Flavonols Quercetin Research Articles

Rutin as Neuroprotective Agent: From Bench to Bedside.

Flavonoids are major dietary constituents of plant-based food found ubiquitously in plant kingdom where they are usually present in substantial amounts. Rutin is a flavonol-type polyphenol which consists of the flavonol quercetin and the disaccharide rutinose. Rutin has been reported to exert diverse biological effects such as antitumor and antimicrobial mainly associated to its antioxidant and anti-inflammatory activities. Mental, neurological, and behavioural disorders are an important and growing cause of morbidity. Most of these disorders combine a high prevalence, early onset, progressive clinical course, and impairment of critical brain functions making them a major contributor to the global disease burden. In the present work, the biological in vitro and in vivo effects and the potential therapeutic applications of rutin in neurodegenerative processes are reviewed, as well as their bioavailability and pharmacokinetics, which are essential for a better understanding of its biological effectiveness. Moreover, the present review also provides an overview of the molecular mechanisms through which rutin is proposed to exert its neuroprotective effects.

Antioxidants, protein, oil content and fatty acids profiles of chia seeds (Salvia hispanica L.) genotype Tzotzol growing in three tropical ecosystems of Bolivia, Ecuador and Paraguay

Chia is a summer annual of the Lamiaceae. The objective of this study was to investigate the effect of growing location on the antioxidants content and composition in one genotype of chia, and the potential relationship with its major nutritional compounds, as protein, oil, and fatty acids. This study was carried out with black‑spotted chia seeds commercially grown in three different ecosystems, Tropical Rain Forest, Sub Humid Chaco, and Campo Cerrado, located in Ecuador, Bolivia and Paraguay, respectively. Flavonols quercetin, myrcetin, kaempherol, caffeic acid, chlorogenic acid, and SDG lignan compound presence was detected by chromatographic analysis. No significant (P<0.05) differences between seed origins= were found. Total oil content was significantly (P<0.05) higher in the seeds from Ecuador (34.2%) than all other locations, followed by the seeds from Bolivia (32.5%) which was significantly (P<0.05) higher compared to Paraguay (31.6%). The content of α‑linolenic fatty acid in seeds from Ecuador was significantly (P<0.05) higher compared to the seeds from all three locations. No significant correlation (P<0.05) between α -linolenic fatty acid and polyphenols content was detected. The results indicate that protein content, oil content and fatty acid profile characteristics of the chia are affected by the different ecological conditions of the tested ecosystems, which not affect the polyphenols content, and composition.

Transcriptome profiling reveals candidate flavonol-related genes of Tetrastigma hemsleyanum under cold stress

BackgroundTetrastigma hemsleyanum Diels et Gilg is a valuable medicinal herb, whose main bioactive constituents are flavonoids. Chilling sensitivity is the dominant environmental factor limiting growth and development of the plants. But the mechanisms of cold sensitivity in this plant are still unclear. Also, not enough information on genes involved in flavonoid biosynthesis in T. hemsleyanum is available to understand the mechanisms of its physiological and pharmaceutical effects.ResultsThe electrolyte leakage, POD activity, soluble protein, and MDA content showed a linear sustained increase under cold stress. The critical period of cold damage in T. hemsleyanum was from 12 h to 48 h. Expression profiles revealed 18,104 differentially expressed genes (DEGs) among these critical time points. Most of the cold regulated DEGs were early-response genes. A total of 114 unigenes were assigned to the flavonoid biosynthetic pathway. Fourteen genes most likely to encode flavonoid biosynthetic enzymes were identified. Flavonols of T. hemsleyanum might play a crucial role in combating cold stress. Genes encoding PAL, 4CL, CHS, ANR, FLS, and LAR were significantly up-regulated by cold stress, which could result in a significant increase in crucial flavonols (catechin, epicatechin, rutin, and quercetin) in T. hemsleyanum.ConclusionsOverall, our results show that the expression of genes related to flavonol biosynthesis as well as flavonol content increased in T. hemsleyanum under cold stress. These findings provide valuable information regarding the transcriptome changes in response to cold stress and give a clue for identifying candidate genes as promising targets that could be used for improving cold tolerance via molecular breeding. The study also provides candidate genes involved in flavonoid biosynthesis and may be useful for clarifying the biosynthetic pathway of flavonoids in T. hemsleyanum.

Dietary flavonoids: Nano delivery and nanoparticles for cancer therapy.

Application of nanotechnologies to cancer therapy might increase solubility and/or bioavailability of bioactive compounds of natural or synthetic origin and offers other potential benefits in cancer therapy, including selective targeting. In the present review we aim to evaluate in vivo studies on the anticancer activity of nanoparticles (NPs) obtained from food-derived flavonoids. From a systematic search a total of 60 studies were identified. Most of the studies involved the flavanol epigallocatechin-3-O-gallate and the flavonol quercetin, in both delivery and co-delivery (with anti-cancer drugs) systems. Moreover, some studies investigated the effects of other flavonoids, such as anthocyanins aglycones anthocyanidins, flavanones, flavones and isoflavonoids. NPs inhibited tumor growth in both xenograft and chemical-induced animal models of cancerogenesis. Encapsulation improved bioavailability and/or reduced toxicity of both flavonoids and/or co-delivered drugs, such as doxorubicin, docetaxel, paclitaxel, honokiol and vincristine. Moreover, flavonoids have been successfully applied in molecular targeted nanosystems. Selectivity for cancer cells involves pH- and/or reactive oxygen species-mediated mechanisms. Furthermore, flavonoids are good candidates as drug delivery for anticancer drugs in green synthesis systems. In conclusion, although human studies are needed, NPs obtained from food-derived flavonoids have promising anticancer effects in vivo.

Changes of the stability and bioactivity of quercetin and myricetin in BGC-823 cells in response to heat treatment and Fe2+/Cu2+ addition

Two flavonols quercetin and myricetin with heat treatment and Fe2+/Cu2+ addition were assessed for stability and bioactivity changes. Quercetin and myricetin at 37 °C showed higher degradation rate constants than those at 20 °C (0.133 − 1.025 vs. 0.299 − 1.803 h−1). Due to the chelation of flavonol and metals, Fe/Cu addition at the two temperatures (except Cu addition at 37 °C) mostly led to enhanced stability via decreasing the constant values to 0.064 − 0.675 h−1. Cell counting kit-8 assaying results showed that myricetin and quercetin heated at 37 °C and 100 °C received decreased growth inhibition in human gastric cancer BGC-823 cells, because they at 80 μmol/L showed decreased inhibition percentages (from 41.1 − 45.6 to 23.9 − 43.3%, cell treatment of 24 h; or from 46.6 − 51.9 to 28.8 − 46.5%, cell treatment of 48 h). The assaying results of Hoechst 33,258staining, DCFH-DA fluorescence probe, and flow cytometry also proved that the heated flavonols in the cells had less reactive oxygen species generation, lower DNA damage, and weakened apoptosis induction, compared with the unheated flavonols. Fe addition decreased these flavonol bioactivities in the cells because of decreased flavonol–Fe chelation and enhanced flavonol degradation; however, Cu addition induced oxidative stress and thus led to less bioactivity decrease than Fe addition. Correlation analysis results indicated that decreased reactive oxygen species generation of the two flavonols was correlated with decreased apoptosis induction (p < 0.05). Overall, these used treatments brought about stability and bioactivity changes for the two flavonols, suggesting reasonable consideration should be paid on processing conditions and some components of foods when studying food bioactivities.

Inhibition of CpLIP2 Lipase Hydrolytic Activity by Four Flavonols (Galangin, Kaempferol, Quercetin, Myricetin) Compared to Orlistat and Their Binding Mechanisms Studied by Quenching of Fluorescence.

The inhibition of recombinant CpLIP2 lipase/acyltransferase from Candida parapsiolosis was considered a key model for novel antifungal drug discovery and a potential therapeutic target for candidiasis. Lipases have identified recently as potent virulence factors in C. parapsilosis and some other yeasts. The inhibition effects of orlistat and four flavonols (galangin, kaempferol, quercetin and myricetin) characterized by an increasing degree of hydroxylation in B-ring, were investigated using ethyl oleate hydrolysis as the model reaction. Orlistat and kaempferol (14 µM) strongly inhibited CpLIP2 catalytic activity within 1 min of pre-incubation, by 90% and 80%, respectively. The relative potency of flavonols as inhibitors was: kaempferol > quercetin > myricetin > galangin. The results suggested that orlistat bound to the catalytic site while kaempferol interacted with W294 on the protein lid. A static mechanism of interactions between flavonols and CpLIP2 lipase was confirmed by fluorescence quenching analyses, indicating that the interactions were mainly driven by hydrophobic bonds and electrostatic forces. From the Lehrer equation, fractions of tryptophan accessibility to the quencher were evaluated, and a relationship with the calculated number of binding sites was suggested.

Isolation and characterization of six flavonoids from the leaves of Sterculia foetida Linn.

AbstractSix flavonoids, including one flavan‐3‐ol epicatechin (1), one flavone glycoside apigenin 7‐O‐β‐D‐glucopyranoside (2), three flavones namely dimethylchrysin (3), trimethylapigenin (4) and luteolin (5) and one flavonol quercetin (6) were isolated from the hexane and chloroform extracts of the leaves of Sterculia foetida Linn. collected in Binh Thuan Province by using various chromatographic methods. Their chemical structures were identified by comparing their spectroscopic data as well as physical properties with those in literature. Compounds 1‐4 were obtained for the first time in Sterculia genus.

The irrigation salinity and harvesting affect the growth, chemical profile and biological activities of Polygonum maritimum L.

Previously, our group identified the halophyte Polygonum maritimum L. (sea knotgrass) as a promising source of ingredients for the cosmetic, food, pharmaceutical and veterinarian industries. To further explore this species, and to guarantee the supply of biomass for commercial purposes, it is necessary to ensure its sustainable production while assuring the preservation of its chemical and biological properties. In this context, this work aimed to cultivate this species in greenhouse conditions and to determine the influence of specific agronomic conditions, namely irrigation salinity and harvest, on the plant’s growth performance and biological properties of obtained biomass. For that purpose, plants were grown in a greenhouse and irrigated with water with different salinities (0, 100, 200, 300 and 600 mM of sodium chloride - NaCl). After six weeks of irrigation, plants were cut 7 cm above soil level and submitted to an additional two harvests with a six-week interval. Plant growth performance was evaluated in terms of plant height, leaf number and surface area, moisture, and productivity. Acetone extracts were prepared from aboveground organs and evaluated for chemical composition (by spectrophotometric methods, and by ultra-high-resolution mass spectrometry - UHRMS), and for in vitro antioxidant properties [radical-scavenging activity (RSA) on DPPH and ABTS, ferric reducing antioxidant power (FRAP) and metal chelating activity on iron (ICA) and copper (CCA)]. Extracts were also appraised for in vitro anti-inflammatory activity on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Increased salinity and multiple harvests reduced plant growth and yields; the highest productivity was obtained in plants irrigated with freshwater at 2nd harvest (346 g/m2 of dried biomass). The extracts maintained the in vitro biological properties and interesting chemical profile, however, these depended on the irrigation salinity and harvest regime. The highest antioxidant activities were obtained in extracts from plants irrigated with freshwater at the 3rd harvest (DPPH: 96.2%; ABTS: 89.1%; CCA: 61.6%; FRAP: 136%). The extracts from biomass obtained in the 1st harvest of freshwater-irrigated plants, and from those treated with 100 and 200 mM of NaCl, had significant anti-inflammatory properties. The main compounds detected were mostly flavonols (myricetin and quercetin glycosides), which varied according to both irrigation salinity and harvest. Our results indicate that sea knotgrass can be cultivated in greenhouse conditions aiming industrial commercial applications, irrigated with freshwater or with irrigation solutions with moderate salinity. Moreover, produced biomass maintain the biological and chemical properties previously detected in plants collected from the wild.

The role of spin-phonon coupling in enhanced desorption kinetics of antioxidant flavonols from magnetic nanoparticles aggregates

Abstract An important criterion in the evaluation of drug delivery systems based on nanoparticles is the drug release kinetics. From numerous published works, it is obvious that the fraction of the released drug as a function of time shows qualitatively the same behaviour, even when the release is assisted by an external force. In this study a series of experiments has been performed on a system that can be considered as the simplest drug delivery system. It consists only of uncoated/unprotected superparamagnetic magnetite nanoparticles in the form of mesoporous aggregates and adsorbed flavonols (quercetin, myricetin, or myricitrin). The simultaneous utilization of external permanent and oscillating magnetic fields remarkably accelerated the flavonol release. There is no a specific pulling force that eventually causes the rupture of the bonds between the molecules and the particle surface, i.e. the detachment of an individual molecule is thermally activated. The adsorption of molecules onto nanoparticles follows almost without delay quick changes in the field-induced motion of the nanoparticles, and they are subject to more frequent collisions with the surrounding solvent molecules. The barrier fluctuations occur due to the magnetic field dependence of the nanoparticle phonon spectra, to which the adsorbed flavonol molecule vibrations are strongly coupled. The phonon frequencies and phonon damping of a ferromagnetic nanoparticle are actually affected by the magnetic field through the spin-phonon coupling. The rate of release (spontaneous or forced) is invariably a first-order process, which can be considered a basic property of a broad class of drug nanodelivery systems.

Theoretical study of the antioxidant capacity of the flavonoids present in the Annona muricata (Soursop) leaves.

A theoretical approach was used to evaluate the antioxidant capacity of 20 flavonoids reported in Annona muricata leaves. The theoretical study was at the GGA level using the wB97XD functional and the cc-pvtz basis set. The calculations were performed in gas phase and implicit solvent phase. The flavonol robinetin (03c) and the flavanol gallocatechin (01c) are species that exhibited the best antioxidant capacity in the HAT, SEPT, and SPLET mechanisms. On the other hand, in the SET I mechanism, flavonol quercetin (03b) was the best, and in the SET II mechanism, the most favored species is the flavanol catechin (01a). However, these species do not achieve to overcome the antioxidant capacity presented by the Trolox.

Hypolipidemic effect of ethanol extract from Mesona chinensis Benth. in high fat diet-induced obesity mice

Hypolipidemic effect of ethanol extract from Mesona chinensis Benth. in high fat diet-induced obesity mice

Extraction of the flavonol quercetin from onion waste by combined treatment with intense pulsed light and subcritical water extraction

The objective of this study was to develop a hurdle technology for maximizing the efficiency of extracting quercetin from onion waste skin by combining eco-friendly subcritical water extraction with physical pretreatment by intense pulsed light. The maximum concentration of quercetin was observed to be 17.32 ± 1.12 mg/g onion skin at the subcritical water extraction condition of 145 °C for 15 min with intense pulsed light at 1200 V for 60 s; the quercetin concentration was 15.19 ± 1.12 mg/g onion skin using subcritical water extraction alone at 145 °C for 15 min. The results might be attributable to intense pulsed light loosening the onion interstitial walls, which was detected by environmental scanning electron microscopy and fluorescence microscopy. This study has demonstrated that intense pulsed light is a promising pretreatment technology for enhancing the extraction of quercetin by subcritical water extraction. These results for re-utilization of products generated from onion waste would be helpful for developing sustainable, cost-effective, and efficient technologies for the reduction of food waste.

Correlations between urinary concentrations and dietary intakes of flavonols in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

In this study, we aimed to study the correlation between acute and habitual intakes of flavonols, their main food sources and their 24-h urinary concentrations in an European population. A 24-h dietary recall (24-HDR) and 24-h urine samples were collected on the same day from a convenience subsample of 475 men and women from four countries (France, Italy, Greece and Germany) of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A standardized 24-HDR software and a country/centre-specific validated dietary questionnaire (DQ) were used to collect acute and habitual dietary data, respectively. The intake of dietary flavonols was estimated using the Phenol-Explorer database. Urinary flavonols (quercetin, isorhamnetin, and kaempferol) were analysed using tandem mass spectrometry with a previous enzymatic hydrolysis. Weak partial Spearman correlations between both dietary acute and habitual intake and urinary concentrations of quercetin (both Rpartial ~ 0.3) and total flavonols (both Rpartial ~ 0.2) were observed. No significant correlations were found for kaempferol and isorhamentin. Regarding flavonol-rich foods, weak correlations were found between urinary concentrations of quercetin and total flavonols and the acute intake of onions and garlics, fruits, tea, and herbal tea (all Rpartial ~ 0.2). For habitual intake, statistically significant correlations were only found between urinary quercetin concentration and herbal tea (Rpartial = 0.345) and between urinary total flavonol concentration and tea, and herbal tea consumption (Rpartial ~ 0.2). Our results suggest that urinary quercetin level can be used as potential concentration biomarkers of both acute and habitual quercetin intake, while urinary concentrations of flavonols are unlikely to be useful biomarkers of individual flavonol-rich foods.

A Nutraceutical Strategy to Slowing Down the Progression of Cone Death in an Animal Model of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by progressive degeneration of the visual cells and abnormalities in retinal pigment epithelium, the vision is lost slowly, and the final outcome is total blindness. RP primarily affects rods, but cones can also be affected as a secondary effect. Photoreceptor cell death is usually triggered by apoptosis, however the molecular mechanisms linking the rod degeneration to the secondary cone death are poorly understood. Possible causes of the secondary cone death are oxidative stress and/ or the release of toxic factors from dying rods. The aim of this study is to analyze the effect of nutraceutical molecules with antioxidant properties, on the progression of the disease in an established animal model of RP, and rd10 mice. We show that chronic treatment per os with a flavanone (naringenin) or a flavonol (quercetin) present in citrus fruits, grapes and apples, preserves retinal morphology, and ameliorates functionality. These actions are associated with a significant reduction of stress-oxidative markers, such as the detoxifying enzymes Sod1 and Sod2. In addition, naringenin and quercetin treatment reduces the levels of acrolein staining associated with a reduction of ROS in the cellular environment. The study demonstrates the beneficial effects of naringenin and quercetin, two molecules that possess antioxidant properties, limiting neurodegeneration, and thus preventing cone damage.

Chemical Constituents of Phoebe poilanei and Their Cytotoxic Activity

Two new flavonol glycosides, rhamnocitrin 3- O-α-L-rhamnopyranosyl-(1→6)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside (1) and quercetin 3- O-6- Z- p-coumaroyl-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranoside (2), along with 3 flavonol glycosides, isoquercitrin (3), rutin (4), and quercetin 3- O-α-L-rhamnopyranosyl-(1→6)-β-D-galactopyranoside (5), and two known sesquiterpenes, alismol (6) and spathulenol (7), were isolated from the leaves of Phoebe poilanei Kosterm. Their chemical structures were elucidated by analyses of their high-resolution electrospray ionization mass spectral data and nuclear magnetic resonance spectral data and comparison with those reported in the literature. Two sesquiterpenes 6 and 7 were found to exhibit moderate cytotoxic activity with IC50 values ranging from 21.6 to 29.8 µM.

The granulopoietic cytokine granulocyte colony-stimulating factor (G-CSF) induces pain: analgesia by rutin.

Rutin is a glycone form of the flavonol quercetin and it reduces inflammatory pain in animal models. Therapy with granulocyte colony-stimulating factor (G-CSF) is known by the pain caused as its main side effect. The effect of rutin and its mechanisms of action were evaluated in a model of hyperalgesia induced by G-CSF in mice. The mechanical hyperalgesia induced by G-CSF was reduced by treatment with rutin in a dose-dependent manner. Treatment with both rutin + morphine or rutin + indomethacin, at doses that are ineffectual per se, significantly reduced the pain caused by G-CSF. The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG)-ATP-sensitive potassium channel (KATP) signaling pathway activation is one of the analgesic mechanisms of rutin. Rutin also reduced the pro-hyperalgesic and increased anti-hyperalgesic cytokine production induced by G-CSF. Furthermore, rutin inhibited the activation of the nuclear factor kappa-light-chain enhancer of activated B cells (NFκB), which might explain the inhibition of the cytokine production. Treatment with rutin upregulated the decreased mRNA expression of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) combined with enhancement of the mRNA expression of the Nrf2 downstream target heme oxygenase (HO-1). Intraperitoneal (i.p.) treatment with rutin did not alter the mobilization of neutrophils induced by G-CSF. The analgesia by rutin can be explained by: NO-cGMP-PKG-KATP channel signaling activation, inhibition of NFκB and triggering the Nrf2/HO-1 pathway. The present study demonstrates rutin as a promising pharmacological approach to treat the pain induced by G-CSF without impairing its primary therapeutic benefit of mobilizing hematopoietic progenitor cells into the blood.

Chemical and Sensorial Characterization of Tropical Syrah Wines Produced at Different Altitudes in Northeast of the Brazil

Over the years, viticulture has expanded to new regions outside the temperate zones, such as Northeast Brazil, India, Thailand, Myanmar, Vietnam, Bangladesh and Venezuela, characterized by the production of tropical wines. It is important for the productive sector to comprehend the effects of grapevine interaction with the characteristics of each new region on wines composition. In this study, the composition of wines of Syrah from two regions with different altitudes in Northeast Brazil were analyzed by different methodologies to characterize chemical compounds as sugar, acids, minerals, phenolics (anthocyanins, flavonols, stilbenes and condensed tannins) and the sensory profile. The wines of the Bahia region (1100 m of altitude) obtained high concentrations for chemical parameters related to color, monomeric anthocyanins, stilbenes and monomeric and oligomeric tannins. Wines of the low altitude region, Pernambuco (350 m of altitude) were characterized by higher concentrations of flavonols (kaempferol, isorhamnetin, quercetin and rutin) and polymerized tannins. The chemical composition of wines from the two studied regions was influenced by altitude. A trend towards higher concentrations in most for phenolic compounds analyzed was observed in wines from the higher altitude region during the two years of study. Regarding the sensory profile, fruity, floral, herbaceous and empyreumatic attributes aromatic obtained highest scores in wines of the 350 m altitude region, the other attributes were dependent on the year of harvest.

Thermodynamics of primary antioxidant action of flavonols in polar solvents

Abstract Very recently, a report on the antioxidant activity of flavonoids has appeared, where authors concluded that Hydrogen Atom Transfer mechanism represents the thermodynamically preferred mechanism in polar media (https://doi.org/10.1016/j.foodres.2018.11.018). Unfortunately, serious errors in the theoretical part of the paper led to incorrect conclusions. For six flavonols (galangin, kaempferol, quercetin, morin, myricetin, and fisetin), reaction enthalpies related to three mechanisms of the primary antioxidant action were computed. Based on the obtained results, the role of intramolecular hydrogen bonds (IHB) in the thermodynamics of the antioxidant effect is presented. Calculations and the role of solvation enthalpies of proton and electron in the determination of thermodynamically preferred mechanism is also briefly explained and discussed. The obtained results are in accordance with published works considering the Sequential Proton-Loss Electron-Transfer thermodynamically preferred reaction pathway.

A novel poly-oxygenated flavone glucoside from aerial parts of the Brazilian plant Neoglaziovia variegata (Bromeliaceae)

Neoglaziovia variegata is endemic to northeastern Brazil. The drought resistant plant produces edible fruits and is used as a fibre plant by rural communities in the Caatinga region where a variety of products are made from the white, soft and flexible fibres. Extracts of N. variegata have been reported to be of low toxicity and to exhibit antinociceptive effect, photoprotective potential, antioxidant effect, gastroprotective effects and antibacterial effect against both Gram-positive and Gram-negative bacteria, however, the chemical constituents of this species are mainly unknown. The novel poly-oxygenated flavone glucoside 5,6,7,4'-tetrahydroxy-3',5'-dimethoxy-flavone 7-O-β-glucopyranoside in addition to the rare poly-oxygenated flavone 5,4'-dihydroxy-6,7,3'-trimethoxyflavone 4'-O-β-glucopyranoside and the flavonol quercetin 3-O-(6''-rhamnopyranosyl-β-glucopyranoside) have been characterised from the leaves of N. variegata. 5,6,7,4'-tetrahydroxy-3',5'-dimethoxy-flavone, which comprises the core structure of the novel compound, is a new flavonoid aglycone in nature. The structure determinations were based on extensive use of 2D NMR spectroscopic techniques and high-resolution mass spectrometry. Both substances exhibited toxicity towards MOLM-13 acute myeloid leukaemia cells.

Graphene oxide as selective transporter of flavonols for physiological target DNA: A two-color fluorescence approach.

Our study determines the selectivity of graphene oxide (GO) to recognize its ligands (e.g. flavonoids) in facilitating the binding with their respective cellular targets. The polyhydroxy phenolic compounds, flavonoids, have a broad spectrum of therapeutic activities with high potency and low systemic toxicity. Despite the vast medicinal importance, their bioavailability is low. In this exploratory study, GO has been used as the transporter of three flavonols fisetin (3, 7, 3', 4'-OH flavone), quercetin (3, 5, 7, 3', 4'-OH flavone), and morin (3, 5, 7, 2', 4'-OH flavone) for the physiological target DNA. Calf thymus DNA is chosen as the model physiological target. Characterization of GO is performed using FTIR, Raman and dynamic light scattering (DLS) spectroscopy. The strong absorption peak at 1730 cm-1 indicated the presence of carbonyl groups (C=O) at the edges of GO. The presence of sp3 carbons due to oxidation of sp2 carbons in GO is further proved by Raman spectroscopy. DLS provided the average size of the GO particles to be ~9 μm. The dual luminescence behavior of the flavonols has been used in this study for the noninvasive sensing of the GO-flavonol and GO-flavonol-DNA interactions; as well as for the selectivity of GO for one flavonol over other in transferring the ligand to DNA. Furthermore, circular dichroism (CD) indicated that the optical activity of GO undergoes drastic change when conjugated with flavonols. Molecular modeling corroborated the findings from the binding studies. GO provides high promise as facilitators for drug delivery.