Quercetin Complex Research Articles

Structurally characterized zinc complexes of flavonoids chrysin and quercetin with antioxidant potential

Chrysin and quercetin are two of the most prominent and bioactive flavonoids with a wide spectrum of beneficial properties, including antioxidant and radical scavenging activity. The complexation of these flavonoids with transition metal ions of biological interest can lead to the generation of novel metallodrugs with improved pharmacological and biochemical properties. Within this framework, the synthesis and detailed structural and physico-chemical characterization of two novel heteroleptic complex assemblies of Zn(II) with chrysin and quercetin and the ancillary aromatic chelator 2,2′-bipyridine is presented. The two complexes represent the only crystallographically characterized structures with Zn(II) as the central metal ion and chrysin or quercetin as the ligands. The new complexes were biologically evaluated in vitro for their antioxidant potential, both exhibiting strong radical scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl assay, and merit further investigation of their pharmacological profile.

Bangladeshi Wild Date Palm Fruits (Phoenix sylvestris): Promising Source of Anti-cancer Agents for Hepatocellular Carcinoma Treatment

Many natural products such as fruits and vegetables are promising amends as safe, effective and affordable approaches to control cancer development and progression, since they are inexpensive and available without any hazards. For instance, the aqueous extract of Ajwa dates (Phoenix dactilyfera) has been found to improve liver function through the restoration of anti-oxidant enzymes, liver enzymes, and cytokines balance and gene expression to normal levels. As the treatment and prognosis of Hepatocellular carcinoma, one of the leading causes of cancer associated deaths globally, has been found to be better if the liver function of the patient can be preserved, Ajwa date extract has been used together with the conventional therapeutics for the treatment of this disease. However, no study has been conducted so far on the anticancer activity of Bangladeshi wild date palm fruits (Phoenix sylvestris) despite the fact that it contains apigenin, quercetin, glucans, luteolin, and iron and vitamin complex. Therefore, in this review we discussed an idea that potential anticancer agents can be isolated from the extract of these fruits, which can eventually be used as an indigenous substance for the treatment of Hepatocellular carcinoma in our country and also the liver cancer inhibitory effects of the aqueous extract of these dates can be evaluated in rat model.
 Int. J. Appl. Sci. Biotechnol. Vol 9(1): 32-37

Enhancement of the antibiotic activity by quercetin against Staphylococcus aureus efflux pumps.

The objective of this work was to evaluate the inhibitory effect of quercetin on S. aureus Efflux Pumps. The MIC of Quercetin was evaluated through the broth microdilution method, as well as the Efflux Pump inhibition assay through the method of reducing the antibiotic minimum inhibitory concentration as well as that of ethidium bromide. The in silico approach through bioinformatics was performed to demonstrate the molecular mechanism of interaction of the substrate and the binding cavity. The Quercetin inhibition concentration was not clinically relevant. With respect to the reversal of bacterial resistance effect by efflux pump inhibition, this effect was observed with the strains carrying the TetK and NorA pumps. Regarding the interaction between the Quercetin complex and the NorA pump, the extra stability was provided by hydrogen bonds produced by the hydroxyl group.

Effects of serum matrix on molecular interactions between drugs and target proteins revealed by giant magneto-resistive bio-sensing techniques

We demonstrated that effects of serum matrix on molecular interactions between drugs and target proteins can be investigated in real time using magnetic bio-sensing techniques. A giant magneto-resistive (GMR) sensor was used on which target proteins were fixed and superparamagnetic nanoparticles (diameter: 50 nm) conjugated with drug were used in phosphate buffer, with and without serum. In this study, the following drug-protein pairs were investigated: quercetin and cAMP-dependent protein kinase A (PKA), Infliximab and tumor necrosis factor alpha (TNFα), and Bevacizumab and vascular endothelial growth factor (VEGF). For the quercetin and PKA pair, the time profile of the signal from the GMR sensor due to binding between quercetin and PKA clearly changed before and after the addition of serum. Moreover, it was revealed that not only the association process, but also the dissociation process was influenced by the addition of serum, suggesting that the quercetin and PKA complex may partially contain serum proteins, which affect the formation and stability of the complex. For antibody drugs, little effects of serum matrix were observed on both the association and dissociation processes. These clear differences may be attributed to the hydrophobic and electrostatic character of the drug molecule, target protein, and serum proteins. The real-time monitoring of molecular interactions in a biological matrix enabled by the GMR bio-sensing technique is a powerful tool to investigate such complicated molecular interactions. Understanding the molecular interactions that occur in a biological matrix is indispensable for determining the mechanism of action of the drugs and pharmacokinetics/pharmacodynamics inside the body. Additionally, this method can be applied for the analysis of the influence of any kind of third molecule that may have some interaction between two molecules, for example, an inhibitor drug against the interaction between two kinds of proteins.

Bioactive Zinc(II) complex incorporated PCL/gelatin electrospun nanofiber enhanced bone tissue regeneration

Bone tissue regeneration is augmented by biocompatible nanofiber scaffolds, that supports reliable and enhanced bone formation. Zinc is an essential mineral that is vital for routine skeletal growth and it emerges to be able to improve bone regeneration. Phytochemicals, particularly flavonoids have achieved prominent interest for their therapeutic ability, they have demonstrated promising effects on bone by encouraging osteoblastogenesis, which finally leads to bone formation. In this study, we have synthesized bioactive zinc(II) quercetin complex material and used for nanofibers scaffold fabrication to enhance bone tissue regeneration property. Two derivatives of zinc(II) quercetin complexes [(Zn(quercetin) (H2O)2) (Zn+Q), and Zn(quercetin)(phenanthroline) (Zn+Q(PHt)) have been synthesized and characterized using UV-Visible spectrophotometer and Fourier Transform-IR spectroscopy. The UV-Visible absorption and IR spectra prove the B-ring chelation of the flavonoid quercetin to zinc(II) rather C-ring chelation. The potential ability of the above synthesized metal complexes on osteogenesis and angiogenesis have been studied. Besides the bioactivity of the metal complexes, the control quercetin has also been examined. The chick embryo chorioallantoic membrane (CAM) assay demonstrated that the angiogenic parameters were increased by the (Zn+Q(PHt)) complex. Amongst, (Zn+Q(PHt)) complex showed significant activity and thereby this complex has been further examined for the bone tissue activity by incorporating the complex into a nanofiber through electrospinning method. At the molecular level, Runx2, mRNA and protein, ALP and type 1 collagen mRNAs, and osteoblast-specific microRNA, pre-mir-15b were examined using real time RT-PCR and Western blot assay. Histology studies showed that the (PCL/gelatin/Zn+Q(PHt)) was biocompatibility in-ovo. Overall, the present study showed that quercetin-zinc complex (Zn+Q(PHt)) incorporated into PCL/gelatin nanofiber can act as a pharmacological agent for treating bone associated defects and promote bone regeneration.

Antiparasitic Effects of Selected Isoflavones on Flatworms.

SummaryMedicinal plants have been successfully used in the ethno medicine for a wide range of diseases since ancient times. The research on natural products has allowed the discovery of biologically relevant compounds inspired by plant secondary metabolites, what contributed to the development of many chemotherapeutic drugs. Flavonoids represent a group of therapeutically very effective plant secondary metabolites and selected molecules were shown to exert also antiparasitic activity. This work summarizes the recent knowledge generated within past three decades about potential parasitocidal activities of several flavonoids with different chemical structures, particularly on medically important flatworms such as Schistosoma spp., Fasciola spp., Echinococcus spp., Raillietina spp., and model cestode Mesocestoides vogae. Here we focus on curcumin, genistein, quercetin and silymarin complex of flavonolignans. All of them possess a whole spectrum of biological activities on eukaryotic cells which have multi-therapeutic effects in various diseases. In vitro they can induce profound alterations in the tegumental architecture and its functions as well as their activity can significantly modulate or damage worm´s metabolism directly by interaction with enzymes or signaling molecules in dose-dependent manner. Moreover, they seem to differentially regulate the RNA activity in numbers of worm´s genes. This review suggests that examined flavonoids and their derivates are promising molecules for antiparasitic drug research. Due to lack of toxicity, isoflavons could be used directly for therapy, or as adjuvant therapy for diseases caused by medically important cestodes and trematodes.

A novel quercetin/β-cyclodextrin transdermal gel, combined or not with therapeutic ultrasound, reduces oxidative stress after skeletal muscle injury.

A gel containing the inclusion complex of quercetin and β-cyclodextrin was developed in order to verify its effects, isolated or using phonophoresis, on oxidative biomarkers after skeletal muscle injury. 30 male rats were divided into one of five groups: Control (CTRL), Muscle Injury (MI), Therapeutic Pulsed Ultrasound (TPU), Therapeutic Pulsed Ultrasound plus Quercetin (TPU plus gel-QUE) or Quercetin gel (QUE). Quercetin gel was complexed with β-Cyclodextrin (β-CD) using chromatography (HPLC). TPU and quercetin application occurred with 2, 12, 24, 48, 72, 96 hours intervals after injury. Gastrocnemius muscle was injured by mechanical trauma. Lipid peroxidation, superoxide dismutase activity, and catalase activity were assessed. The inclusion complex exhibited adequate entrapment efficiency, relative density and pH. The viscosity of the complex showed a non-Newtonian pseudoplastic behavior. Quercetin/β-cyclodextrin gel reduced lipid peroxidation, superoxide dismutase activity and catalase activity compared to muscle injury group. Similarly, phonophoresis and TPU also reduced the levels of these oxidative biomarkers. In conclusion, quercetin/β-cyclodextrin transdermal gel reduces oxidative stress biomarkers after skeletal muscle injury irrespective of using phonophoresis.

Iron (III)-Quercetin Complex: Synthesis, Physicochemical Characterization, and MRI Cell Tracking toward Potential Applications in Regenerative Medicine.

In cell therapy, contrast agents T1 and T2 are both needed for the labeling and tracking of transplanted stem cells over extended periods of time through magnetic resonance imaging (MRI). Importantly, the metal-quercetin complex via coordination chemistry has been studied extensively for biomedical applications, such as anticancer therapies and imaging probes. Herein, we report on the synthesis, characterization, and labeling of the iron (III)-quercetin complex, “IronQ,” in circulating proangiogenic cells (CACs) and also explore tracking via the use of a clinical 1.5 Tesla (T) MRI scanner. Moreover, IronQ had a paramagnetic T1 positive contrast agent property with a saturation magnetization of 0.155 emu/g at 1.0 T and longitudinal relaxivity (r1) values of 2.29 and 3.70 mM−1s−1 at 1.5 T for water and human plasma, respectively. Surprisingly, IronQ was able to promote CAC growth in conventional cell culture systems without the addition of specific growth factors. Increasing dosages of IronQ from 0 to 200 μg/mL led to higher CAC uptake, and maximum labeling time was achieved in 10 days. The accumulated IronQ in CACs was measured by two methodologies, an inductively coupled plasma optical emission spectrometry (ICP-EOS) and T1-weighted MRI. In our research, we confirmed that IronQ has excellent dual functions with the use of an imaging probe for MRI. IronQ can also act as a stimulating agent by favoring circulating proangiogenic cell differentiation. Optimistically, IronQ is considered beneficial for alternative labeling and in the tracking of circulation proangiogenic cells and/or other stem cells in applications of cell therapy through noninvasive magnetic resonance imaging in both preclinical and clinical settings.

Thermodynamic parameters and mitochondrial effects of supramolecular complexes of quercetin with β-cyclodextrins

The aim of the present study was to evaluate the thermodynamic parameters of the formation of supramolecular complexes of the flavonoid quercetin, a plant polyphenol with high therapeutic activity, and the molecular containers, β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD), as well as to assess the effects of quercetin and the quercetin - HPβСD complex on the functional activity of isolated rat liver mitochondria. The formation of the complex (stoichiometry 1:1) resulted in a marked elevation of quercetin water solubility: more than 5-fold in the case of 16 mM βCD (the association constant was equal to 300±45 М−1 as determined by the method of phase solubility diagram), and more than 50-fold in the case of 16 mM HPβCD (the association constant was equal to 3275±450 М−1), which reflects increased bioavailability of quercetin. In comparison, the association constant of the polyphenol sesamin - HPβСD complex formation (stoichiometry 1:1 and 1:2) was 2500 ± 350 М−1, and the solubility of sesamin in the complex increased more than 60-fold in the case of 10 mM HPβСD. The inclusion complex formation was spontaneous and exothermic, and both the enthalpic and entropic effects competed during complexation of polyphenol molecules with HPβCD, but the enthalpic factor was dominating in the bounding process in the case of quercetin and the entropic factor – in the case of sesamin. Quercetin and the quercetin - HPβCD complex considerably inhibited the respiratory activity of mitochondria, and uncoupled the oxidation and phosphorylation reactions, whereas quercetin alone, and not the complex, enhanced the mitochondria susceptibility to Ca2+-induced mitochondrial permeability transition (MPT). The complex quercetin - HPβCD (10–50 μM) was much more effective in preventing mitochondrial reduced glutathione depletion and α-ketoglutarate dehydrogenase impairment during mitochondria exposure to hypochlorous acid in comparison with the quercetin water solution due to enhanced availability of mitochondria matrix components to the antioxidant (quercetin). The decrease of quercetin lipophilicity after the complexation with HPβCD attenuated the effects on mitochondrial respiration and changed the direction of the effect on the MPT process owing to the quercetin redistribution between water and lipid phases.

Experimental and theoretical study on the coordination properties of quercetin towards aluminum(III), iron(III) and copper(II) in aqueous solution

In this work we have studied the complexation of quercetin (3,3′,4′,5,7-pentahydroxyflavone, H5Que) with aluminum(III), iron(III) and copper(II) at 37 °C and in aqueous solution (0.16 M NaCl). To evaluate the competition of the ligand for the metal cations and H+, the protonation constant of quercetin was also determined under the same experimental conditions. Speciation profiles obtained by potentiometric titrations and supported by UV–Vis data show that in aqueous solution a complexation occurs at 1:1 ligand-to-cations ratio for Al(III) and Cu(II), and at 1:1 and 1:2 ligand-to-Fe(III) ratio. The coordination sites of quercetin to the different metal ions were determined with the aid of 1H NMR and 13C NMR spectroscopy as well as by a computational approach. Synergies between experiment and computation show that aluminum and iron ions show no clear preference towards any of the complexation sites of quercetin, while for copper the 4,5 site (i.e., the 4‑carbonyl-5-hydroxyl site of the A and C rings of the ligand) could be excluded.

INVESTIGATION OF THE BIOLOGICAL ACTIVITY OF SEA BUCKTHORN MEAL FLAVONOIDS USING SPECIFIC BIOTEST SYSTEMS

The need to expand the raw material base for obtaining flavonoids is due to the wide spectrum of their biological activity. The purpose of this work is to study the biological activity of a complex of bioflavonoids, quercetin and rutin on specific enzyme biotest systems in vitro. The objects of the study were: a complex of bioflavonoids from fat-free sea buckthorn meal Hippophae rhamnoides L. and individual flavonoids rutin and quercetin isolated from it. The study was carried out by methods of detecting the biological activity of substances using specific enzyme biotest systems in vitro. It was revealed that rutin and a complex of bioflavonoids have antioxidant properties – the rate of glutathione reductase reaction increased by 64 and 51% of control, respectively, and catalase – by 15%. Quercetin exhibits antimicrobial activity and also reduces the rate of the enzymatic iNOS reaction by 24% of the control, which indicates the anti-inflammatory properties of this sample. Rutin and a complex of bioflavonoids from sea buckthorn meal increased the iNOS reaction rate by 14 and 28%, respectively, which indicates the immunostimulating properties of these samples. In the course of a microbiological study, it was found that all samples have weak bacteriostatic activity against gram-positive and gram-negative bacteria Staphylococcus aureus ATCC 6538 (209-P) and Pseudomonas aeruginosa ATCC 9027. Fungistatic activity was confirmed against the yeast-like fungi Candida albicans ATCC 10231 of quercetin and the complex. The results obtained make it possible to consider a complex of bioflavonoids, quercetin and rutin as promising active substances in antioxidant, antimicrobial, fungistatic and anti-inflammatory drugs.

Antidiabetic activity of cobalt–quercetin complex: A new potential candidate for diabetes treatment

The development of effective, available, safe, and less costly antidiabetic synthetic preparations based on natural products is of quite interest. To our knowledge, the flavonoid-based cobalt–quercetin complex was not tested before for its antidiabetic activities in vivo. Thus, our aim was to investigate the cobalt-quercetin complex’s (CQC) antidiabetic activities compared to the reference drug insulin in diabetic rats. Diabetes was prompted in male rats via one injection of streptozotocin (STZ, 50 mg/kg). Daily, diabetic animals were treated with either a dose of CQC or insulin for 15 days. Water and food intakes, bodyweight changes, total antioxidant capacity (TAC), hemoglobin A1C (HbA1C%), nitric oxide (NO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), albumin, lipid portrait, malondialdehyde (MDA), fasting blood glucose (FBG), superoxide dismutase (SOD), uric acid, and creatinine levels were assessed. Pancreas and liver tissues were histopathologically examined. STZ-induced insulin-dependent diabetes mellitus (IDDM) developed significant elevations in FBG, HbA1C, AST, ALT, NO, creatinine, urea, uric acid, and MDA levels, along with significant reductions in albumin, TAC, and SOD levels besides marked lipid profile disturbances and tissue histopathological changes. CQC treatment effectively reversed all the studied diabetes-induced changes via its strong antioxidant properties. Antidiabetic effects of CQC and insulin were comparable. Additional validation studies on the considerable CQC antidiabetic effects are needed.

The ratiometric detection and mechanism of three typical phosphonates by quercetin-based fluorescent probe with low detection limits

Phosphonates are efficient corrosion and scale inhibitors commonly used in industrial circulating water systems. However, conventional detection methods cannot accurately detect their concentration in some water bodies and sludge because of their low concentration. In this study, a ratiometric fluorescent probe was constructed based on quercetin (QC) and divalent zinc ion (Zn2+) to comparatively detect three typical phosphonates for the first time. Compared with the naked QC, Zn2+-quercetin complex (ZnQC) in the designed probe shows considerable differences in terms of luminescence properties and surface morphology. When the concentration of QC and Zn2+ were 10 mM and 50 μM, the detection limits for ATMP, HEDP, and DTPMPA were 0.223, 0.205 and 0.152 μM, respectively, which were lower than of the corresponding values obtained through the chromatography method and phosphomolybdenum blue spectrophotometry. Moreover, for the first time, the quantitative analysis of molecular surface, basin analysis, and atoms in molecules (AIM) analysis and non-covalent interaction analysis (NCI) in the Multiwfn program were employed to investigate the binding sites of QC with Zn2+. The electron excitation properties were further analyzed via theoretical calculations based on the dependent density functional theory (DFT) and time-dependent density functional theory (TDDFT). The detection mechanism can be ascribed to the static quenching considering the formation of non-fluorescent ground-state complexes. Additionally, the ratiometric probe demonstrated some features such as high sensitivity, selectivity, and a simpler operation which has been applied to detect practical water samples with satisfactory results.

Increasing the Resistance of the Body to Adverse Cytotoxic Effects of Amorphous Silicon Dioxide Nanoparticles

Introduction: Amorphous silicon dioxide nanoparticles of (SiNPs) are among the most common nanomaterials today. Besides, industrial aerosols formed by condensation and containing a significant proportion of SiNPs are spontaneously produced by a number of pyrometallurgical and welding processes. A significant number of individuals are therefore exposed to SiNPs in the occupational setting or polluted ambient air and while using this nanomaterial. The purpose of our experimental study was to develop a preventive method promoting the resistance of the organism to adverse cytotoxic effects of amorphous silicon dioxide nanoparticles. Materials and methods: White laboratory rats received a monthly course of a specially developed bioprophylactic complex (BPC) before a single intratracheal instillation of a SiNPs suspension at a concentration of 0.5 mg/mL. The suspension was obtained by laser ablation of thin sheet targets of the appropriate material of 99.99 % purity in sterile deionized water. The average diameter of SiNPs was 43 ± 11 nm. Cytological (the number of bronchoalveolar macrophages and neutrophils and their ratio) and cytochemical indices of the bronchoalveolar lavage (BAL) fluid (alkaline phosphatase, alanine aminotransferase, gamma-glutamyl transpeptidase, amylase, and lactate dehydrogenase) were evaluated at 24 hours after the injection. The bioprophylactic complex was administered to the animals with feed and drink and included monosodium glutamate, fish oil rich in omega-3 polyunsaturated fatty acids (PUFAs), iodine, and an antioxidant complex of selenium, quercetin (rutoside), and vitamins A, E, and C. Conclusions: Our findings show that changes in both cytological and biochemical BAL parameters proved a positive health effect of premedication that helped reduce cytotoxicity of SiNPs exposure.

2D DOSY NMR: A Valuable Tool to Confirm the Complexation in Drug Delivery Systems.

Many bioactive substances face the problem of limited bioavailability, mainly due to low aqueous solubility and poor metabolic stability. Their complexation with drug delivery systems offers a more optimum pharmacological profile. Some of these drug delivery systems that have promising potential form complexes with bioactive compounds such as cyclodextrins and calixarenes. The monitoring of the success and the type of the complexation are of great importance and two-dimensional diffusion-ordered NMR spectroscopy (2D DOSY) is a valuable tool for the studying of these complexes and described as "NMR chromatography." Herein we report the procedure for the complexation of the natural product quercetin in 2-hydroxypropyl-β-cyclodextrin and the anticancer drug temozolomide in p-sulfonatocalix[4]arene and the determination of the complexation with 2D DOSY spectroscopy.

THE ACTIVITY OF INTERMOLECULAR HYDROGEN COMPLEXES OF QUERCETIN WITH GLUCOSE IN REAC-TIONS WITH COTTON OIL PEROXY RADICALS

The presence of a strong synergistic effect of the binary quercetin–glucose composition in the reaction with peroxyl radicals generated during the auto- and initiated oxidation of cottonseed oil was established. The highest antiradical activity showed the synergistic compositions at a ratio of 60 : 40%. The established synergism refers to the type when products, formed during reaction, interacts with peroxy radicals more effectively than the original individual substances. Such products may be intermolecular hydrogen-bonded complexes of quercetin and glucose, the existence of such complexes confirmed by NMR spectroscopy. DFT method showed that the most stable is the donor H-complex, where quercetin acts as a hydrogen donor. A quantitative measure of the electron-donating properties of H complexes – the ionization potential – was calculated in the gas phase. The ionization potential of the donor complex is lower so its reducing ability in reaction with radicals is higher than that of the monomeric antioxidant.This can explain the presence of the maximum synergistic effect in the quercetin-glucose mixture at the ratio of 60 : 40%, when, probably, the proportion of donor H-complexes in the reaction mixture is maximum. Obtained results make it possible to carry out a targeted search for effective antioxidant synergistic flavonoid–carbohydrate compositions in plant extracts.

Stability, Hydrogen Bond Occupancy Analysis and Binding Free Energy Calculation from Flavonol Docked in DAPK1 Active Site Using Molecular Dynamic Simulation Approaches

Stability and hydrogen bond occupancy analysis of flavonol derivative docked in DAPK1 have been carried out using molecular dynamics simulation approach. Six flavonol derivatives were docked in DAPK1 as protein target, then continued with molecular dynamics simulation. NVT and NPT ensembles were used to equilibrate the system, followed by 20 ns sampling time for each system. Structural stability and hydrogen bond occupancy analyses were carried out at the NVT ensemble, while free binding energy analysis was done at NPT ensemble. From all compounds used in this work, compound B (5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one) has a similar interaction with reference ligands (quercetin, kaempferol, and fisetin), and the most stable complex system has the maximum RMSD around 2 Å. Compound C complex has -48.06 kJ/mol binding free energy score, and it was slightly different from quercetin, kaempferol, and fisetin complexes. Even though complex C has similar binding free energy with the reference compound, complex B shows more stable interactions due to their hydrogen bond and occupancy.

Preparation of β-CD-Quercetin Complex and its Effects on Ethanol- Damaged BRL-3A Hepatocytes.

To prepare the sustained-release complex, quercetin was incorporated with β- cyclodextrin (β-CD) and the effect of β-CD-quercetin complex on the growth of ethanol-injuried hepatocytes was studied. By using scanning electron microscopy, infrared spectroscopy, and release rate analysis, β- CD-quercetin complex was identified. The effect of different concentrations of β-CD-quercetin complex on the growth of ethanol-damaged hepatocytes at different time was observed by using MTT assay, and the cell quantity and morphology were observed by using hematoxylin-eosin staining. By using single-cell gel electrophoresis, the prevention of β-CD-quercetin complex from the DNA damage of ethanol-damaged BRL-3A cells was studied, and Olive tail moment was calculated. β-CD-quercetin complex as the sustained-release complex was successfully prepared. The ethanol induced damage of BRL-3A cells could be prevented by 20, 40 and 80 mg/L of quercetin complex, and the protection mechanism of hepatocyte was related to the antioxidation of DNA. Quercetin sustained-release complex could be prepared with β-CD, and it might be used to treat alcoholic liver disease.

Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy.

Cyclin-dependent kinase 6 (CDK6) is a potential drug target that plays an important role in the progression of different types of cancers. We performed in silico and in vitro screening of different natural compounds and found that quercetin has a high binding affinity for the CDK6 and inhibits its activity with an IC50 = 5.89 μM. Molecular docking and a 200 ns whole atom simulation of the CDK6-quercetin complex provide insights into the binding mechanism and stability of the complex. Binding parameters ascertained by fluorescence and isothermal titration calorimetry studies revealed a binding constant in the range of 107 M–1 of quercetin to the CDK6. Thermodynamic parameters associated with the formation of the CDK6–quercetin complex suggested an electrostatic interaction-driven process. The cell-based protein expression studies in the breast (MCF-7) and lung (A549) cancer cells revealed that the treatment of quercetin decreases the expression of CDK6. Quercetin also decreases the viability and colony formation potential of selected cancer cells. Moreover, quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression. Both in silico and in vitro studies highlight the significance of quercetin for the development of anticancer leads in terms of CDK6 inhibitors.

Mechanism of antioxidant properties of quercetin and quercetin-DNA complex.

Quercetin is the most abundant flavonoid with potent antioxidant activities. In the current research, the antioxidant properties of quercetin and quercetin-DNA complex were investigated theoretically and experimentally. Free radical scavenging experiments with thiobarbituric acid-reactive substances (TBARS) and 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) indicate that quercetin can protect DNA from free radical damage, and the antioxidant activity of the quercetin-DNA complex is stronger than quercetin. Deoxyriboseadenine-quercetin-dimethylphosphinic acid (DA-Q-P) model was extracted from molecular docking. The contributions of hydroxyl groups in quercetin and DA-Q-P model molecules to the antioxidant activity were investigated by computation of bond dissociation enthalpy (BDE) parameter and Fukui function, at B3LYP/6-311++G(2d,2p) level of theory. The results outlined that the hydroxyl groups from the B ring (3'-OH and 4'-OH) have a lower BDE compared with the ones from the A and C rings (3-OH, 5-OH, and 7-OH) and hence define antioxidant activity. The computational result based on Fukui function shows that the B ring is an electrophilic region. The interaction of antioxidant with DNA discovered at the molecular level could provide the structural basis of the antioxidant property of active ingredients in the flavonoids. It is of great significance to study the interaction mechanism between the small drug molecules with DNA at the molecular level.