Quercetin Complex Research Articles

Inclusion Complexes of Quercetin with β-Cyclodextrins: Ultraviolet and Infrared Spectroscopy and Quantum Chemical Modeling

The methods of ultraviolet and infrared spectroscopy and quantum chemical modeling have been used to evaluate the parameters of the formation of a supramolecular inclusion complex between the flavonoid quercetin and the hydroxypropyl-β-cyclodextrin molecular container. The solubility of quercetin in water has been shown to increase by a factor of more than 50 when included in a supramolecular complex with 16 mM hydroxypropyl-β-cyclodextrin. It has been demonstrated that bioavailability of quercetin is improved after encapsulation with hydroxypropyl-β-cyclodextrin. The association constant for the inclusion complex of quercetin and hydroxypropyl-β-cyclodextrin (1 : 1) has been evaluated by the Higuchi-Connors method to be 3275 ± 448 М–1. The formation of the inclusion complex results in considerable changes in the vibrational spectra of components compared to the spectrum of the physical mixture of quercetin and hydroxypropyl-β-cyclodextrin. This difference can be explained by structural changes of the components due to hydrogen bond formation. The molecular modeling of the inclusion complex has shown that the geometry and properties of the components change after encapsulation of quercetin molecule (“guest”) inside the cavity of β-cyclodextrins (“host”). The torsion angles between the rings of the planar quercetin molecule in the complexes with β-cyclodextrin and hydroxypropyl-β-cyclodextrin have been evaluated to be 149.5° and 138.7°, respectively.

Биофлавоноиды в лечении пациентов с сахарным диабетом 2-го типа и церебральным атеросклерозом

Цель работы — комплексная оценка влияния кверцетина на функциональное состояние центральной нервной и сердечно-сосудистой систем у больных ишемическим инсультом (ИИ) и сахарным диабетом 2-го типа (СД2) в восстановительный период. Материал и методы. В клинике ГУ «Институт геронтологии им. Д.Ф. Чеботарева НАМН Украины» проведено открытое пилотное когортное проспективное клиническое исследование, которое включало 30 больных, перенесших атеротромботический ишемический инсульт в каротидном бассейне (19 женщин и 11 мужчин), в возрасте от 55 до 75 лет (средний возраст 64,3±7,5 года), треть из них имели в анамнезе СД2. До и после курсового приема препарата кверцетин больным проводили комплексное клинико-неврологическое и нейропсихологическое обследование, исследование мозгового кровотока методом ультразвукового дуплексного сканирования экстра- и интракраниальных отделов магистральных артерий головы и шеи, электрокардиографию с оценкой вариабельности ритма сердца. Все больные получали кверцетин (лиофилизат для приготовления раствора для инъекций (комплекс кверцетина с повидоном) в дозе 0,5 г в сутки в течение 10 дней. Для приготовления раствора для внутривенного введения препарат растворяли в 100 мл изотонического раствора NaCl и вводили внутривенно капельно в течение 15-20 минут 1 раз в день. Результаты. У больных с левополушарным инсультом кверцетин оказывал более выраженное влияние на структуру биоэлектрической активности головного мозга и церебральную гемодинамику, чем у больных с правополушарной локализацией ИИ. У больных, перенесших ИИ, кверцетин улучшалпсихоэмоциональные и мнестические функции за счет положительной реорганизации биоэлектрической активности головного мозга, улучшения церебральной гемодинамики и гармонизации симпатического и парасимпатического звеньев вегетативной нервной системы. Выводы. Корригирующее влияние кверцетина на функциональное состояние мозга и сердца дает основание рекомендовать применение препарата в системе реабилитации больных, перенесших ишемический инсульт.

Elucidation of molecular interactions between human γD-crystallin and quercetin, an inhibitor against tryptophan oxidation

Different post-translational changes in eye lens crystallin proteins contribute towards the development of cataract. We have studied in vitro oxidative modification of tryptophan (Trp) residues of human γD-crystallin (HGD) towards formation of N-formylkynurenine (NFK) associated with cataractogenesis. This oxidation was found to be inhibited by quercetin at relatively low concentration. Interactions between quercetin and HGD were further studied using fluorescence techniques. Binding and quenching constants were determined as ∼104 M −1. Static quenching of fluorescence due to HGD–quercetin complex formation at ground state was confirmed by finding excited state life time of Trp residues. Energy transfer occurred between the protein and quercetin. Hydrogen bonding and/or van der Waals interactions were involved between HGD and quercetin. Synchronous and three-dimensional fluorescence along with far-UV CD studies suggested no major conformational alterations occurred in HGD due to quercetin binding. Experimental observations were supported by the docking results. Communicated by Ramaswamy H. Sarma

Zinc-quercetin complex: From determination to bioactivity

Flavonoids are a group of polyphenolic compounds widely present in the herbal world and playing an important role in the human diet. The flavanol quercetin makes up 70% of the total daily intake of flavonoids. Quercetin is able to complex with many metal ions, and it exhibits potent antioxidative ability. Using the equimolar solution variation method, it was confirmed that quercetin makes a complex with the zinc(II) ion at pH 5.25, in a stoichiometric ratio quercetin:zinc(II) ion = 2:1, with the absorption maximum l=363 nm. This fact was used to develop a simple, precise and accurate assay to determine the content of quercetin in various samples of heterogeneous composition. The proposed indirect spectrophotometric method can selectively determine quercetin in concentrations ranging from 0.1 to 6.0 mgL-1, with LOD and LOQ estimated as 0.03 mgL-1 and 0.1 mgL-1, respectively. The reliability of the proposed method was confirmed by a previously developed RP-HPLC/UV method. The proposed method was successfully used to determine the quercetin content in dietary supplement tablets, capsules and two onion extracts, with high reproducibility. The antioxidative ability of quercetin and the zinc(II)-quercetin complex was determined using DPPH and FRAP methods. The same samples were tested for antimicrobial activity against seven laboratory control strains of bacteria and one strain of yeast. As a result of those tests, there are no obstacles to combine quercetin and zinc in the same supplement formulation.

Exploring the interactions of a Tb(III)-quercetin complex with serum albumins (HSA and BSA): spectroscopic and molecular docking studies.

Serum albumins (human serum albumin (HSA) and bovine serum albumin (BSA), two main circulatory proteins), are globular and monomeric macromolecules in plasma that transport many drugs and compounds. In the present study, we investigated the interactions of the Tb(III)-quercetin (Tb-QUE) complex with HSA and BSA using common spectroscopic techniques and a molecular docking study. Fluorescence data revealed that the inherent fluorescence emission of HSA and BSA was markedly quenched by the Tb-QUE complex through a static quenching mechanism, confirming stable complex formation (a ground-state association) between albumins and Tb-QUE. Binding and thermodynamic parameters were obtained from the fluorescence spectra and the related equations at different temperatures under biological conditions. The binding constants (Kb ) were calculated to be 0.8547 × 103 M-1 for HSA and 0.1363 × 103 M-1 for BSA at 298 K. Also, the number of binding sites (n) of the HSA/BSA-Tb-QUE systems was obtained to be approximately 1. Thermodynamic data calculations along with molecular docking results indicated that electrostatic interactions have a main role in the binding process of the Tb-QUE complex with HSA/BSA. Furthermore, molecular docking outputs revealed that the Tb-QUE complex has high affinity to bind to subdomain IIA of HSA and BSA. Binding distances (r) between HSA-Tb-QUE and BSA-Tb-QUE systems were also calculated using the Forster (fluorescence resonance energy transfer) method. It is expected that this study will provide a pathway for designing new compounds with multiple beneficial effects on human health from the phenolic compounds family such as the Tb-QUE complex.

Synthesis of Quercetin-Metal Complexes, In Vitro and In Silico Anticholinesterase and Antioxidant Evaluation, and In Vivo Toxicological and Anxiolitic Activities.

The level of acetylcholine, a neurotransmitter essential for processing memory and learning, is lower in the brains of patients with Alzheimer's disease due to the higher concentration of the enzyme acetylcholinesterase. The main compounds used for Alzheimer's treatment are acetylcholinesterase inhibitors. Quercetin coordination complexes with the metal ions Cu+2, Zn+2, Ni+2, Co+2, and Fe+2 were synthesized to investigate their potential use against Alzheimer's disease, by evaluating the inhibition of acetylcholinesterase in vitro and in silico, as well as the antioxidant activity, toxicity, and anxiolytic action in the zebrafish (Danio rerio) model. The organic complexes were characterized by UV-Vis and FT-IR. The spectral information suggested that coordination of metals occurs with the carbonyl group and OH linked to the C-3 carbon of quercetin. The quercetin-Fe (QFe) complex presented the best antioxidant and antiacetylcholinesterase actions, and these results were confirmed by molecular docking. In the toxicity and locomotor evaluation, the quercetin molecules and the synthesized complexes, mainly QCu and QZn derivatives, showed the highest degree of inhibition of the fish's locomotor activity, suggesting a possible anxiolytic action. Then, quercetin complexes with metals, mainly with Fe+2, represent valuable compounds and deserve more investigation as promising agents against Alzheimer's disease.

A quercetin based fluorescent chemical sensor for ultra-sensitive determination and speciation of tungsten species in water.

The current study explores the use of quercetin for developing a highly selective spectrofluorimetric methodology for trace determination, speciation and thermodynamic characterization of tungstate (WO42-) species in water. The study relies on the principle of chelate formation between WO42- and quercetin with subsequent increase in the emission intensity. The developed method could be applied successfully in a wide linear range (1.0-400.0μgL-1) with a detection limit of 0.28μgL-1 and quantification limit of 0.92μgL-1 at λex/em=400/492nm. The developed method was successfully applied in real tap and waste water samples. The suitability of the proposed method was further validated by inductively coupled plasma-optical emission spectrometry (ICP-OES) in terms of student's t and F tests at 95% confidence. Characterization (NMR, FTIR and electronic spectra), stoichiometry, stability constant, fluorescence mechanism and thermodynamic parameters (ΔH, ΔS, and ΔG) of the produced complex species were evaluated and properly assigned. The fluorescence quenching mechanism of tungstate quercetin complex by Triton X-100 was also evaluated for computing Stern-Volmer quenching constant and approximating quenching sphere. The method showed a clear significance over most of the reported methods for tungsten in literature in terms of good accuracy, robustness, ruggedness, short analytical time and cost-effectiveness.

A Solid Dispersion of Quercetin Shows Enhanced Nrf2 Activation and Protective Effects against Oxidative Injury in a Mouse Model of Dry Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) represents a major reason for blindness in the elderly population. Oxidative stress is a predominant factor in the pathology of AMD. We previously evaluated the effects of phospholipid complex of quercetin (Q-PC) on oxidative injury in ARPE-19 cells, but the underlying mechanisms are not fully understood. Herein, the solid dispersion of quercetin-PC (Q-SD) was prepared with solubility being 235.54 μg/mL in water and 2.3×104 μg/mL in chloroform, which were significantly higher than that of quercetin (QT) and Q-PC. Q-SD also exhibited a considerably higher dissolution rate than QT and Q-PC. Additionally, Q-SD had Cmax of 4.143 μg/mL and AUC of 12.015 μg·h/mL in rats, suggesting better bioavailability than QT and Q-PC. Then, a mouse model of dry AMD (Nrf2 wild-type (WT) and Nrf2 knockout (KO)) was established for evaluating the effects of Q-SD in vivo. Q-SD more potently reduced retinal pigment epithelium sediments and Bruch's membrane thickness than QT and Q-PC at 200 mg/kg in Nrf2 WT mice and did not work in Nrf2 KO mice at the same dosage. Additionally, Q-SD significantly decreased ROS and MDA contents and restored SOD, GSH-PX, and CAT activities of serum and retinal tissues in Nrf2 WT mice, but not in Nrf2 KO mice. Furthermore, Q-SD more potently increased Nrf2 mRNA expression and stimulated its nuclear translocation in retinal tissues of Nrf2 WT mice. Q-SD significantly increased the expression of Nrf2 target genes HO-1, HQO-1, and GCL of retinal tissues in Nrf2 WT mice, not in Nrf2 KO mice. Altogether, Q-SD had improved physicochemical and pharmacokinetic properties compared to QT and Q-PC and exhibited more potent protective effects on retina oxidative injury in vivo. These effects were associated with activation of Nrf2 signaling and upregulation of antioxidant enzymes.

Antioxidant Activity and Hepatotoxicity of Flavonoids and Their Metal Complexes Through Co‐Administration of β‐Cyclodextrin

AbstractThe in vivo determination of radical scavenging activity of flavonoids (Fls) and their metal complexes (M‐Fls) through co‐administration of 2‐hydroxypropyl beta‐cyclodextrin (HP‐βCD) was determined. The flavonoids morin (mo), quercetin (quer), primuletin (prim), their Cu (II) and Fe (III) complexes were selected to explore their radical scavenging potential. Metal complexes of flavonoids (M‐Fls) showed better radical scavenging activity RSA when injected to rats than corresponding flavonoids. The RSA is improved in the presence of HP‐βCD. This increase in RSA was assisted by enhanced enzymatic activity of catalase (CAT) and superoxide dismutase (SOD) activity. The compounds displayed hepatoprotection against alloxan induced liver damage as flavonoid injected group displayed lower levels of enzymes and intermediates aspartate/alanine transaminase (AST), alanine aminotransferase (ALT), Lipid peroxidation (MDA), Hydroxyproline (HYP), Sailic acid (SA) and higher albumin and total proteins level compared with alloxan treated group. It was evaluated by histopathological investigations that M‐Fls restored the hepatic damage caused by alloxan. The binding constants values of the compounds with human plasma (n‐HP) revealed the order of 103‐104 L−1. The binding interactions of the compounds with human plasma in the presence of HP‐βCD is decreased which in turns increased the RSA as well as CAT and SOD activities. Based upon our results, it was concluded that radical scavenging activities and hepatoprotective activities of M‐Fls is increased when co‐administrated with HP‐βCD.

Investigation of Chitosan, Quercetin and Water Interactions using Free Energy Calculations and Molecular Docking

Predicting the preferred orientation of a ligand to a receptor and the free energy (ΔG AB ) of these molecules in a solution is very useful for pharmaceutical applications. In this work, ΔG AB between chitosan and quercetin molecules with water were obtained by the thermodynamic integration (TI) method and the chitosan+quercetin complex was investigated by Molecular Docking (MDK). The topology of the molecules was compatible with the CHARMM force-field. Both molecules were solvated with the GROMACS SPC water model. The ΔG AB values of the molecule+water systems with the thermodynamic integration (TI) method was done in a 10 ns simulation. The complex was achieved in a 2.5 nm x 2.5 nm x 2.5 nm box. The ΔG AB values for the molecules+water systems were 14.36 +/- 0.46 and 0.19 +/- 0.53 kJ/mol, respectively. For the complex, nine conformations were obtained for the quercetin around the chitosan. The best conformation showed an affinity energy of -3.8 kcal/mol. The ΔG AB results for the systems confirm the low or no solubility of the molecules in the water under normal conditions, as already demonstrated experimentally. The docking showed that the interaction between chitosan and quercetin molecules involves hydrogen bonds in a specific position. DOI: http://dx.doi.org/10.17807/orbital.v11i2.1344

EFFECT OF A WATER-SOLUBLE FORM OF QUERCETIN ON THE DISINTEGRATION OF PERIODONTAL ORGANIC MATRIX IN RATS EXPOSED TO THE SYSTEMIC ADMINISTRATION OF SALMONELLA TYPHI LIPOPOLYSACCHARIDE

The experiment on 30 white rats was designed to investigate the effect of a water-soluble form of quercetin on collagenolysis and depolymerization of proteoglycans and glycoproteins in both soft and bone tissues of periodontium under the conditions of systemic administration of S. typhi lipopolysaccharide. The animals were divided into 3 groups: the 1st group included intact animals, the 2nd group involved the animals exposed to the systemic administration of S. typhi lipopolysaccharide (pyrogenal), the 3rd group was made up the rats, which were given a water-soluble complex of quercetin and polyvinylpyrrolidone (corvitin) intraperitoneally in a dose of 500 mg / kg (10 mg / kg in terms of quercetin) every 3 days, starting from the 30th day of the experiment. The latter was administered in a dose of 0.4 μg/kg 3 times during the 1st week and once a week for the next 7 weeks. Collagenolysis was assessed by the concentration of free hydroxyproline; the level of depolymerisation of proteoglycans and glycoproteins was assessed by the content of glycosaminoglycans (GAGs) and N-acetylneuraminic acid (NANA) respectively. The introduction of quercetin in the experimental conditions significantly reduced the concentration of free hydroxyproline in soft and bone periodontal tissues by 27.3 and 26.7%, GAG – by 36.3 and 39.9%, and NANA – by 17.6 and 46.8%, respectively compared to the values of the 2nd group. The coefficient of root exposure in molars was inferior to the findings in the group with the modelled systemic inflammatory response by 26.9%. It can be concluded that the use of quercetin in the systemic lipopolysaccharide administration significantly reduces the depolymerisation of the components of the organic matrix in soft and bone periodontal tissues (collagen, proteoglycans and sialoglycoproteins), and limits the resorption of the alveolar process in jaws.

Synthesis, Characterization, and Biomedical Applications of an Alkylated Quercetin-Gadolinium Complex.

Flavonoids and their derivatives have been extensively studied for their pharmaceutical applications due to their antioxidant and anti-inflammatory properties. The coordination complexes of several flavonoids have demonstrated DNA binding ability that can confer anticancer properties. The structure of the flavonoid has a pronounced influence on its pharmacological properties. Herein we report the synthesis and characterization of alkylated quercetin and its complex with gadolinium. The structure of the complex was confirmed using spectroscopic techniques. The ability of the gadolinium-alkylated quercetin complex to serve as a magnetic contrast agent was compared with gadolinium-quercetin complex. The quercetin-gadolinium complex was found to exhibit better contrast property with a relaxivity of 0.2952 μg mL-1 s-1 when compared to the gadolinium complex of alkylated quercetin. This difference primarily arises due to the greater hydrophobicity of the alkylated quercetin complex that restricts access of water. However, the alkylated quercetin was found to exhibit better enzyme mimic activity as the metal ion served as a redox center that enabled quantification of hydrogen peroxide in the concentration range 50-450 μM within 5 s with a sensitivity of 64 nA/μM and limit of detection of 7.3 μM. The better sensing performance of the alkylated quercetin-gadolinium complex, reported here for the first time, when compared to quercetin-gadolinium complex can be attributed to the enhanced electroactive area on the working electrode.

Quercetin and its Complex with Cyclodextrin against Oxidative Damage of Mitochondria and Erythrocytes: Experimental Results in vitro and Quantum-Chemical Calculations

Abstract—In this work, we compared the efficacy of quercetin, one of the best known and widely investigated flavonoids, and the inclusion complex of quercetin and hydroxypropyl−β-cyclodextrin in prevention of disturbances in redox balance of rat liver mitochondria and erythrocytes during oxidative stress and regulation of the process of the mitochondrial permeability transition pore formations in vitro and theoretically calculated the structure of quercetin and its oxidative forms, as well as their molecular electronic properties. Quercetin (5–100 μM) inhibited membrane lipid peroxidation and reduced glutathione oxidation dose dependently in both rat liver mitochondria and erythrocytes during exposure to tert-butyl hydroperoxide (700 μM). Simultaneously, quercetin (25 μM) stimulated the Ca2+-induced mitochondrial permeability transition pore formations and inhibited this process at higher concentrations (100 mM). The incorporation of quercetin in the supramolecular complex with hydroxypropyl−β-cyclodextrin enhanced its antioxidative activity, first of all, in the cytoplasm of the cell and mitochondrial matrix. Molecules of quercetin, semiquinone radicals, and stable products formed in the oxidation, ortho- and p-quinone methide, have a planar structure. The calculated value of the dipole moment of the quercetin molecule is 4.34 D. The quercetin molecule is thermodynamically more stable than the products of its oxidation, among which p-quinone methide-III is the most stable form.

Determination of flavonoids and total polyphenol contents in commercial apple juices

We propose a sensitive and selective spectrofluorimetric method for the determination of flavonoids as expressed in ‘quercetin equivalent’ in apple juices. The method is based on the strong emission of the aluminium(III)-quercetin complex at 480 nm with excitation at 420 nm, and it is successfully applied for the determination of flavonoids in commercial apple juices and compared with results obtained in reference spectrophotometric determination. The flavonoid content in commercial apple juices was found to range from 5.53 to 15.55 mg/l quercetin equivalent. The very good agreement between the two methods indicates the suitability of the proposed spectrofluorimetric method for the precise and accurate determination of flavonoids. In addition, the total polyphenol content was determined spectrophotometrically using the Folin-Ciocalteu (FC) method and the antioxidative activity of the tested juices was tested in a DPPH assay and these values were correlated with each other. The obtained profiles of compounds with antioxidative ability lead us to conclude that fruit juice labels based only on fruit % might sometimes misinform consumers.

Exploring the oxidation and iron binding profile of a cyclodextrin encapsulated quercetin complex unveiled a controlled complex dissociation through a chemical stimulus

BackgroundFlavonoids possess a rich polypharmacological profile and their biological role is linked to their oxidation state protecting DNA from oxidative stress damage. However, their bioavailability is hampered due to their poor aqueous solubility. This can be surpassed through encapsulation to supramolecular carriers as cyclodextrin (CD). A quercetin- 2HP-β-CD complex has been formerly reported by us. However, once the flavonoid is in its 2HP-β-CD encapsulated state its oxidation potential, its decomplexation mechanism, its potential to protect DNA damage from oxidative stress remained elusive. To unveil this, an array of biophysical techniques was used. MethodsThe quercetin-2HP-β-CD complex was evaluated through solubility and dissolution experiments, electrochemical and spectroelectrochemical studies (Cyclic Voltammetry), UV–Vis spectroscopy, HPLC-ESI-MS/MS and HPLC-DAD, fluorescence spectroscopy, NMR Spectroscopy, theoretical calculations (density functional theory (DFT)) and biological evaluation of the protection offered against H2O2-induced DNA damage. ResultsEncapsulation of quercetin inside the supramolecule's cavity enhanced its solubility and retained its oxidation profile. Although the protective ability of the quercetin-2HP-β-CD complex against H2O2 was diminished, iron serves as a chemical stimulus to dissociate the complex and release quercetin. ConclusionsWe found that in a quercetin-2HP-β-CD inclusion complex quercetin retains its oxidation profile similarly to its native state, while iron can operate as a chemical stimulus to release quercetin from its host cavity. General significanceThe oxidation profile of a natural product once it is encapsulated in a supramolecular carrier was unveiled as also it was discovered that decomplexation can be triggered by a chemical stimilus.

Vanadium quercetin complex attenuates mammary cancer by regulating the P53, Akt/mTOR pathway and downregulates cellular proliferation correlated with increased apoptotic events.

Flavonoid metal ion complexes have been deliberated in recent years and are considered as a new class of medicinal agents with enhanced therapeutic activity and low toxicity. Our study deals with chemotherapeutic effects of vanadium, when coordinated with the flavonoid quercetin on a defined model of chemically induced rat mammary carcinogenesis in vivo and on human breast cancer cell line MCF-7 in vitro. The characterization of the complex was achieved through UV-Visible, IR, and Mass spectra and antioxidant activity was assessed by DPPH, FRAP and ABTS methods. In vitro studies established that the complex upregulated the expressions of p53, Caspase 3 and 9, whereas down regulating Akt, mTOR and VEGF expressions and also induced apoptosis and DNA fragmentation in a dose dependent manner. Acute and Sub-acute toxicity was performed to determine safe doses. 7,12-Dimethylbenz(α)anthracene (0.5mg/100g body weight) was used for induction of breast cancer in female Sprague-Dawley rats via single tail vein injection. The histopathological analysis after 24weeks of carcinogenesis study depicted substantial repair of hyperplastic lesions. TUNEL assay showed an increase in apoptotic index (0.14 ± 0.03; 0.15 ± 0.01) in vanadium-quercetin treated groups as compared to the carcinogen control (0.02 ± 0.01) along with upregulation of Bcl-2 and downregulation of Bax and p53. Immunohistochemical analysis also exhibited decrease in cell proliferation in the vanadium-quercetin treated groups (11.3 ± 0.12; 11.8 ± 0.10). Thus, results from both in vivo and in vitro studies revealed that vanadium-quercetin complex could be a potential candidate for development of approved drug for breast cancer in the near future.

Theoretical investigation of the superoxide anion free radical elimination by quercetin–metal complexes

The elimination of superoxide anion free radical O 2 ·− by the complexes of quercetin and physiological metal ions has been investigated theoretically. It turns out that Ca(II) and Zn(II) quercetin complexes are mild and efficient reagent on O 2 ·− fixing, and Fe(II) and Ni(II) quercetin complexes are excellent reagent on O 2 ·− elimination, and Cu(II) and Co(II) quercetin complexes are mainly no effect on O 2 ·− , which is consistent with some experiments, and Cu(I) and Co(I) complexes are active on O 2 ·− elimination on some sites of –OH. Some metal ion complexes herein only have one active center on metal ion itself, and none of their OH sites is active on O 2 ·− fixing such as Cr(III) and Fe(III) and Mn(II). The possible transition states of the interaction between quercetin molecule and O 2 ·− on different OH sites also have been investigated. We get the similar transition states for different OH sites, the activation energy is heavily high from reactants to transition states, and the transition states are near to the final products, which indicates that though the quercetin molecule can eliminate O 2 ·− , metal ions quercetin complexes are quite good at it, and some complexes can eliminate more than one O 2 ·− at the same time, which may be the potential effective medicines for O 2 ·− elimination to protect β cells from O 2 ·− attacking and helpful for diabetics and other relative diseases.

Interaction of flavonols with human serum albumin: a biophysical study showing structure–activity relationship and enhancement when coated on silver nanoparticles

Binding affinities of flavonols namely quercetin, myricetin, and kaempferol to human serum albumin (HSA) were determined fluorimetrically and the order was observed to be myricetin > quercetin > kaempferol demonstrating structure–activity relationship. Quercetin-coated silver nanoparticles (AgNPs) show higher binding affinity to HSA compared to free quercetin with binding constants 6.04 × 107 M−1 and 4.2 × 106 M−1, respectively. Using site-specific markers it is concluded that free quercetin and that coated on AgNPs bind at different sites. Significant structural changes in circular dichroism (CD) spectra of HSA were recorded with quercetin-coated AgNPs compared to free quercetin. These results were further substantiated by time-resolved fluorescence spectroscopy where fluorescence life time of the tryptophan residue in HSA–quercetin-coated AgNPs complex decreased to 3.63 ns from 4.22 ns in HSA–quercetin complex. Isothermal calorimetric studies reveal two binding modes for quercetin-coated AgNPs and also higher binding constants compared to free quercetin. These higher binding affinities are attributed to altered properties of quercetin when coated on AgNPs enabling it to reach the binding sites other than site II where free quercetin mainly binds.

Deciphering the biochemical and molecular mechanism underlying the in vitro and in vivo chemotherapeutic efficacy of ruthenium quercetin complex in colon cancer.

Flavonoids are the most investigated phytochemicals due to their pharmacological and therapeutic activities. Their ability to chelate with metal ions has resulted in the emergence of a new category of molecules with a broader spectrum of pharmacological activities. In this study, the ruthenium quercetin complex has been synthesized and anticancer activity has been evaluated on a well-defined model of DMH followed by DSS induced rat colon cancer and on human colon cancer cell line HT-29. The characterizations accomplished through UV-visible, NMR, IR, Mass spectra and XRD techniques, and antioxidant activity was assessed by DPPH, FRAP, and ABTS methods. In vitro study confirmed that the complex increased p53 expression, reduced VEGF and mTOR expression, apoptosis induction, and DNA fragmentation in the HT-29 cells. Acute and subacute toxicity study was also assessed and results from in vivo study revealed that complex was efficient to suppress ACF multiplicity and hyperplastic lesions and elevated the CAT, SOD, and glutathione levels. Furthermore, the complex was found to decrease cell proliferation and increased apoptotic events in tumor cells correlates upregulation of p53 and Bax and downregulation of Bcl2 expression. Our findings from the in vitro and in vivo study support the continued investigation of ruthenium quercetin complex possesses a potential chemotherapeutic activity against colon cancer and was efficient in reducing ACF multiplicity, hyperplastic lesions in the colon tissues of rats by inducing apoptosis.

Synthesis and Antioxidant Activity of Mixed Ligand Complex of Quercetin and Aspartic Acid with Cobalt(II)

Synthesis and Antioxidant Activity of Mixed Ligand Complex of Quercetin and Aspartic Acid with Cobalt(II)