Myricetin and its derivatives, myricitrin and dihydromyricetin, are flavonoids widely presented in foods and phytomedicine that possess tremendous health potential. In this study, we compared the antiglycation activity of myricetin and its derivatives, then investigated the underlying mechanism using proteomic modification and fluorescence spectroscopy analysis. All three compounds exhibited thorough inhibition on nonenzymatic glycation process, with the inhibitory effects on AGEs reaching 85% at 40 μmol/L. They effectively protected bovine serum albumin (BSA) structure by inhibiting protein oxidation, preventing the conversion from α-helix to β-sheet, and reducing amyloid-like cross-β structure formation. Among the three compounds, myricetin showed a predominant antiglycation activity. Proteomic analysis identified the early glycated sites that were protected by myricetin, including lysine K235, 256, 336, 421, 420, 489, etc. Additionally, fluorescence spectroscopy revealed spontaneous interactions between BSA and myricetin. Overall, myricetin holds promise as an antiglycation agent in both the food and drug industries.

Breast cancer (BC) is the second-leading cause of cancer after lung cancer. The disease has affected millions of people and resulted in many deaths. In the metastasis of breast cancer cells, Topoisomerase IIα plays a vital role. Therefore, this investigation aims to identify potential flavonoid compounds against BC by inhibiting this enzyme at an early stage. Based on previous studies, we selected and screened several plant-derived flavonoid compounds with potential anti-breast cancer activity using PyRx 0.8 and Schrodinger applications for preliminary molecular docking: the highest docking scores of Myricetin (-11.6 kcal/mol) and Quercetin (-10.0 kcal/mol). Next, we evaluated the top four compounds on the Way2Drug server to complete the cytotoxicity evaluation, which demonstrated anti-cancer and anti-breast cancer activity in various cell lines. According to pharmacokinetics studies, four compounds exhibited outstanding values and functioned similar to drug-like molecules. Moreover, Myricetin, Quercetin, and Morin displayed the highest number of hydrogen bonds, with the corresponding receptor forming residues asn120, thr147, and lys168. The protein-ligand complexes were validated using the Desmond simulator, and their data were compared to the anti-breast cancer drug Doxorubicin. In the simulation analysis, various parameters were evaluated, including RMSD, RMSF, Rg, SASA, MolSA, PSA, and hydrogen bond interaction. Finally, validated our dynamic simulation result with MM-GBSA operation, and Myricetin and Quercetin had the greatest score of -72.74344651, -66.66771823 kcal/mol, which is outstanding than the control drug. Hence, the computational research approach determined that Myricetin, Quercetin, and Morin could be industrially developed for the alternative treatment of breast cancer following additional confirmation from animal and cell line studies.

UNASSIGNED: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity.
UNASSIGNED: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated.
UNASSIGNED: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 μg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group.
UNASSIGNED: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

The second most prevalent neurodegenerative disease, Parkinson\'s disease (PD), is caused by the accumulation and deposition of fibrillar aggregates of the α-Syn into the Lewy bodies. To create a potent pharmacological candidate to destabilize the preformed α-Syn fibril, it is important to understand the precise molecular mechanism underlying the destabilization of the α-Syn fibril. Through molecular dynamics simulations and experiments, we have examined the molecular mechanisms causing the destabilization and suppression of a newly discovered α-Syn fibril with a Greek-key-like shape and an aggregation prone state (APS) of α-Syn in the presence and absence of various Flvs. According to MD simulation and experimental evidence, morin, quercetin, and myricetin are the Flvs, most capable of destabilizing the fibrils and converting them into amorphous aggregates. Compared to galangin and kaempferol, they have more hydroxyl groups and form more hydrogen bonds with fibrils.The processes by which morin and myricetin prevent new fibril production from APS and destabilize the fibrils are different. According to linear interaction energy analysis, van der Waals interaction predominates with morin, and electrostatic interaction dominates with myricetin. Our MD simulation and experimental findings provide mechanistic insights into how Flvs destabilize α-Syn fibrils and change their morphology, opening the door to developing structure-based drugs for treating Parkinson\'s disease.

Myricetin (MYR) and myricitrin (MYT) are well recognized for their nutraceutical value, such as antioxidant, hypoglycemic, and hypotensive effects. In this work, fluorescence spectroscopy and molecular modeling were adopted to investigate the conformational and stability changes of proteinase K (PK) in the presence of MYR and MYT. The experimental results showed that both MYR and MYT could quench fluorescence emission via a static quenching mechanism. Further investigation demonstrated that both hydrogen bonding and van der Waals forces play significant roles in the binding of complexes, which is consistent with the conclusions of molecular modeling. Synchronous fluorescence spectroscopy, Förster resonance energy transfer, and site-tagged competition experiments were performed to prove that the binding of MYR or MYT to PK could alter its micro-environment and conformation. Molecular docking results revealed that either MYR or MYT spontaneously interacted with PK at a single binding site via hydrogen bonding and hydrophobic interactions, which is consistent with the results of spectroscopic measurements. A 30 ns molecular dynamics simulation was conducted for both PK-MYR and PK-MYT complexes. The calculation results showed that no large structural distortions or interaction changes occurred during the entire simulation time span. The average RMSD changes of PK in PK-MYR and PK-MYT were 2.06 and 2.15 Å, respectively, indicating excellent stability of both complexes. The molecular simulation results suggested that both MYR and MYT could interact with PK spontaneously, which is in agreement with spectroscopic results. This agreement between experimental and theoretical results indicates that the method herein could be feasible and worthwhile for protein-ligand complex studies.

We intended to identify favourable metabolite(s) and pharmacological mechanism(s) of gut microbiota (GM) for liver regeneration (LR) through network pharmacology. We utilized the gutMGene database to obtain metabolites of GM, and targets associated with metabolites as well as LR-related targets were identified using public databases. Furthermore, we performed a molecular docking assay on the active metabolite(s) and target(s) to verify the network pharmacological concept. We mined a total of 208 metabolites in the gutMGene database and selected 668 targets from the SEA (1,256 targets) and STP (947 targets) databases. Finally, 13 targets were identified between 61 targets and the gutMGene database (243 targets). Protein-protein interaction network analysis showed that AKT1 is a hub target correlated with 12 additional targets. In this study, we describe the potential microbe from the microbiota (E. coli), chemokine signalling pathway, AKT1 and myricetin that accelerate LR, providing scientific evidence for further clinical trials.

The COVID-19 pandemic has caused millions of fatalities since 2019. Despite the availability of vaccines for this disease, new strains are causing rapid ailment and are a continuous threat to vaccine efficacy. Here, molecular docking and simulations identify strong inhibitors of the allosteric site of the SARS-CoV-2 virus RNA dependent RNA polymerase (RdRp). More than one hundred different flavonoids were docked with the SARS-CoV-2 RdRp allosteric site through computational screening. The three top hits were Naringoside, Myricetin and Aureusidin 4,6-diglucoside. Simulation analyses confirmed that they are in constant contact during the simulation time course and have strong association with the enzyme\'s allosteric site. Absorption, distribution, metabolism, excretion and toxicity (ADMET) data provided medicinal information of these top three hits. They had good human intestinal absorption (HIA) concentrations and were non-toxic. Due to high mutation rates in the active sites of the viral enzyme, these new allosteric site inhibitors offer opportunities to drug SARS-CoV-2 RdRp. These results provide new information for the design of novel allosteric inhibitors against SARS-CoV-2 RdRp.

Myricetin is a common natural flavonoid compound with various pharmacological activities. However, the metabolite characterization of this substance is still inadequate. In this study, a simple and rapid system strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry combining parallel reaction monitoring mode was established to screen and identify myricetin metabolites in rat urine, plasma and faeces after oral administration. A total of 38 metabolites were fully or partially characterised based on their accurate mass, characteristic fragment ions, retention times, corresponding Clog P values, and so on. These metabolites were presumed to generate through glucuronidation, glucosylation, sulfation, dihydroxylation, acetylation, hydrogenation, hydroxylation and their composite reactions. In addition, the characteristic fragmentation pathways of flavonoids with more metabolites were summarised for the subsequent metabolite identification. The current study provided an overall metabolic profile of myricetin, which would be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.

We here report on flavonols (myricetin (MCE) and its glycoside myricitrin (MCI)) - 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membrane interactions focusing on the effects of flavonol clustering on the membrane thermotropic and nanomechanical properties. Atomic force microscopy (AFM), force spectroscopy (FS) and differential scanning calorimetry (DSC) together with molecular dynamics (MD) simulations provided a consistent picture of flavonol - DMPC membrane interactions. DMPC membrane as a supported lipid bilayer preserved its integrity even at higher flavonol molar fraction x. When present at x = 0.1 - 0.3, MCE and MCI both slightly improve DMPC bilayer fluidity which is evidenced by the decrease in the main phase transition temperature Tm. MCE is found within the interior of the bilayer, while MCI incorporates in the head group-water interface region. AFM and FS confirmed clusters as protrusions with an average height of 0.012 μm and average diameters of 0.60 and 0.24 μm for MCE and MCI clusters, respectively. The average membrane thickness in DMPC fluid phase decreases for 7% at xMCE = 0.30, while only 4% at xMCI = 0.27. The induced membrane changes are dependent on the chemical and physical properties of inserted flavonols. The hypothesis regarding the tendency of flavonol to clustering in membranes by increasing flavonol molar fraction has been confirmed.

Flavonoids, polyphenols with anti-oxidative activity have high potential as novel therapeutics for neurodegenerative disease, but their applicability is rendered by their poor water solubility and chemical instability under physiological conditions. In this study, this is overcome by delivering flavonoids to model cell membranes (unsaturated DOPC) using prepared and characterized biodegradable mesoporous silica nanoparticles, MSNs. Quercetin, myricetin and myricitrin have been investigated in order to determine the relationship between flavonoid structure and protective activity towards oxidative stress, i.e., lipid peroxidation induced by the addition of hydrogen peroxide and/or Cu2+ ions. Among investigated flavonoids, quercetin showed the most enhanced and prolonged protective anti-oxidative activity. The nanomechanical (Young modulus) measurement of the MSNs treated DOPC membranes during lipid peroxidation confirmed attenuated membrane damage. By applying a combination of experimental techniques (atomic force microscopy-AFM, force spectroscopy, electrophoretic light scattering-ES and dynamic light scattering-DLS), this work generated detailed knowledge about the effects of flavonoid loaded MSNs on the elasticity of model membranes, especially under oxidative stress conditions. Results from this study will pave the way towards the development of innovative and improved markers for oxidative stress-associated neurological disorders. In addition, the obtained could be extended to designing effective delivery systems of other high potential bioactive molecules with an aim to improve human health in general.