Search

Cell attachment to the extracellular matrix significantly impacts the integrity of tissues and human health. The integrin α5β1 is a heterodimer of α5 and β1 subunits and has been identified as a crucial modulator in several human carcinomas. Integrin α5β1 significantly regulates cell proliferation, angiogenesis, inflammation, tumor metastasis, and invasion. This regulatory role of integrin α5β1 in tumor metastasis makes it an appealing target for cancer therapy. The majority of the drugs targeting integrin α5β1 are limited only to clinical trials. In our study, we have performed 94287 compounds screening to determine potential drugs against α5β1 integrin. We have used ATN-161 as a reference and employed combined bioinformatic methodologies, including molecular modelling, virtual screening, MM-GBSA, cell-line cytotoxicity prediction, ADMET, Density Functional Theory (DFT), Non-covalent Interactions (NCI) and molecular simulation, to identify putative integrin α5β1 inhibitors. We found Taxifolin, PD133053, and Acebutolol that possess inhibitory activity against α5β1 integrin and could act as effective drug for the cancer treatment. Taxifolin, PD133053, and Acebutolol exhibited excellent binding to the druggable pocket of integrin α5β1, and also maintained a unique binding mechanism with extra hydrophobic contacts at molecular level. Overall, our study gives new pharmacological candidates that may act as a potential drug against integrin α5β1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Injectable pastes based on bioactive compounds and natural polymers are of interest in non-invasive bone surgeries. Several quantities of quercetin (100, 150, and 200 μM) were added to a sol-gel derived mesoporous bioactive glass. Injectable pastes based on quercetin-loaded bioactive glass, sodium alginate, and hyaluronic acid were prepared. Aggregated nanoparticles of bioactive glass and quercetin-loaded bioactive glass with mesoporous morphologies were confirmed by TEM and BET techniques. The quercetin release study was assessed in phosphate-buffered solution medium over 200 h and the obtained data were fitted by different eqs. A sustained release of quercetin was found, in which a better regression coefficient was achieved using Weibull equation. Human-derived mesenchymal stem cells were utilized to determine alkaline phosphatase activity and bone-related protein expression by western blotting and real-time PCR evaluations. Quercetin-loaded pastes increased the levels of alkaline phosphatase activity and the expression of Collagen-1, Osteopontin, Osteocalcin, and Runx2 proteins in a concentration-dependent manner. Due to the mesoporous architecture and high specific surface area of bioactive glass, the paste made of these particles and sodium alginate/hyaluronic acid macromolecules is appropriate matrix for quercetin release, resulting in promoted osteogenesis. The further in vivo studies can support the osteogenesis capacity of the quercetin-loaded paste., Competing Interests: Declaration of competing interest We wish to draw the attention of the Editor to the following facts which may be considered as potential conflicts of interest and to significant financial contributions to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Escherichia coli and Staphylococcus aureus are the most prevalent pathogenic bacteria, often resulting in the foodborne disease outbreaks through food spoilage and foodborne infections. To prevent and control food spoilage and foodborne infections induced by Escherichia coli and Staphylococcus aureus, the antibacterial hydrogels were fabricated using fibrinogen hydrolysate-carrageenan (AHs-C) and flavonoids (apigenin and quercetin), and the antibacterial effect of the composite hydrogels against Escherichia coli and Staphylococcus aureus was further investigated. The results of mechanical property exhibited that the composite hydrogels with 0.2 % of apigenin and quercetin (AHs-C-Ap/Que) showed the highest hardness and swelling property compared with the separate addition of apigenin or quercetin. Scanning electron microscopy and atomic force microscopy showed that the dense networks were formed in the hydrogels of AHs-C-Ap/Que., and the average roughness of AHs-C-Ap/Que. significantly increased to 30.70 nm compared with AHs-C. 1 H NMR and FTIR spectra demonstrated that apigenin and quercetin were bound to AHs-C by hydrogen bond, hydrophobic interaction and Schiff base, where the interactions between Ap/Que. and AHs-C was stronger compared with the separate addition of apigenin or quercetin. The hydrogels of AHs-C-Ap/Que. showed the highest antibacterial capacity and antibacterial adhesion against Escherichia coli and Staphylococcus aureus. The antibacterial adhesion assay showed that 99 % removal ratios for E. coli and S. aureus were observed in AHs-C-Ap/Que. hydrogels, which showed a great potential to prevent food spoilage and foodborne infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, in order to solve the application problems of poor water solubility and low bioavailability of quercetin, we prepared a nano-delivery system with core-shell structure by anti-solvent method, including a hydrophilic shell composed of tea saponin and a hydrophobic core composed of Zein, which was used to improve the delivery efficiency and biological activity of quercetin. Through the optimal experiments, the loading rate and encapsulation rate of nanoparticles reached 89.41 % and 7.94 % respectively. And the water solubility of quercetin is improved by 30.16 times. At the same time, the quercetin acted with Zein through non-covalent interaction and destroyed its spatial network through structural characterization, while tea saponin covered the surface of Zein through electrostatic interaction, making it change into amorphous state. In addition, the addition of tea saponin makes the nanoparticles remain stable under the changes of external environment. During simulating gastrointestinal digestion procedure, ZQTNPs has higher release rate and bioavailability than free quercetin. Importantly, ZQTNPs can overcome the limitations of a single substance through synergy. These results will promote the innovative development of quercetin precision nutrition delivery system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The basis of most neurological syndromes is the accumulation of free radical molecules. Quercetin is a polyphenolic bioflavonoid molecule and it has a very strong antioxidant effect by maintaining oxidative balance. There are many difficulties in the clinical use of quercetin due to its hydrophobic structure, low solubility, instability, poor oral bioavailability, and limited tissue-barrier penetration. Its synergistic use in complex with gold nanoparticles (AuNPs) could overcome these problems. AuNPs have recently emerged as an attractive candidate for delivery applications of various biomolecules and drugs. The aim of this study was to synthesize two different sized gold nanoparticles (AuNP 20 and AuNP 50 ) modified with polyethyleneimine (PEI) and quercetin, evaluate their potential neuroprotective effects on the in vitro oxidative stress model using DRG primary sensory neurons. It was shown that the antioxidant and anti-apoptotic ability of the bioflavonoid was preserved after exposure to the designed quercetin modified AuNPs. The PEI surface coating increased the stability and biocompatibility of the AuNPs in both sizes. It also potentially enables additional surface functionalization. This study indicates that designed nanoparticles (AuNP-Q-PEI) with different sizes could be a useful potential platform for the treatment of neurodegenerative syndromes or cancer diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Three nanoparticles were fabricated for the co-delivery of quercetin and resveratrol. Nanoparticles consisted of a zein and carboxymethyl cellulose assembled using antisolvent precipitation/layer-by-layer deposition method. Nanoparticles contained quercetin in the core and resveratrol in the shell, resveratrol in the core and quercetin in the shell or both quercetin and resveratrol in the core. The particle sizes of nanoparticles were 280.4, 214.8, and 181.8 nm, respectively. Zeta-potential was about -50 mV and PDI was about 0.3. The different positions of polyphenol distribution nanoparticles could reduce the competition between the two polyphenols, the encapsulation rate, loading rate and storage stability reached up to 91.7 %, 5.37 % and 97.1 %, respectively. FT-IR showed that hydrophobic and electrostatic interactions were the main driving forces of nanoparticle assembly. XRD showed that two polyphenols were successfully encapsulated in nanoparticles. TGA showed that distributing the nanoparticles in different layers would enhance thermal stability. TEM and SEM showed that polysaccharides attached to the surface of nanoparticles formed a core-shell structure with uniform particle size. All three nanoparticles could release two polyphenols slowly in simulated gastrointestinal digestion, Korsmeyer-Peppas was the most suitable kinetic release model. Therefore, biopolymer-based nanocarriers can be created to enhance the loading, stability, and bioaccessibility of co-encapsulated nutraceuticals., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel thermoreversible emulsion gel was successfully prepared with citrate agar (CA) as the sole emulsifier. Compared with native agar gel emulsion, CA gel emulsion (CAGE) formed a stable emulsion gel when the CA concentration was increased to 1.25 % (w/w). Results of time-temperature scanning experiments showed that the emulsion gel rapidly transformed into liquid emulsion when heated to 40-50 °C and then solidified into emulsion gel after cooling to the critical temperature of solidification. The emulsion gel had stable sol-gel transformation ability after seven cycles repeated heating-cooling treatment (HCT) at 85 °C and 4 °C. However, the stability of emulsion gels gradually decreased because of the large-droplet formation during heating, which affected the CA molecular-reconfiguration network structure in cooling. The conjunction analysis of microstructure and properties of the emulsion gel indicated that its stability depended primarily on the spatial repulsion and electrostatic repulsion provided by CA gel, and the main factor driving thermal reversibility was the temperature-responsive gelation performance of CA. The retention of quercetin was >90.23 % after seven HCTs because CAGEG enhanced the homogeneity and stability of the droplets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quercetin possesses multiple biological activities. To achieve efficient colon-specific release of quercetin, new composite nanofibers were developed by coating pH-responsive shellac on hydrophilic gelatin through coaxial electrospinning. These composite nanofibers contained bead-like structures. The encapsulation efficiency (87.6-98.5 %) and loading capacity (1.4-4.1 %) varied with increasing the initial quercetin addition amount (2.5-7.5 %). FTIR, XRD, and TGA results showed that the quercetin was successfully encapsulated in composite nanofibers in an amorphous state, with interactions occurring among quercetin, gelatin, and shellac. Composite nanofibers had pH-responsive surface wettability due to the shellac coating. In vitro digestion experiments showed that these composite nanofibers were highly stable in the upper gastrointestinal tract, with quercetin release ranging from 4.75 % to 12.54 %. In vivo organ distribution and pharmacokinetic studies demonstrated that quercetin could be sustainably released in the colon after oral administration of composite nanofibers. Besides, the enhanced anticancer activity of composite nanofibers was confirmed against HCT-116 cells by analyzing their effect on cell viability, cell cycle, and apoptosis. Overall, these novel composite nanofibers could deliver efficiently quercetin to the colon and achieve its sustained release, thus potential to regulate colon health. This system is also helpful in delivering other bioactives to the colon and exerting their functional effects., Competing Interests: Declaration of competing interest There have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The primary challenge in percutaneous coronary interventions for vascular restenosis is the occurrence of restenosis, which is defined by the excessive proliferation of neointimal tissue. Herein, our research team suggests that exosomes obtained from PSC, when paired with quercetin (Q@PSC-E), successfully reduce neointimal hyperplasia in a Sprague-Dawley rat model. Furthermore, the physical properties of the synthesized Q@PSC-E were examined using UV-vis, DLS, and FT-IR characterization techniques. The rats were subjected to balloon injury (BI) utilizing a 2-Fr Fogarty arterial embolectomy balloon catheter. Intimal hyperplasia and the degree of VSMC proliferation were evaluated using histological analysis in the rat groups that received a dosage of Q@PSC-E at 30 mg/kg/d. Significantly, Q@PSC-E inhibited cell proliferation through a pathway that does not include lipoxygenase, as demonstrated by [ 3 H] thymidine incorporation, MTT, and flow cytometry studies. Additionally, the data indicate that Q@PSC-E hinders cell proliferation by targeting particular events that promote cell growth, including the activation of Akt and NF-κB, disruption of cell-cycle progression and also obstructs the ERK signaling pathway., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inhibition of pancreatic lipase (PL) is a strategy to prevent obesity. The inhibitory effects of Flos Sophorae Immaturus (FSI) extract and its main flavonoid components, rutin and quercetin, on PL were investigated. The contents of rutin and quercetin in FSI extract were 44.10 ± 1.33 % and 6.07 ± 1.62 %, respectively. The IC 50 values of FSI extract, rutin and quercetin on PL were 322, 258 and 71 μg/mL, respectively. Rutin and quercetin inhibited PL in a reversible and noncompetitive manner. The combination of rutin and quercetin exhibited synergistic inhibitory effects at low concentration. The binding of rutin/quercetin with PL caused the fluorescence quenching of protein. Fluorescence titration showed the binding affinity of quercetin with PL protein was stronger than that of rutin. Circular dichroism analysis showed the binding changed the secondary structure of PL with an increase in random coil and a decrease in α-Helix and β-Sheet. Molecular docking revealed that rutin and quercetin could interact with the amino acid residues around the catalytic site through multiple secondary interactions. In vivo studies showed that FSI extract can reduce fat absorption and promote fecal fat excretion through inhibition of PL activity, and the effects were mainly due to rutin and quercetin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phytochemicals, plant-derived compounds, are the major components of traditional medicinal plants. Some phytochemicals have restricted applications, due to low bioavailability and less efficacy. However, their medicinal properties can be enhanced by converting them into value-added products for different bioactivities like anti-oxidant, neuroprotective, anti-obesity, anti-neuroinflammatory, anti-microbial, anti-cancer and anti-inflammatory. Microbial transformation is one such process that is generally more specific and makes it possible to modify a compound without making any unwanted alterations in the molecule. This has led to the efficient production of value-added products with important pharmacological properties and the discovery of new active compounds. The present review assimilates the existing knowledge of the microbial transformation of some phytochemicals like eugenol, curcumin, ursolic acid, cinnamaldehyde, piperine, β-carotene, β-sitosterol, and quercetin to value-added products for their application in food, fragrances, and pharmaceutical industries., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Quercetin (QC) is known as a typical antioxidant as a bioflavonoid, and its quick, sensitive, and specific detection is crucial for assessing food products. In this study, for the purpose of luminescence-based sensing of QC, bright bluish-green emissive quantum dots of N-doped MXene-based titanium carbide (Ti 3 C 2 ) were fabricated. Recently, MXene quantum dots (MX-QDs), the rapidly emerging zero-dimensional nanomaterials made from two-dimensional transition metal carbides, have attracted much interest due to their unique physical and chemical features. These include the extremely large surface-to-volume ratio, biocompatibility, luminescence tunability, and hybridization capability while retaining properties of their two-dimensional counterpart including good conductivity and charge transferability., Results: The fabricated Ti 3 C 2 MX-QDs had a quantum yield of 8.13 % at the emission wavelength of λ em  = 465 nm and displayed excellent photostability with great colloidal stability. It was found that introducing QC to near Ti 3 C 2 MX-QDs reduced their fluorescence signals due to quenching effects. These quenching effects that occurred in a very broad linear range of QC (25-600 nM) enabled QC to be sensed quantitatively with the limit of detection of QC (1.35 nM), being the lowest ever reported to date. The quenching phenomena that caused such excellent sensitivity could be accounted for by combined effects of static quenching/radiation-free complex formation and inner filter effects (IFE) of Ti 3 C 2 MX-QDs with QC., Significance: In addition, the quenching-based detection demonstrated excellent specificity against structurally relevant interferants. Therefore, the presented sensing strategies with Ti 3 C 2 MX-QDs-based fluorescence quenching can be one of the strongest candidates as a reliable and cost-effective solution to highly sensitive quantification of QC in food samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

PIM-1 kinase belongs to the Ser/Thr kinases family, an attractive therapeutic target for prostate cancer. Here, we screened about 100 natural substances to find potential PIM-1 inhibitors. Two natural compounds, Naringenin and Quercetin, were finally selected based on their PIM-1 inhibitory potential and binding affinities. The docking score of Naringenin and Quercetin with PIM-1 is -8.4 and - 8.1 kcal/mol, respectively. Fluorescence binding studies revealed a strong affinity (Ka values, 3.1 × 10 4  M -1 and 4.6 × 10 7  M -1 for Naringenin and Quercetin, respectively) with excellent IC 50 values for Naringenin and Quercetin (28.6 μM and 34.9 μM, respectively). Both compounds inhibited the growth of prostate cancer cells (LNCaP) in a dose-dependent manner, with the IC 50 value of Naringenin at 17.5 μM and Quercetin at 8.88 μM. To obtain deeper insights into the PIM-1 inhibitory effect of Naringenin and Quercetin, we performed extensive molecular dynamics simulation studies, which provided insights into the binding mechanisms of PIM-1 inhibitors. Finally, Naringenin and Quercetin were suggested to serve as potent PIM-1 inhibitors, offering targeted treatments of prostate cancer. In addition, our findings may help to design novel Naringenin and Quercetin derivatives that could be effective in therapeutic targeting of prostate cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

It is still difficult for a single antibacterial modality to realize satisfactory management of bacterial breeding in food preservation. To solve this problem, we developed a photothermal-derived dual-mode synergistic bactericidal konjac glucomannan (KGM)/polycaprolactone (PCL) bilayer film incorporated with quercetin-loaded melanin-like nanoparticles (Q@MNPs). The results showed that the mechanical properties (TS: 29.8 MPa, EAB: 43.1 %), UV shielding properties, and water resistance (WCA: 124.1°, WVP: 3.92 g mm/m 2  day kPa) of KGM-Q@MNPs/PCL bilayer films were significantly improved. More importantly, KGM-Q@MNPs/PCL bilayer film presented outstanding photothermal inversion and controlled release behavior of Q triggered by near infrared (NIR) radiation, thus contributing to excellent dual-mode synergistic antibacterial properties against E. coli and S. aureus. Meanwhile, the KGM-Q@MNPs/PCL bilayer film possessed good biocompatibility and low toxicity. As a proof-of-concept application, we further verified the significant value of film for the preservation of cherry tomatoes. Since KGM-Q@MNPs/PCL bilayer film showed excellent biodegradability, this work will aid the development of sustainable antibacterial food packaging materials., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anti-osteoporotic agents are clinically employed to improve bone health and prevent osteoporotic fractures. In the current study, we investigated the potential of chitosan-quercetin bio-conjugate as an anti-osteoporotic agent. The conjugate was prepared and characterized by FTIR and found notable interactions between chitosan and quercetin. Treating mouse MSCs with the bioconjugate in osteogenic conditions for a week led to elevated expression of differentiation markers Runx2, ALP, and Col-I, as determined by real-time PCR analysis. Evaluation at the cellular level using alizarin red staining demonstrated enhanced calcium deposition in MSCs following treatment with the bioconjugate. Likewise, ELISA analysis showed significantly elevated levels of secretory osteocalcin and osteonectin in groups treated with the conjugate. To broaden our comprehension, we utilized a zebrafish-based in vivo model of dexamethasone-induced osteoporosis to investigate bone regeneration. Toxicity profiling with zebrafish larvae confirmed the bio-conjugate's compatibility at a concentration of 25 μg/ml, underscoring the significance of finding the right dosage. Furthermore, in zebrafish models of osteoporosis, the bio-conjugate demonstrated significant potential for bone regeneration, as indicated by improved bone calcification, callus formation, and overall bone healing in a tail fin fracture model. Additionally, the study revealed that the bio-conjugate inhibited osteoclastic activity, leading to reduced TRAP activity and hydroxyproline release, suggesting its effectiveness in mitigating bone resorption. In conclusion, our research provides compelling evidence for the osteogenic capabilities of the chitosan-quercetin bio-conjugate, highlighting its promising applications in regenerative medicine and the treatment of conditions like osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polyphenol has the considerable effects for inhibition of digestive enzymes, however, inhibition mechanism of molecular size-dependent polyphenols on enzyme activity is still lacking. Herein, inhibition effect and binding interactions of three different structural polyphenols (catechol, quercetin and hesperidin) on α-amylase were studied. Inhibition assays proved that polyphenols significantly inhibited α-amylase and their effects were increased with their molecular sizes. Hesperidin showed the highest inhibition ability of α-amylase, which was determined as IC 50  = 0.43 mg/mL. Fluorescence and FT-IR spectroscopy proved that inter-molecular interactions between polyphenols and α-amylase occurred through non-covalent bonds. Besides, the secondary structure of α-amylase was obviously changed after binding with polyphenols. Inter-molecular interactions were investigated using solid-state NMR and molecular docking. Findings proved that hydrogen bonds and π-π stacking interactions were the mainly inter-molecular interactions. We hope this contribution could provide a theoretical basis for developing some digestive enzyme inhibitors from natural polyphenols., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we have co-loadedatorvastatin (ATR) and quercetin (QCT) in a nonionic microemulsion. After developing a derivative ratio spectrophotometric technique for simultaneous analysis of ATR and QCT, pseudoternary phase diagram was constructed utilizing1:4 d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and ethanol as surfactant and cosurfactant, respectively. Oleic acid was used as oil phase. Structural characterization of the formulation was carried out along a water dilution line created in monophasic region. Characterizations at these dilution points were performed using dynamic light scattering and polarized light microscopy. The average hydrodynamic size of the optimized formulation was found to be 18.9 nm and it did not change upon loading of ATR and QCT. In vitro release was assessed for the formulations loaded with different ratios of ATR and QCT, and the data were fitted to different mathematical models. Interestingly, we noticed differences in release kinetics during changes in dose ratios, particularly for QCT. Higuchi kinetics, observed at equal dose, shifted to Korsmeyer-Peppas model at higher QCT-ATR ratio (2:1 and 4:1). This difference is attributable to the ability of QCT molecules of overwhelming the interface at higher concentrations. Altogether, our observations highlight that the ratio of payloads should be selected carefully in order to avoid unpredictable release patterns., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, the stabilization mechanism and digestion behavior of Pickering emulsion prepared by a combination of chitosan (CS) and TEMPO-oxidized hyaluronic acid (HA) were investigated. Conductometric titration was used to determine the degree of oxidation and carboxylate content of TEMPO-oxidized HA. The results showed that the degree of oxidation increased proportionally with increasing oxidation time, and the electrostatic and hydrogen bonding interactions with CS were significantly enhanced. The results of FTIR and TEM showed the formation of CS/oxidized HA nanoparticles (CS/oxidized-HANPs). In addition, the contact angle of CS/oxidized-HANPs is closed to 77°, thereby providing higher desorption energy at the interface. Rheological results showed that the Pickering emulsion exhibited a gel-like network structure and higher viscosity. In vitro digestion results suggested that the quercetin (Que) bioaccessibility of the CS/oxidation HANps-stabilized Pickering emulsion with an oxidation time of 20 min was better than that of the conventional emulsion prepared with CS alone. The research is expected to develop novel polysaccharide-based Pickering emulsion delivery systems for functional compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polyphenols, polysaccharides, and proteins are essential nutrients and functional substances present in food, and when present together these components often interact with each other to influence their structure and function. Proteins and polysaccharides are also excellent carrier materials for polyphenols. In this context, this study investigated the non-covalent interactions between taxifolin (TAX), Lentinus edodes mycelia polysaccharide (LMP), and β-casein (β-CN). β-CN and LMP spontaneously formed nanocomplexes by hydrogen bonds and van der Waals forces. The quenching constant and binding constant were (1.94 ± 0.02) × 10 13  L mol -1  s -1 and (3.22 ± 0.17) × 10 5  L mol -1 at 298 K, respectively. The altered conformation of β-CN, resulting from the binding to LMP, affected the interaction with TAX. LMP significantly enhanced the binding affinity of TAX and β-CN, but did not change the static quenching binding mode. The binding constant for β-CN-TAX was (3.96 ± 0.09) × 10 13  L mol -1 , and that for the interaction between TAX and β-CN-LMP was (32.06 ± 0.05) × 10 13  L mol -1 . In summary, β-CN-LMP nanocomplexes have great potential as a nanocarrier for polyphenols, and this study provides a theoretical foundation for the rational design of non-covalent complexes involving LMP and β-CN, both in binary and ternary configurations., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 μg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t 1/2α : 5.7 ± 4.3 min) and a slower elimination phase (t 1/2β : 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Burn wounds (BWs) cause impairment of native skin tissue and may cause significant microbial infections that demand immediate care. Curcumin (Cur) and quercetin (Que) exhibit antimicrobial, hemocompatibility, ROS-scavenging, and anti-inflammatory properties. However, its instability, water insolubility, and low biological fluid absorption render it challenging to sustain local Cur and Que doses at the wound site. Therefore, to combat these limitations, we employed blow-spinning and freeze-drying to develop a multi-layered, Cur/Que-loaded gelatin/chitosan/PCL (GCP-Q/C) nanofibroporous (NFP) matrix. Morphological analysis of the NFP-matrix using SEM revealed a well-formed multi-layered structure. The FTIR and XRD plots demonstrated dual-bioactive incorporation and scaffold polymer interaction. Additionally, the GCP-Q/C matrix displayed high porosity (82.7 ± 2.07 %), adequate pore size (∼121 μm), enhanced water-uptake ability (∼675 % within 24 h), and satisfactory biodegradation. The scaffolds with bioactives had a long-term release, increased antioxidant activity, and were more effective against gram-positive (S. aureus) and gram-negative (E. coli) bacteria than the unloaded scaffolds. The in vitro findings of GCP-Q/C scaffolds showed promoted L929 cell growth and hemocompatibility. Additionally, an in vivo full-thickness BW investigation found that an implanted GCP-Q/C matrix stimulates rapid recuperation and tissue regeneration. In accordance with the findings, the Gel/Ch/PCL-Que/Cur NFP-matrix could represent an effective wound-healing dressing for BWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multifunctional agents with therapeutic and diagnostic capabilities are imperative to the prevention of Alzheimer's disease (AD), which is considered due to abnormal aggregation and deposition of β-amyloid protein (Aβ) as well as oxidative stress. Herein, quercetin (Que)- and p-phenylenediamine (p-PD)-derived red emission carbon dots (CDs) synthesized via a one-step hydrothermal method were designed as a novel theranostic nano-agent for the multi-target treatment of AD. R-CD-75 with an optimized composition exhibited significant inhibition of Aβ aggregation and rapid depolymerization of mature Aβ fibrils (<4 h) at micromolar concentrations (2 and 5 μg/mL, respectively). Moreover, R-CD-75 potently scavenged reactive oxygen species and showed turned-on red fluorescence imaging of Aβ plaques both in vitro and in vivo. In vitro assays proved that R-CD-75 significantly mitigated the Aβ-induced cytotoxicity and enhanced the cultured cell viability from 74.9 % to 98.0 %, while in vivo studies demonstrated that R-CD-75 prolonged the lifespan of AD nematodes by over 50 % (from 13 to 20 d). Compared to the precursors Que and p-PD, R-CD-75 inherited some of their structures and functional groups, such as aromatic structures, phenolic hydroxyl and amino groups, which were considered to interact with Aβ species through hydrogen bonding, electrostatic interactions, hydrophobic interactions, and π-π stacking, thus contributing to its effectiveness in its theranostic functions. This research has opened a new avenue to the development of potent theranostic agents by designing novel carbon dots., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

We prepared a naturally occurring flavanoid namely quercetin from tea leaves and analyzed by Absorption, Emission, FT-IR, 1 H, 13 C nmr spectra and ESI-MS analysis. The inclusion behavior of quercetin in cyclodextrins like α-, β-, γ-, per-6-ABCD and mono-6-ABCD cavities were supported such as UV-vis., Emission, FT-IR and ICD spectra and energy minimization studies. From the absorption and emission results, the type of complexes formed were found to depend on stoichiometry of Host:Guest. FT-IR data of CD complexes of quercetin supported inclusion complex formation of the substrate with α-, β- and γ-CDs. The inclusion of host-guest complexation of quercetin with α-, β-, γ-CDs, per-6-ABCD and mono-6-ABCDs provides very valuable information about the CD:quercetin complexes, the study also shows that β-CD complexation improves water solubility, chemical stability and bioavailability of quercetin. Besides, phase solubility studies also supported the formation of 1:1 drug-CD soluble complexes. All these spectral results provide insight into the binding behavior of substrate into CD cavity in the order per-6-ABCD > Mono-6-ABCD > γ-CD > β-CD > α-CD. The proposed model also finds strong support from the fact with excess CD this exciton coupling disappears indicates the formation of only 1:1 complex., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, the curdlan-polyphenol complexes were constructed by a pH-driven method. The interaction between curdlan and various hydrophobic polyphenols (curcumin, quercetin, and chlorogenic acid) was investigated. Curdlan could self-assemble into particles for loading polyphenols through hydrogen bonding and hydrophobic interactions. The three polyphenols were embedded in curdlan in an amorphous state. The curdlan-curcumin complex showed the lowest viscoelasticity but exhibited the highest curcumin loading ability (34.04 ± 1.73 mg/g). However, the curdlan-chlorogenic acid complex emerged the opposite trend, indicating that the loading capacity was associated with the hydrophobicity of polyphenols. The antioxidant activity of curdlan significantly increased after combining with polyphenols, which could be maintained during in vitro simulated gastrointestinal digestion. In particular, the curdlan-quercetin complex exhibited the highest antioxidant activity and short-chain fatty acid concentration, which could influence gut microbiota composition by promoting the proliferation of Prevotella and inhibiting the growth of Escherichia&#95;Shigella. In conclusion, the curdlan-polyphenol complexes prepared by an alcohol-free pH-driven method could effectively enhance the gastrointestinal stability of polyphenols as well as increase the antioxidant and prebiotic activities of curdlan, which could be applied as a functional ingredient to improve gut health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, emulsions stabilized by octenyl succinic anhydride-modified broken japonica rice starch (OSA-BJRS) were prepared at different ultrasonic power intensities for the delivery, controlled release, and improved bioavailability of quercetin. The OSA-BJRS emulsions ultrasonicated at 400 W exhibited the highest encapsulation efficiency (89.37 %) and loading efficiency (58.34 %) of quercetin, the smallest volume-average droplet diameter (0.51 μm) and polydispersity index (0.19), the highest absolute value of the ζ-potential (26.73 mV), and the highest apparent viscosity and viscoelasticity. The oxidation stability, storage stability, thermal stability, and salt ion stability of the emulsions were also notably improved by the ultrasonication treatment. In addition, the results of the simulated in vitro digestion demonstrated that the ultrasonicated OSA-BJRS emulsions had an enhanced quercetin delivery performance and could stably transport quercetin to the small intestine for digestion. The OSA-BJRS emulsion ultrasonicated at 400 W exhibited the highest cumulative release rate (95.91 %) and the highest bioavailability (30.48 %) of quercetin. This suggests that OSA-BJRS emulsions prepared by ultrasonication can be considered effective delivery systems for hydrophobic functional components., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Low bioavailability of quercetin (Que) reduces its preclinical and clinical benefits. In order to improve Que bioavailability, a novel whey protein isolate (WPI)-zein nanogel was prepared by pH-driven self-assembly and heat-induced gelatinization. The results showed that hydrochloric acid can be substituted by both acetic acid and citric acid during the pH-driven process. After encapsulation, the bioavailability of Que in nanogels (composed of 70 % WPI) induced by different acidifiers increased to 19.89 % (citric acid), 21.65 % (hydrochloric acid) and 24.34 % (acetic acid), respectively. Comparatively, nanogels induced by acetic acid showed higher stability (pH and storage stability), re-dispersibility (75.62 %), Que bioavailability (24.34 %), and antioxidant capacity (36.78 % for DPPH scavenging rates). s improved performance of nanogels. In mechanism, acetic acid significantly balanced different intermolecular forces by weakening "acid-induced denaturation" effect. Moreover, the faster binding of Que and protein as well as higher protein molecular flexibility and randomness (higher ratio of random coil) was also observed in nanogels induced by acetic acid. All of these changes contributed to improve nanogels performances. Overall, WPI-zein nanogels induced by acetic acid might be a safe, efficiency and stable delivery system to improve the bioavailability of hydrophobic active ingredients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bacterial infection, hyperinflammation and hypoxia, which can lead to amputation in severe cases, are frequently observed in diabetic wounds, and this has been a critical issue facing the repair of chronic skin injuries. In this study, a copper-based MOF (TAX@HKUST-1) highly loaded with taxifolin (TAX) with a drug loading of 41.94 ± 2.60 % was prepared. In addition, it has excellent catalase activity, and by constructing an oxygen-releasing hydrogel (PTH) system with calcium peroxide (CaO 2 ), it can be used as a nano-enzyme to promote the generation of oxygen from hydrogen peroxide (H 2 O 2 ) to provide sufficient oxygen to the wound, and at the same time, solve the problem of the oxidative stress damage caused by excess H 2 O 2 to the cells during the oxygen-releasing process. On the other hand, TAX and HKUST-1 in PTH synergistically promoted antimicrobial and anti-oxidative stress properties, and the bacterial inhibition rate against Staphylococcus aureus and Escherichia coli reached 90 %. In vivo experiments have shown that PTH hydrogel is able to treat diabetic skin repair by inhibiting the expression of inflammation-related proteins and promoting epidermal neogenesis, angiogenesis and collagen deposition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (-25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Availability of data and materials. All data used to support the findings of this study are available from the corresponding author upon request., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Quercetin (Q) has many potential health benefits, but its low stability limits its use in functional foods and pharmaceuticals. The low stability of quercetin is a challenge that needs to be addressed to fully realize its therapeutic potential. The purpose of this study was therefore to design a proper carrier based on porous starch (PS) and inulin (IN) in order to improve the stability of Q. The scanning electron microscopy (SEM) images denoted that the Q molecules were adsorbed in the PS pores and partially adhered to the surface of the granules. Both types of the wall material could remarkably enhance the protection of Q against thermal and light degradation. The retention index of Q under different environmental conditions was higher for the PS:IN-Q than PS-Q. The results of Fourier transform infrared spectroscopy (FT-IR) revealed that Q interacted with the wall materials through non-covalent bonds. X-ray diffraction (XRD) also confirmed the encapsulation of Q in the wall materials. The bonding between Q and the hydrogen groups of starch compacted the crystalline regions and increased the relative crystallinity in PS-Q and PS:IN-Q. The DPPH and ABTS scavenging activities of the microcapsules containing the PS and IN were higher than those of free Q. Examination of the in-vitro release profile indicated that the Q release rate was lower from the PS:IN-Q microcapsules (21.6%) than from the PS-Q ones (33.7%). Our findings highlight the significant potential of this novel biopolymer mixture (PS/IN) as a promising wall material for the protection and delivery of bioactive compounds., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study comprises the isolation of quercetin from the bhimkol banana (Musa balbisiana) blossom, encapsulation, and its characterizations. An isolated quercetin rich fraction was obtained from HPLC followed by column chromatography and subsequently encapsulated with chitosan-alginate polyelectrolyte complex at optimum encapsulation conditions obtained by ant colony optimization. Quercetin fraction and encapsulated quercetin were characterized for their physicochemical properties (by HPLC, FTIR, NMR, XRD, Dynamic Light Scattering, and release study). The yield and purity of isolated quercetin rich fractions were 2.35 ± 0.08 μg/ml and 83.12 ± 0.31 %, respectively. After the optimization of encapsulation, quercetin 0.2 %, sodium alginate 4 %, chitosan 0.5 %, and agitation at 300 rpm were found to be the optimal conditions resulting in higher encapsulation efficiency (EE, 84.54 %). EE was significantly improved by a slight increase in sodium alginate, and agitation. Encapsulated quercetin revealed good pH resistance by releasing 68.27 mg QE/g quercetin in simulated gastric fluid at 60 min. Microbeads of encapsulated quercetin showed the structural bond stretching of encapsulating materials and quercetin in FTIR spectra (stretching at 1511 cm -1 , 1380 cm -1 , and 1241 cm -1 are attributed to the stretching vibration of CO in aromatic rings, and bending vibration of OH bond in phenols). An average particle size of 2.71 μm exhibited the microgel behavior of microbeads (by XRD). The present study on the underutilized variety of banana blossoms has diverse applications in the food and pharmaceutical industries that will productively exhibit effective drug delivery properties., Competing Interests: Declaration of competing interest The author declare that no financial assistance received from any funding source. The authors declare no conflict of interest. All the authors have thoroughly read and approved the manuscript for submission. All the authors assure that the content of this manuscript has not been published, nor submitted for publication elsewhere., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Human serum albumin (HSA) is a serum protein that carries flavonoids in blood circulation. In this report, the binding selectivity and strength of interactions to HSA-binding sites (sites I or II) by flavonoids were evaluated using competition experiments and the specific fluorescent dyes, dansylamide and BD140. Most tested flavonoids bound site I preferentially, with the binding strength dependent on the mother structure in the order flavonol > flavone > flavanone > flavan 3-ols. Glycosylation or glucuronidation reduced the binding of quercetin to site I of HSA, whereas sulfation increased binding. Quercetin 7-sulfate showed the strongest binding and molecular docking simulations supported this observation. Prenylation at any position or glucuronidation and sulfation at the C-4' or C-7 position of quercetin facilitated stronger binding to site II. The binding affinity of flavonoids toward site I correlated with the partition coefficient value (logP), whereas no corresponding correlation was observed for site II., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Novel biocompatible and effective hyperthermia (HT) treatment materials for breast cancer therapeutic have recently attracting researchers, because of their effective ablation of cancer cells and negligible damage to healthy cells. Magnetoliposome (MLs) have numerous possibilities for utilize in cancer treatment, including smart drug delivery (SDD) mediated through alternating magnetic fields (AMF). In this work, magnesium ferrite (MgFe 2 O 4 ) encapsulated with liposomes lipid bilayer (MLs), Quercetin (Q)-loaded MgFe 2 O 4 @Liposomes (Q-MLs) nano-hybrid system were successfully synthesized for magnetic hyperthermia (MHT) and SDD applications. The hybrid system was well-investigated by different techniques using X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), Energy dispersive X-ray (EDX), Vibrating sample magnetometer (VSM), Transmission electron microscope (TEM), and Zeta Potential (ZP). The characterization results confirmed the improving quercetin-loading on the MLs surface. TEM analysis indicated the synthesized MgFe 2 O 4 , MLs, and Q-MLs were spherical with an average size of 23.7, 35.5, and 329.5 nm, respectively. The VSM results revealed that the MgFe 2 O 4 exhibit excellent and effective saturation magnetization (M S ) (40.5 emu/g). Quercetin drug loading and entrapment efficiency were found to be equal to 2.1 ± 0.1% and 42.3 ± 2.2%, respectively. The in-vitro Q release from Q-loaded MLs was found 40.2% at pH 5.1 and 69.87% at pH 7.4, verifying the Q-loading pH sensitivity. The MLs and Q-MLs hybrid system as MHT agents exhibit specific absorption rate (SAR) values of 197 and 205 W/g, correspondingly. Furthermore, the Q-MLs cytotoxicity was studied on the MCF-7 breast cancer cell line, and the obtained data demonstrated that the Q-MLs have a high cytotoxicity effect compared to MLs and free Q., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests relevant to study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chemoresistance, a significant challenge in cancer treatment, is often associated with the cellular glutathione-related detoxification system. The GSTP1 isoenzyme (glutathione S-transferases) plays a critical role in the cytoplasmic inactivation of anticancer drugs. This suggests the identification of GSTP1 inhibitors to combat chemoresistance. We screened Sophoretin (also called quercetin) derivatives for molecular properties, pharmacokinetics, and toxicity profiles. Following that, we conducted molecular docking and simulations between selected derivatives and GSTP1. The best-docked complex, GSTP1-quercetin 7-O-β-D-glucoside, exhibited a binding affinity of -8.1 kcal/mol, with no predicted toxicity and good pharmacokinetic properties. Molecular dynamics simulations confirmed the stability of this complex. Quercetin 7-O-β-D-glucoside shows promise as a lead candidate for addressing chemoresistance in cancer patients, although further experimental studies are needed to validate its efficacy and therapeutic potential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tartary buckwheat protein-rutin/quercetin covalent complex was synthesized in alkaline oxygen-containing environment, and its binding sites, conformational changes and functional properties were evaluated by multispectral technique and proteomics. The determination of total sulfhydryl and free amino groups showed that rutin/quercetin can form a covalent complex with BPI and could significantly reduce the group content. Ultraviolet-visible spectrum analysis showed that protein could form new characteristic peaks after binding with rutin/quercetin. Circular dichroism spectrum analysis showed that rutin and quercetin caused similar changes in the secondary structure of proteins, both promoting β-sheet to α-helix, β-ture and random coil transformation. The fluorescence spectrometry results showed that the combination of phenols can cause the fluorescence quenching, and the combination of rutin was stronger than the quercetin. Proteomics showed that there were multiple covalent binding sites between phenols and protein. Rutin had a high affinity for arginine, and quercetin and cysteine had high affinity. Meanwhile, the combination of rutin/quercetin and protein had reduced the surface hydrophobic ability of the protein, and improved the foaming, stability and antioxidant properties of the protein. This study expounded the mechanism of the combination of BPI and rutin/quercetin, and analysed the differences of the combination of protein and phenols in different structures. The findings can provide a theoretical basis for the development of complexes in the area of food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Fucoidan (FU), a natural marine polysaccharide, is an immunomodulator with great potential in tumor immunotherapy. In this work, a FU encapsulated nanoparticle named QU@FU-TS was developed, which contained the anticancer phytochemical quercetin (QU) and had the potential for cancer chemo-immunotherapy. QU@FU-TS were constructed through molecular self-assembly using green material tea saponin (TS) as the linking molecule. The molecular dynamics (MD) simulation showed that QU was bound to the hydrophobic tail of TS. At the same time, FU spontaneously assembled with the hydrophilic head of TS to form the outer layer of the QU@FU-TS. The molecular interactions between QU and TS were mainly π-stacking and hydrogen bonds. The bonding of FU and TS was maintained through the formation of multiple hydrogen bonds between the sulfate ester group and the hydroxy group. The inhibitory effects of QU@FU-TS on A549 cell proliferation were more potent than that by free QU. The antitumor activity of QU@FU-TS was mediated through various mechanisms, including the induction of oxidative stress, blocking cell cycle progression, and promoting cell apoptosis. Moreover, QU@FU-TS has been demonstrated to impede the proliferation and migration of cancer cells in vivo. The expression levels of macrophage surface markers increased under the treatment of QU@FU-TS, suggesting the potential of QU@FU-TS to serve as an immunotherapeutic agent by promoting macrophage activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

New Quercetin-phenylalanine metal-based therapeutic agents of the formulation [Qu(Phe)M(II).(H 2 O) 2 ].NO 3 where M(II) = Co(II) and Ni(II) and [Qu(Phe)Cu(II).(H 2 O) 2 ] were synthesized and their structure was predicted by IR, UV-vis, EPR and ESI-MS spectroscopic techniques. The bio-molecular interaction studies of the Quercetin-phenylalanine complexes, 1-3 with ct-DNA and BSA were performed using a battery of complimentary biophysical techniques. The corroborative results of these experiments revealed strong binding propensity via electrostatic interactions probably through minor grove binding towards ct-DNA, therapeutic target. The binding affinity of Quercetin-phenylalanine complexes 1-3 was quantified by determining binding constants values, K b , K sv , and the magnitude of binding propensity followed the order 3 > 1 > 2, implicating the preferential binding of Cu(II) complex 3 with ct-DNA. The cleavage studies were performed with complexes using gel electrophoretic mobility assay. The complexes 1-3 demonstrated efficient cleaving ability by the hydrolytic cleavage pathway involving hydroxyl (OH) radicals. BSA binding profile of Quercetin-phenylalanine metal therapeutics 1-3 was studied in order to understand the drug carrier potential of these compounds and found that complex 3 was capable of binding preferentially with BSA as compared to other complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The appropriateness of animal by-product proteins as emulsifiers is barely explored compared to their meat counterparts. This paper focused on improving interfacial and emulsifying properties of modified goose liver protein using three structurally relevant polyphenols either enhanced by pH shifting (P-catechin, P-quercetin and P-rutin) or not (catechin, quercetin and rutin). Due to its high hydrophobicity and limited steric hindrance, quercetin was more sufficient to hydrophobically interact (ΔH > 0, ΔS > 0) with MGLP than catechin and rutin. Results showed that polyphenol interactive affinity was positively correlated to surface hydrophobicity but negatively to size and aggregation extent of MGLP. Interfacial pressure and dilatational elastic modulus implied that synergistic polyphenol interaction and pH shifting favored the interfacial adsorption and macromolecular association of MGLP, particularly for P-quercetin with the values reached to 19.9 ± 2.0 mN/m and 22.9 ± 1.2 mN/m, respectively. Emulsion stabilized by P-quercetin also maintained highest physical and oxidative stabilities regarding the lowest D [4,3] (3.78 ± 0.27 μm) and creaming index (8.38 ± 0.43 %), together with highest mono- (19.51 %) and polyunsaturated fatty acid content (29.39 %) during storage. Overall, chemical structure of polyphenols may be determining in fabricating MGLP-polyphenol complexes with improved emulsion stabilization efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Brain cancer is the major reason of cancer-relevant deaths every year, as it is the most challenging cancer to treat and drug delivery. Quercetin (QUR), as a flavonoid substance found in plants and fruits, has good anticancer and medicinal effects on brain tumors, but its low stability and bioavailability as well as the blood-brain barrier (BBB), prevent it from reaching brain tumors. This research has introduced a nanocomposite made of biocompatible polymers, chitosan, and carboxymethyl cellulose. This co- biopolymer's mechanical and chemical properties and drug-loading capacity have been improved by adding zinc oxide nanoparticles (ZnO NPs). In addition, graphene quantum dots (GQDs) were used to improve the chemical properties as well as the ability to penetrate the BBB. The CS/CMC/GQDs/ZnO@QUR nanocomposites have nanoneedle structures with an average size of 219.38 ± 5.21 nm and a zeta potential of -53 mV. The morphology, chemical bonds, and crystallinity of the nanocomposite were examined by FE-SEM, FTIR, and XRD analyses, respectively. By examining the release of QUR, it became apparent that the half-drug release takes about 72 h, which has a much more controlled release than other QUR carriers. Further, the MTT test on U-87 MG and L929 cell lines suggested that this nanocomposite has good anticancer properties and low cytotoxicity compared to the free QUR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In order to efficiently improve the colon-targeted delivery of quercetin, the hydrophobic core-shell nanofibers were fabricated to encapsulate quercetin using ethyl cellulose as the shell and zein as the core by coaxial electrospinning. The encapsulation efficiency of coaxial nanofibers reached >97 %. FTIR and XRD results revealed the interactions between quercetin and wall materials and quercetin was encapsulated in an amorphous state. The thermal stability and surface hydrophobicity of coaxial nanofibers were improved compared to the uniaxial zein fibers. After in vitro gastrointestinal digestion, the quercetin release from core-shell nanofibers was <12.38 %, while the corresponding value for zein fibers was 36.24 %. DPPH and FRAP assays showed that there was no significant difference in the antioxidant activity of quercetin before and after encapsulation. Furthermore, the encapsulated quercetin exhibited similar anti-proliferative activity against HCT-116 cells compared to the free form. The results suggest these coaxial nanofibers have potential applications in functional foods., Competing Interests: Declaration of competing interest There have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Colorectal cancer is among the frequently diagnosed cancers with high mortality rates around the world. Polyphenolic compounds such as flavonoids are secondary plant metabolites which exhibit anti-cancer activities along with anti-inflammatory effects. However, due to their hydrophobicity, sensitivity to degradation and low bioavailability, therapeutic effects have shown poor therapeutic effect. Nano delivery systems such as nanoliposomes, nanomicelles, silica nanoparticles have been investigated to overcome these difficulties. This review provides a summary of the efficiency of certain flavonoids and polyphenols (apigenin, genistein, resveratrol, quercetin, silymarin, catechins, luteolin, fisetin, gallic acid, rutin, and curcumin) on colorectal cancer models. It comprehensively discusses the influence of nano-formulation of flavonoids on their biological functions, including cellular uptake rate, bioavailability, solubility, and cytotoxicity, as well as their potential for reducing colorectal cancer tumor size under in vivo situations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

In this study, a simple approach was used for the synthesis of a water-soluble hyaluronic acid-quercetin (HA-Q) pendant drug conjugate to evaluate its potential wound-healing properties. The HA-Q conjugation was confirmed by Fourier-transform infrared spectroscopy (FTIR), ultraviolet-visible spectrophotometry (UV-Vis), and nuclear magnetic resonance (NMR) spectroscopy techniques. To produce the HA-Q, quercetin was conjugated on the HA backbone to the extent of 44.7 %. The HA-Q conjugate was soluble in water and a solution with a concentration of 20 mg/ml was prepared. The conjugate exhibited good biocompatibility and supported the growth and cell migration of skin fibroblast cells. HA-Q presented improved radical scavenging capacity compared to quercetin (Q) alone. The overall results confirmed the potential role of HA-Q in wound healing applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To investigate the effects of structure, multiple binding sites and antioxidant property of Tartary buckwheat protein-phenols covalent complex, protein was combined with different concentrations of phenolic extract. Four kinds of phenols were identified by UPLC-Q/TOF-MS, which were rutin, quercetin, kaempferol and myricetin. UV-vis absorption spectroscopy and X-ray diffraction showed that the phenols can successfully bind to BPI. Fourier-transform infrared, circular dichroism and fluorescence emission spectroscopy showed that the binding of phenol can change the secondary/tertiary structure of protein. The particle distribution indicated that the binding of phenols could reduce the particle size (from 304.70 to 205.55 nm), but cross-linking occurred (435.35 nm) when the bound phenol content was too high. Proteomics showed that only rutin, quercetin and myricetin can covalently bind to BPI. Meanwhile, 4 peptides covalently bound to phenols were identified. The DPPH· scavenging capacity of complexes were from 8.38 to 33.76 %, and the ABTS· + binding activity of complexes were from 19.35 to 63.99 %. The antioxidant activity of the complex was significantly higher than that of the pure protein. These results indicated that protein-phenol covalent complexes had great potential as functional components in the food field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Inhibiting the activity of α-amylase has been considered an effective strategy to manage hyperglycemia. Hyperoside and quercetin are the main natural flavonoids in various plants, and the inhibition mechanism on α-amylase remains unclear. In this study, the structure-activity relationships between hyperoside/quercetin and α-amylase were evaluated by enzyme kinetic analysis, multi-spectroscopic techniques, and molecular docking analysis. Results showed that hyperoside and quercetin exhibited significant α-amylase inhibitory activities with IC 50 values of 0.491 and 0.325 mg/mL, respectively. The α-amylase activity decreased in the presence of hyperoside and quercetin in a competitive and noncompetitive manner, respectively. UV-vis spectra suggested that the aromatic amino acid residues (Trp and Tyr) microenvironment of α-amylase changed in the presence of these two flavonoids. FTIR and CD spectra showed the vibrations of the amide bands and the secondary structure content changes. The fluorescence quenching mechanism of α-amylase by hyperoside and quercetin belonged to the static quenching type. Finally, molecular docking intuitively showed that hyperoside/quercetin formed hydrogen bonds with the key active site residues (Asp197, Glu233, and Asp300) in α-amylase. MD simulation indicated hyperoside/quercetin-α-amylase docked complexes had good stability. Taken together, this research provides new sights to developing potent drugs or functional foods with hyperoside and quercetin, offering new avenues for hyperglycemia treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: The novel coronavirus disease-2019 (COVID-19) that emerged in China, is an extremely contagious and pathogenic viral infection caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that has sparked a global pandemic. The few and limited availability of approved therapeutic agents or vaccines is of great concern. Urgently, Remdesivir, Nirmatrelvir, Molnupiravir, and some phytochemicals including polyphenol, flavonoid, alkaloid, and triterpenoid are applied to develop as repurposing drugs against the SARS-CoV-2 invasion., Methods: This study was conducted to perform molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis of the potential phytocompounds and repurposing drugs against three targets of SARS-CoV-2 proteins (RNA dependent RNA polymerase, RdRp, Endoribonclease, S-protein of ACE2-RBD)., Results: The docking data illustrated Arachidonic acid, Rutin, Quercetin, and Curcumin were highly bound with coronavirus polyprotein replicase and Ebolavirus envelope protein. Furthermore, anti- Ebolavirus molecule Remedesivir, anti-HIV molecule Chloroquine, and Darunavir were repurposed with coronavirus polyprotein replicase as well as Ebolavirus envelope protein. The strongest binding interaction of each targets are Rutin with RdRp, Endoribonclease with Amentoflavone, and ACE2-RBD with Epigallocatechin gallate., Conclusions: Taken altogether, these results shed a light on that phytocompounds have a therapeutic potential for the treatment of anti-SARS-CoV-2 may base on multi-target effects or cocktail formulation for blocking viral infection through invasion/activation, transcription/reproduction, and posttranslational cleavage to battle COVID-19 pandemic., Competing Interests: Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

The present work aims at evaluating the in vitro biocompatibility, antibacterial activity and antioxidant capacity of the fabricated and optimized Alginate/Chitosan nanoparticles (ALG/CSNPs) and quercetin loaded Alginate/Chitosan nanoparticles (Q-ALG/CSNPs) with an improved biological efficacy on the hydrophobic flavonoid.The physicochemical properties were determined by TEM and FTIR analysis. The nanoparticles evaluated for the encapsulation of quercetin exerted % encapsulation efficiency (EE) that varied between 76 and 82.4 % and loading capacity (LC) from 31 to 46.5 %. Potential cytotoxicity of the ALG/CSNPs and Q-ALG/CSNPs upon L929 fibroblast cell line was evaluated by MTT reduction Assay and expressed as % cell viability. The in vitro antibacterial property was studied by well diffusion method against gram-positive bacteria Staphylococcus aureus (ATCC 25925) and gram-negative bacteria Escherichia coli (ATCC 25923). The inhibitory efficacy by scavenging free radical intermediates was evaluated by 1,1, diphenyl 2-picrylhydrazyl (DPPH) assay. The results of in vitro cytotoxicity showed biocompatibility towards L929 cells. Quercetin loaded Alginate/Chitosan nanoparticles inhibited the growth of microorganisms than pure quercetin. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging results have shown a high level of antioxidant property for encapsulated Quercetin in Alginate/Chitosan nanoparticles compared to free Quercetin. The findings of our study suggest that the developed ALG/CSNPs and Q-ALG/CSNPs possess the prerequisites and be proposed as a suitable system for delivering quercetin with enhanced therapeutic effectuality., Competing Interests: Declaration of competing interest The author hereby declares there is NO conflicts of interest in this work., (Copyright © 2022. Published by Elsevier B.V.)

Quercetin is one of the most bioactive and common dietary flavonoids, with a significant repertoire of biological and pharmacological properties. The biological activity of quercetin, however, is influenced by its limited solubility and bioavailability. Driven by the need to enhance quercetin bioavailability and bioactivity through metal ion complexation, synthetic efforts led to a unique ternary Ce(III)-quercetin-(1,10-phenanthroline) (1) compound. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetric analysis (TGA), UV-Visible, NMR, Electron Spray Ionization-Mass Spectrometry (ESI-MS), Fluorescence, X-rays) revealed its solid-state and solution properties, with significant information emanating from the coordination sphere composition of Ce(III). The experimental data justified further entry of 1 in biological studies involving toxicity, (Reactive Oxygen Species, ROS)-suppressing potential, cell metabolism inhibition in Saccharomyces cerevisiae (S. cerevisiae) cultures, and plasmid DNA degradation. DFT calculations revealed its electronic structure profile, with in silico studies showing binding to DNA, DNA gyrase, and glutathione S-transferase, thus providing useful complementary insight into the elucidation of the mechanism of action of 1 at the molecular level and interpretation of its bio-activity. The collective work projects the importance of physicochemically supported bio-activity profile of well-defined Ce(III)-flavonoid compounds, thereby justifying focused pursuit of new hybrid metal-organic materials, effectively enhancing the role of naturally-occurring flavonoids in physiology and disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

AL amyloidosis is a life-threatening disease characterized by the deposition of amyloidogenic immunoglobulin light chain secreted from clonal plasma cells. Here we established an in-vitro screening system of amyloid inhibition of a variable domain in λ6 light chain mutant (Vλ6), Wil, and screened a food-additive compound library to identify compounds inhibiting the fibril formation. We found gossypetin and isoquercitrin as novel inhibitors. NMR analysis showed that both compounds directly interacted with natively-folded Wil, and proteolysis experiments demonstrated that these compounds conferred proteolytic resistance, suggesting that the compounds enhance the kinetic stability of Wil. Since gossypetin and isoquercitrin specifically interacted with the protein at micromolar concentrations, these compounds could be used as lead to further develop inhibitors against AL amyloidosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with the contents of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Since glucolipid metabolism disorders is often the mono-target therapy fails in managing blood glucose and lipid levels and the other complications, it is urgent and necessary to seek for the new potential drugs or functional food acting on multi-targets. The hypoglycemic and hypolipidemic dual activities of the root, stems and leaves of Desmodium caudatum, which is used for traditional Chinese medicine, was evaluated. Twelve extracts with different extraction conditions were prepared and extract 9 was find to exhibit potential inhibitory activities of fructose-1, 6-bisphosphatase (FBPase), α-glucosidase, and pancrelipase, as well as promote cellular glucose consumption and reduce cellular content of lipid. Five flavonoids were isolated and identified from extract 9, among which 8-prenylquercetin exhibited potent α-glucosidase (IC 50  = 4.38 μM) and FBPase (IC 50  = 3.62 μM) dual inhibitory activity, which were 75-fold higher than acarbose (IC 50  = 330.10 μM) and comparable with AMP (IC 50  = 2.92 μM). In addition, 8-prenylquercetin was able to promote glucose consumption and reduce lipid content. Besides, an efficient synthesis of the most potent 8-prenylquercetin was developed from inexpensive and commercially available rutin in 21% overall yield by 6 steps, which lay the foundation of preparation sufficient amount for follow-up study., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Quercetin 2,4-dioyxgenase (QueD) has been known to catalyze the oxygenative degradation of flavonoids and quercetin. Recent crystallographic study revealed a nickel ion occupies the active site as a co-factor to support O 2 activation and catalysis. Herein, we report a nickel(II) flavonolate complex bearing a tridentate macrocyclic ligand, [Ni II (Me 3 -TACN)(Fl)(NO 3 )](H 2 O) (1, Me 3 -TACN = 1,4,7-trimethyl-1,4,7-triazacyclononane, Fl = 3-hydroxyflavone) as a functional model for QueD. The flavonolatonickel(II) complex was characterized by using spectrometric analysis including UV-vis spectroscopy, electrospray ionization mass spectrometer (ESI-MS), infrared spectroscopy (FT-IR) and 1 H nuclear magnetic resonance spectroscopy (NMR). The single crystal X-ray structure of 1 shows two isomers with respect to the direction of a flavonolate ligand. Two isomers commonly are in the octahedral geometry with a bidentate of flavonolate and a monodentate of nitrate as well as a tridentate binding of Me 3 -TACN ligand. The spin state of 1 is determined to be a triplet state based on the Evans' method. Interestingly, electronic configuration of 1 from density functional theory (DFT) calculations revealed that the two singly occupied molecular orbitals (SOMOs) lie energetically lower than the highest (doubly) occupied molecular orbital (HOMO), that is so-called the SOMO-HOMO level inversion (SHI). The HOMO shows an electron density localized in the flavonolate ligand, indicating that flavonolate ligand is oxidized first rather than the nickel center. Thermal degradation of 1 resulted in the formation of benzoic acid and salicylic acid, which is attributed to the oxygenation of flavonolate of 1., (Copyright © 2021. Published by Elsevier Inc.)