutaraldehyde-treated tissue limit the use of glutaraldehyde. Phenolic compound showed non-covalent and covalent chemical interactions with proteins. The objective of this research is to prepare three different natural phenolic compound cross-linked/stabilized AlbMC’s and estimate the cross-linker concentration which is giving narrow size distributions since it is important to gain higher surface area. The influence of qallic acid (GA), tannic acid (TA) and quercetin concentrations on AlbMC’s size was investigated by Gaussian function analysis of microcarriers determined after optical micrograph measurements. Gallic acid (GA) stabilized AlbMC’s have 3.35  0.71 μm average mean size distribution while it was 3.56  0.71 μm for Quercetin and 3.71  0.69 μm for TA stabilized microcarrier formations. Average mean particle size distribution of AlbMC’s synthesized with synthetic cross-linker, glutaraldehyde was calculated as 5.12  0.50 μm. All statistical analysis were evaluated by MATLAB program. New approach for albumin microcarrier synthesis by using phenolic compounds as a cross-linker can be proposed as an alternative microcarrier preparation system with narrow size distributions.

(S)-specific carbonyl reductase from Candida parapsilosis ATCC 7330 as a model for the initial screening of inhibitors for human carbonyl reductase

Human carbonyl reductase (CBR1) reduces carbonyl groups in drug molecules, particularly anticancer drugs, leading to altered pharmacological effects. This study reports a simple and efficient system that utilizes enzymes isolated from yeast as a model for the initial screening of inhibitors for human carbonyl reductases, offering a viable process for large scale applications. A purified stereospecific enzyme, (S)-specific carbonyl reductase from Candida parapsilosis ATCC 7330 (SRED), was employed whose crystal structure, PDB ID: 3CTM (100 % sequence identity with SRED) showed 27 % similarity with CBR1 (PDB ID: 1WMA). Furthermore, it was found to have a similarity for reaction with isatin and inhibition with quercetin (non-competitive) as in CBR1. Isatin as substrate showed a Km of 5.3 ± 1.08 mM, and Ki of 15.2 ± 1.64 µM for quercetin as inhibitor. Using (S)-specific carbonyl reductase model enzyme, a novel inhibitor, ethyl (E)−4-(4-chlorophenyl)−2-oxobut-3-enoate (ECOB) was identified. ECOB showed mixed inhibition for isatin reduction, with a Ki of 14.87 ± 0.78 µM and KI of 5.02 ± 0.02 µM respectively. Circular dichroism and molecular modelling studies supported the inhibitor studies. ECOB showed a lower IC50 value of 7.2 µM, as compared to the standard inhibitor quercetin (11.7 µM), hence a better inhibitor than quercetin.

Quercetin-loaded solid lipid nanoparticles exhibit antitumor activity and suppress the proliferation of triple-negative MDA-MB 231 breast cancer cells: implications for invasive breast cancer treatment.

Quercetin (QC) is a naturally occurring flavonoid found in abundance in fruits and vegetables. Its anti-cancer and anti-inflammatory properties have been previously demonstrated, but its low bioavailability hampers its clinical use. Triple-negative breast cancer is a subtype of breast cancer with a poor response to chemotherapy. This study investigates the anti-cancer effects of quercetin-solid lipid nanoparticles (QC-SLN) on the triple-negative breast cancer cell line MDA-MB231. MCF-7 and MDA-MB231 cells were treated with 18.9 µM of QC and QC-SLN for 48h. Cell viability, apoptosis, colony formation assay, and the anti-angiogenic effects of the treatment were evaluated. QC-SLN displayed optimal properties (particle size of 154nm, zeta potential of -27.7 mV, encapsulation efficiency of 99.6%, and drug loading of 1.81%) and exhibited sustained release of QC over 72h. Compared to the QC group, the QC-SLN group showed a significant decrease in cell viability, colony formation, angiogenesis, and a substantial increase in apoptosis through the modulation of Bax and Bcl-2 at both gene and protein levels. The augmentation in the proportion of cleaved-to-pro caspases 3 and 9, as well as poly (ADP-ribose) polymerase (PARP), under the influence of QC-SLN, was conspicuously observed in both cancer cell lines. This study showcases quercetin-solid lipid nanoparticles (QC-SLN) as a promising therapy for triple-negative breast cancer. The optimized QC-SLN formulation improved physicochemical properties and sustained quercetin release, resulting in reduced cell viability, colony formation, angiogenesis, and increased apoptosis in the MDA-MB231 cell line. These effects were driven by modulating Bax and Bcl-2 expression, activating caspases 3 and 9, and poly (ADP-ribose) polymerase (PARP). Further in vivo studies are needed to confirm QC-SLN's efficacy and safety.

Effective inhibition of breast cancer stem cell properties by quercetin-loaded solid lipid nanoparticles via reduction of Smad2/Smad3 phosphorylation and β-catenin signaling pathway in triple-negative breast cancer

BackgroundThe presence of cancer stem cells (CSCs) is a major cause of resistance to cancer therapy and recurrence. Triple-negative breast cancer (TNBC) is a subtype that responds poorly to therapy, making it a significant global health issue. Quercetin (QC) has been shown to affect CSC viability, but its low bioavailability limits its clinical use. This study aims to increase the effectiveness of QC in inhibiting CSC generation by using solid lipid nanoparticles (SLNs) in MDA-MB231 cells. Materials and methodsAfter treating MCF-7 and MDA-MB231 cells with 18.9 μM and 13.4 μM of QC and QC-SLN for 48 h, respectively, cell viability, migration, sphere formation, protein expression of β-catenin, p-Smad 2 and 3, and gene expression of EMT and CSC markers were evaluated. ResultsThe QC-SLN with particle size of 154 nm, zeta potential of −27.7 mV, and encapsulation efficacy of 99.6% was found to be the most effective. Compared to QC, QC-SLN significantly reduced cell viability, migration, sphere formation, protein expression of β-catenin and p-Smad 2 and 3, and gene expression of CD44, zinc finger E-box binding homeobox 1 (ZEB1), vimentin, while increasing the gene expression of E-cadherin. ConclusionsOur findings demonstrate that SLNs improve the cytotoxic effect of QC in MDA-MB231 cells by increasing its bioavailability and inhibiting epithelial-mesenchymal transition (EMT), thereby effectively inhibiting CSC generation. Therefore, SLNs could be a promising new treatment for TNBC, but more in vivo studies are needed to confirm their efficacy.

Efficient “on–off” photo-electrochemical sensing platform based on titanium dioxide nanotube arrays decorated with silver doped tin oxide for ultra-sensitive quercetin detection

Quercetin, a bioflavonoid found in fruits and vegetables, is a potential anticancer compound with strong anticancer activity. Hence, a photo-electrochemical sensor was developed for the detection of quercetin. In the present work, silver doped tin oxide (Ag@SnO2) was engineered via a solvothermal method, and titanium dioxide nanotubes (TiO2 NTs) were synthesized through anodizing process. A nanohybrid of Ag@SnO2 and TiO2 NTs was used as an electrode modifier to fabricate the photo-electrochemical sensor for the photo-electrochemical determination of quercetin. The Ag@SnO2 exhibited high electrocatalytic activity and good stability. TiO2 NTs have a high surface-to-volume ratio and superior conductivity. Due to the synergistic effect of the Ag@SnO2 and TiO2 NTs, the developed photo-electrochemical sensing platform was employed to quantitatively determine quercetin with high stability and sensitivity. The superior sensing performance of the proposed sensing platform was confirmed based on the low limit of detection of 1.2 nM which depicted two linear ranges from 0.004 to 0.124 and 0.124 to 3.6 µM for quercetin. The main advantage of this specific, sensitive, and, simple method with a short analysis time was in determining quercetin in honey, tea, and golden delicious samples.

Molecular and cellular outcomes of quercetin actions on healthy and tumor osteoblasts

There is a global trend in the use of natural bioactive compounds to complement conventional therapies in bone diseases. In this work, we studied the effects of the phytoestrogen quercetin (QUE) in healthy and tumor osteoblasts. We found that QUE (1 μM, 48 h) significantly increased the cell number and the viability of healthy human osteoblasts (hFOB cells) determined by a trypan blue and a MTS assay, respectively, among other concentrations tested. In addition, wound healing and cellular adhesion assays also demonstrated that 1 μM of QUE significantly stimulated both parameters in osteoblasts. Moreover, osteoblast differentiation was also triggered by QUE in an osteogenic medium by measuring alkaline phosphatase activity, calcium deposition, and collagen levels. Herein, a concentration of 0.01 μM of QUE showed an increment in these differentiation markers and an activation of AKT/GSK3β/β-catenin pathway, determined by a Western blot analysis. In addition, immunocytochemistry and subcellular fraction studies indicated an increase of β-catenin localization in the plasma membrane after QUE treatment. Otherwise, QUE (20–100 μM) decreased the cell number and the viability in tumor osteoblasts (ROS 17/2.8 cells) after 48 h. Furthermore, QUE (100 μM) decreased AKT(Ser473) and the pro-apoptotic protein BAD(Ser136) phosphorylation. In addition, the ERK1/2 phosphorylation increased leading to osteosarcoma cell death since pre-treatment with the MEK inhibitor PD98059 had reverted QUE effect. Altogether, these results indicate that low concentrations of QUE stimulate osteoblastogenesis but have no effect on the growth of tumor osteoblast cells, for which only high concentrations are efficient.

Preparation of three dimensional flower-like cobalt phosphate as dual functional electrocatalyst for flavonoids sensing and supercapacitor applications

In this report, 3D flower-like cobalt phosphate (Co3(PO4)2, CPO) was prepared through a facile co-precipitation method towards voltammetric sensing of rutin (RU), quercetin (QCT) and also employed for supercapacitor application. The structural morphologies were analyzed by various analytical techniques. The Brunauer–Emmett–Teller analysis of CPO displays a specific surface area of 40.885 m2 g−1 and a mesopore volume of 0.0108 cm3 g−1, which provides more catalytic sites, and a good electron transfer pathway that leading to promote enhanced electrochemical performance for detection of RU, and QCT. The oxidation peak current demonstrated low detection limits of 0.009 μM for RU and 0.003 μM for QCT with broad linear concertation of RU and QCT were 0.02 → 121.62 μM, and 0.08 → 129.8 μM, respectively. The fabricated electrode shows a higher sensitivity of 1.352 and 3.847 μA μM−1 cm−2 for RU and QCT detection. The modified CPO/SPCE offers excellent selectivity, repeatability, reproducibility, and further monitoring for RU and QCT in spiked fruit samples showing applicable recoveries. The electrochemical supercapacitor was explored using a CPO/NF electrode that revealed high specific capacitance of 680 F g−1 at 1.0 A g−1, and good stability of 89.3% capacitance retention after 10000 cycles at 6.0 A g−1.

ANTI-COAGULANT PROPERTIES OF FLAVONOID COMPOUNDS: POTENTIAL STRUCTURE-FUNCTIONAL RELATIONSHIP

Objective: Flavonoids, naturally-occurring compounds in fruits and vegetables, possess anti-coagulant property. However, a very few studies wereattempted to understand how flavonoid structure influences its anti-coagulation property, such as clotting time. In this study, we investigatedstructurally similar flavonoid compounds which differ in the number of hydroxyl groups and compared their anti-coagulation properties.Methods: We selected and evaluated five flavonoid compounds, that is, chrysin, apigenin, luteolin, kaempferol, and quercetin, for their anti-coagulantproperties using in vitro prothrombin time (PT) assays and activated partial thromboplastin time (APTT) assay.Results: Our findings suggested that quercetin, kaempferol, and luteolin showed a significant anti-coagulant effect on APTT (p<0.05) in a dosedependentmanner. The dose of 500 μM quercetin showed potent prolong APTT with 37.43±1.60 s, followed by 500 μM of kaempferol and luteolin(34.63±1.29 s and 4.83±1.56 s, respectively). Furthermore, a combination of 500 μM of quercetin with 0.25 U/ml of heparin demonstrated prolongAPTT (52.16±5.18 s) when compared with individual effects of either 0.25 U/ml heparin (33.4±0.50 s) or 500 μM quercetin (37.43±1.62 s) alone.Conclusion: Our results demonstrated that numbers of the hydroxyl group on flavonoid compounds influence anti-coagulation properties. Inaddition, the prolonged APTT assay results suggested that quercetin, kaempferol, and luteolin could affect factors VIII, IX, XI, and XII of intrinsicpathway. Moreover, the synergistic effect of quercetin further enhances the heparin anti-coagulation effect. Based on our findings, we recommendthat the consumption of vegetables and fruits rich in quercetin, luteolin, and kaempferol could help prevent thrombotic stroke in high-risk patients.

Quercetin influences in vitro maturation, apoptosis and metabolically active mitochondria of goat oocytes.

SummaryThe present study aimed to investigate the effect of quercetin as an alternative antioxidant to cysteamine on in vitro maturation. Oocytes were collected from goat ovaries, destined for in vitro maturation and distributed into three groups: CIS group, oocytes were immersed in MIV base medium; in Groups Q4 and Q8, oocytes were immersed in the medium of the CIS group, adding 4 μM or 8 μM of quercetin, respectively, and cultured for 24 h at 38.5°C with 5% CO2. The CIS and Q4 groups presented the same percentage of expanded cumulus cells, but the per cent in the Q8 group was significantly lower than that of the other groups (P<0.05). The oocyte retraction rate in the Q8 group was higher (P<0.05) than in the CIS and Q4 groups. Treatment with 8 μM of quercetin presented a lower proportion of expanded oocytes than the CIS group and 4 μM of quercetin (P<0.05). The percentage of MII oocytes was higher in the Q4 group than in the CIS group (P<0.05), but the percentages in the CIS and Q8 groups were similar. The rate of apoptosis was higher in the CIS group than in the other groups (P<0.05). In addition, oocytes matured with 4 μM quercetin showed higher mitochondrial activity than matured oocytes in the CIS and Q8 groups (P<0.05). In conclusion, 4 μM of quercetin can be used as an alternative to cysteamine in the in vitro maturation of goat oocytes.

Glycosylated Flavonoids from Psidium guineense as Major Inhibitors of HIV-1 Replication in vitro

Flavonoids are present in practically all plants and many biological activities have been described for them. The flavonoid quercetin is a common molecule for which anti-HIV activity has been demonstrated. Avicularin and guajaverin are derivatives of quercetin with a glycoside substituent in their structure. In this work, a mixture of both derivatives was purified from an extract of Psidium guinense. The mixture exhibited activity against HIV-1 in vitro, with an IC50 of approximately 8.5 μg/mL, which compares favorably with the IC50 of 53 μg/mL of quercetin. The mixture also inhibited HIV-1 reverse transcriptase (RT), with an IC50 of 7.2 μM, compared to 0.6 μM for quercetin. These results are in agreement with the in silico prediction for the interaction of these flavonoids with RT and suggest that the glycosylic moiety could favor the transport of the compound into the cell. However, the glycosidic moiety might be cleaved intracellularly, being the resultant quercetin responsible for the antiviral activity.

Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells

The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction.

EFFECTS OF INHIBITORS ON HAEMOLYMPH PHENOLOXIDASE FROM ROSACEOUS BRANCH BORER, OSPHERANTERIA COERULESCENS (COLEOPTERA: CERAMBYCIDAE)

Abstract The rosaceous branch borer, Ospheranteria coerulescens, is an important pest of rosaceous trees. This insect feeds on the twigs and branches of living trees and causes their death. The characterization of the insect phenoloxidase (PO) is of interest when doing comparative investigations, and so that we may be able to understand its biochemical properties. When designing new methods of insect control such as the use of PO inhibitors, an understanding of the biochemical properties is fundamental. In this study, PO from hemolymph of the rosaceous branch borer was purified using ammonium sulfate precipitation, gel-filtration, and ion-exchange chromatography. The biochemical properties were characterized using l-dihydroxyphenylalanine (L-DOPA) as the specific substrate. The apparent molecular weights of the three isoforms of PO were determined by SDS-PAGE to be 85.23, 79.45, and 66.06 kDa. Optimal pH for PO activity was pH 8, and the optimal temperature was 45°C. Phenoloxidase lost less than 50% of its relative activity after a 60 min incubation at the optimal temperature. The effects of ions and chemical materials such as K+, Ba2+, Zn2+ and EDTA on PO showed that PO activity was strongly inhibited by Zn2+. The Michaelis constant (Km) and maximum velocity (Vmax) were 88.61 mM and 0.14 μmol/min, respectively. The inhibitory effects of kojic acid, 4-hexylresorsinol, and quercetin on PO were determined, and the IC50s (inhibitory concentration) were estimated as 23.31 for kojic acid, 35.75 for 4-hexylresorcinol, and 60.8 μM for quercetin. The inhibitory potency of kojic acid was 1.54 times higher than that of 4-hexylresorcinol and 2.58 times higher than that of quercetin. Phenoloxidase was effectively inhibited by 4-hexylresorcinol, and the inhibition type was competitive. The inhibition types of PO by kojic acid and quercetin were found to be mixed.

Separation/Determination of Flavonoids and Ascorbic Acid in Rat Serum and Excrement by Capillary Electrophoresis with Electrochemical Detection

A capillary electrophoresis with electrochemical detection was developed for the simultaneous determination of three flavonoids (naringenin, rutin, quercetin) and ascorbic acid. It was found that naringenin, rutin, quercetin and ascorbic acid were well separated within 5 min in borate buffer solution (pH 8.6, 24 mM). The detection limit was 1.0 microM for naringenin, 8.0 microM for rutin, 2.0 microM for ascorbic acid and 0.5 microM for quercetin. The protocol was successfully applied for the determination of the analytes in rat serum and excrement. Recovery results ranged from 90.9 to 108.6%.

Quercetin, Quercetrin Except Rutin Potentially Increased Pirarubicin Cytotoxicity by Non-Competitively Inhibiting the P-Glycoprotein-and MRP1 Function in Living K562/adr and GLC4/adr Cells

Problem statement: Quercetin and its glycoside derivatives are increasingly receiving interests as new generation of anticancer molecules and were recognized by multidrug resistant transporters such as P-glycoprotein and MRP1 protein. Of relevance to their use as anticancer agents alone or in combination with other agents, this study aims to analyze the interaction of the compounds with the MDR transporters including P-glycoprotein and MRP1 protein in living multidrug resistant cells. Approach: The potential MDR reversing action of flavonoids was assessed by using the co-treatment of anticancer drug, pirarubicin or daunorubicin and quercetin, quercetrin or rutin compared with the series of co-treatment of pirarubicin or daunorubicin and the known inhibitor such as cyclosporine A and verapamil. The evidence of direct interaction of molecules with MDR protein was investigated by measuring the ability of inhibition of the rate of P-glycoprotein- and MRP1-mediated efflux of pirarubicin out of cells. Results: Quercetin and its glycoside derivatives efficiently inhibited cancer cell proliferation and re-sensitize the MDR cells to pirarubicin but not for daunorubicin. Our results clearly show that quercetin, quercetrin except rutin non-competitively inhibited the function of P-glycoprotein in K562/adr and MRP1 in GLC4/adr cells. The determined KI value of P-glycoprotein was equal to 0.33 µM for quercetin and 1 µM for quercetrin and KI value of MRP1 was equal to 0.45 mM for quercetin and 0.5 mM for quercetrin. Conclusion: The overall results demonstrated that quercetin, quercetrin and rutin should be considered as potential pharmaceutical molecules that might be used as MDR inhibitors.

Simultaneous determination of quercetin, kaempferol and isorhamnetin accumulated human beast cancer cells, by high-performance liquid chromatography

Quercetin, kaempferol and isorhamnetin are the most important constituents in ginkgo flavonoids. A simple, rapid and sensitive high-performance liquid chromatography method was developed to simultaneously determine quercetin, kaempferol and isorhamnetin absorped by human breast cancer cells. Cells were treated with ginkgo flavonols and then lysed with Triton-X 100. The flavonols in the samples were measured by RP-HPLC with a C18 column after a simple extraction with a mixture of ether and acetone. The mobile phase contained phosphate buffer (pH 2.0; 10 mM) tetrahydrofuran, methanol and isopropanol (65:15:10:20, v/v/v/v). The ultraviolet detector was operated at 380 nm. The calibration curve was linear from 0.1 to 1.0 μM ( r > 0.999) for each flavonol. The mean extraction efficiency was about 70%. The recovery of the assay was between 98.9 and 100.6%. The limit of detection was 0.01 μM for quercetin and kaempferol and 0.05 μM for isorhamnetin. The limit of quantitation was 0.1 μM (R.S.D. < 10%) for each flavonol. The intra- and inter-day coefficients of variation were less than 10% (R.S.D.). The validated method was applied to quantify quercetin, kaempferol and isorhamnetin in human breast cancer Bcap37 and Bcap37/MDR1 cells.

Inhibition of Mammalian 15-Lipoxygenase-Dependent Lipid Peroxidation in Low-Density Lipoprotein by Quercetin and Quercetin Monoglucosides

Lipoxygenase is suggested to be involved in the early event of atherosclerosis by inducing plasma low-density lipoprotein (LDL) oxidation in the subendothelial space of the arterial wall. Since flavonoids such as quercetin are recognized as lipoxygenase inhibitors and they occur mainly in the glycoside form, we assessed the effect of quercetin and its glycosides (quercetin 3-O-β-glucopyranoside, Q3G; quercetin 4′-O-β-glucopyranoside, Q4′G; quercetin 7-O-β-glucopyranoside, Q7G) on rabbit reticulocyte 15-lipoxygenase (15-Lox)-induced human LDL lipid peroxidation and compared it with the inhibition obtained by ascorbic acid and α-tocopherol, the main water-soluble and lipid-soluble antioxidants in blood plasma, respectively. Quercetin inhibited the formation of cholesteryl ester hydroperoxides (CE-OOH) and endogenous α-tocopherol consumption effectively throughout the incubation period of 6 h. Ascorbic acid exhibited an effective inhibition only in the initial stage and LDL preloaded with fivefold α-tocopherol did not affect the formation of CE-OOH compared with the native LDL. CE-OOH formation was inhibited by both quercetin and quercetin monoglucosides in a concentration-dependent manner. Quercetin, Q3G, and Q7G exhibited a higher inhibitory effect than Q4′G (IC50: 0.3–0.5 μM for quercetin, Q3G, and Q7G and 1.2 μM for Q4′G). While endogenous α-tocopherol was completely depleted after 2 h of LDL oxidation, quercetin, Q7G, and Q3G prevented the consumption of α-tocopherol. Quercetin and its monoglucosides were also exhausted during the LDL oxidation. These results indicate that quercetin glycosides as well as its aglycone are capable of inhibiting lipoxygenase-induced LDL oxidation more efficiently than ascorbic acid and α-tocopherol.