Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: 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. RESULTS: 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. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

Comparison of Alternative Protein Hydrogels for Delivering Myricetin: Interaction Mechanism and Stability Evaluation.

Food protein carriers from different sources might have distinct stabilizing and enhancing effects on the same small molecule. To elucidate the molecular mechanism, five different sourced proteins including soy protein isolates (SPIs), whey protein isolates (WPIs), edible dock protein (EDP), Tenebrio molitor protein (TMP), and yeast protein (YP) were used to prepare protein hydrogels for delivering myricetin (Myr). The results suggested that the loading capacity order of Myr in different protein hydrogels was EDP (11.5%) > WPI (9.3%) > TMP (8.9%) > YP (8.0%) > SPI (7.6%), which was consistent with the sequence of binding affinity between Myr and different proteins. Among five protein hydrogels, EDP had an optimum loading ability since it possessed the highest hydrophobic amino acid content (45.52%) and thus provided a broad hydrophobic cavity for loading Myr. In addition, these protein-Myr composite hydrogels displayed the core-shell structure, wherein hydrogen bonding and hydrophobic interaction were the primary binding forces between proteins and Myr. Moreover, the thermal stability, storage stability, and sustained-release properties of Myr were significantly enhanced via these protein delivery systems. These findings can provide scientific guidance for deeper utilization of food alternative protein sources.

Myricetin Amorphous Solid Dispersions-Antineurodegenerative Potential.

Our research aimed to develop an amorphous solid dispersion (ASD) of myricetin (MYR) with Polyvinylpyrrolidone K30 (PVP30) to enhance its solubility, dissolution rate, antioxidant, and neuroprotective properties. Employing a combination of solvent evaporation and freeze drying, we successfully formed MYR ASDs. XRPD analysis confirmed complete amorphization in 1:8 and 1:9 MYR-PVP weight ratios. DSC thermograms exhibited a single glass transition (Tg), indicating full miscibility. FT-IR results and molecular modeling confirmed hydrogen bonds stabilizing MYR's amorphous state. HPLC analysis indicated the absence of degradation products, ensuring safe MYR delivery systems. Solubility, dissolution rate (pH 1.2 and 6.8), antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays), and in vitro neuroprotective activities (inhibition of cholinesterases: AChE and BChE) were significantly improved compared to the pure compound. Molecular docking studies revealed that MYR had made several hydrogen, hydrophobic, and π-π stacking interactions, which could explain the compound's potency to inhibit AChE and BChE. MYR-PVP 1:9 w/w ASD has the best solubility, antioxidant, and neuroprotective activity. Stability studies confirmed the physical stability of MYR-PVP 1:9 w/w ASD immediately after dissolution and for two months under ambient conditions. Our study showed that the obtained ASDs are promising systems for the delivery of MYR with the potential for use in alleviating the symptoms of neurodegenerative diseases.

Flavonoids: A treasure house of prospective pharmacological potentials.

Flavonoids are organic compounds characterized by a range of phenolic structures, which are abundantly present in various natural sources such as fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. The health advantages of these natural substances are renowned, and initiatives are being taken to extract the flavonoids. Apigenin, galangin, hesperetin, kaempferol, myricetin, naringenin, and quercetin are the seven most common compounds belonging to this class. A thorough analysis of bibliographic records from reliable sources including Google Scholar, Web of Science, PubMed, ScienceDirect, MEDLINE, and others was done to learn more about the biological activities of these flavonoids. These flavonoids appear to have promising anti-diabetic, anti-inflammatory, antibacterial, antioxidant, antiviral, cytotoxic, and lipid-lowering activities, according to evidence from in vitro, in vivo, and clinical research. The review contains recent trends, therapeutical interventions, and futuristic aspects of flavonoids to treat several diseases like diabetes, inflammation, bacterial and viral infections, cancers, and cardiovascular diseases. However, this manuscript should be handy in future drug discovery. Despite these encouraging findings, a notable gap exists in clinical research, hindering a comprehensive understanding of the effects of flavonoids at both high and low concentrations on human health. Future investigations should prioritize exploring bioavailability, given the potential for high inter-individual variation. As a starting point for further study on these flavonoids, this review paper may promote identifying and creating innovative therapeutic uses.

Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4.

Ferroptosis holds great potential as a therapeutic approach for gastric cancer (GC), a prevalent and deadly malignant tumor associated with high rates of incidence and mortality. Myricetin, well-known for its multifaceted biomedical attributes, particularly its anticancer properties, has yet to be thoroughly investigated regarding its involvement in ferroptosis. The aim of this research was to elucidate the impact of myricetin on ferroptosis in GC progression. The present study observed that myricetin could trigger ferroptosis in GC cells by enhancing malondialdehyde production and Fe2+ accumulation while suppressing glutathione levels. Mechanistically, myricetin directly interacted with NADPH oxidase 4 (NOX4), influencing its stability by inhibiting its ubiquitin degradation. Moreover, myricetin regulated the inhibition of ferroptosis induced by Helicobacter pylori cytotoxin-associated gene A (CagA) through the NOX4/NRF2/GPX4 pathway. In vivo experiments demonstrated that myricetin treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice. It was accompanied by increased NOX4 expression in tumor tissue and suppression of the NRF2/GPX4 antioxidant pathway. Therefore, this research underscores myricetin as a novel inducer of ferroptosis in GC cells through its interaction with NOX4. It is a promising candidate for GC treatment.

Comparative Analysis of Fluorescence Emission in Myricetin, Kaempferol, and Quercetin Powders and Solutions.

Myricetin is a flavonol with high antioxidant properties. In this research, the fluorescence emission of myricetin powder and its solutions in different solvents were measured and analyzed by comparing with the results of calculations. Comparison of the calculated and measured characteristic wavelengths allowed the identification of all the spectral features in the fluorescence spectra of myricetin powder and solutions with different concentrations. The computation was based on modeling the process of the excited state intermolecular proton transfer, which predicts the formation of tautomeric forms of the flavonol molecule. Characteristic emission wavelengths were obtained using TDDFT/M06-2X/6-31++G(d,p). To understand the influence of the hydroxyl groups in the B-ring of the flavonol molecule on the emission spectrum, we also compared the fluorescence spectra of myricetin with those of kaempferol and quercetin. Moreover, based on the analysis of the changes in the shape of the FL spectra with the concentration of the solution, a criterion for the complete dissolution of the flavonol powders was established, which is important for bioavailability of flavonoids.

Preparation of the Myricetin-Loaded PEGylated Niosomes and Evaluation of their in†vitro Anti-Cancer Potentials.

Several edible plants contain flavonoids, including myricetin (Myr), which perform a wide range of biological activities. Myr has antitumor properties against various tumor cells. In this study Myr-loaded PEGylated niosomes (Myr-PN) were prepared and their anti-cancer activities were evaluated in vitro. Myr-PNs were prepared as a tool for drug delivery to the tumor site. Myr-PN was characterized in terms of size, zeta potential, and functional groups using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The Myr-PN size was 241 nm with a polydispersity index (PDI) of 0.20, and zeta potential -32.7±6.6 mV. Apoptotic properties of Myr-PN against normal and cancer cell lines were determined by flow cytometry and real-time quantitative PCR. Cancer cells showed higher cytotoxicity when treated with Myr-PN compared with normal cells, indicating that the synthesized nanoparticles pose no adverse effects. Apoptosis was induced in cells treated with 250 µg/mL of Myr-PN, in which 45.2 % of cells were arrested in subG1, suggesting that Myr-PN can induce apoptosis. In vitro, the synthesized Myr-PN demonstrated potent anticancer properties. Furthermore, more research should be conducted in vitro and in vivo to study the more details of Myr-PN anti-cancer effects.

Molecular Docking and Absorption, Distribution, Metabolism, and Excretion (ADME) Analysis: Examining the Binding Modes and Affinities of Myricetin With Insulin Receptor, Glycogen Synthase Kinase, and Glucokinase.

Aim By using molecular docking analysis (MDA) to examine its interactions with important regulatory proteins linked to diabetes, such as glycogen synthase kinase 3 beta (GSK3ß), insulin receptor (IR), and glucose kinase (GCK), this study seeks to explore the therapeutic potential of myricetin, a naturally occurring flavonoid. Objective The main goal is to determine potential effects on insulin signalling, GSK3ß activity, and glucose metabolism by evaluating the binding affinities of myricetin with GCK, IR, and GSK3ß through MDA. In order to assess the drug affinity of myricetin, the study also intends to perform absorption, distribution, metabolism, and excretion (ADME) studies. Materials and methods To model the interaction between myricetin and the target proteins (GCK, IR, and GSK3ß), we used molecular docking analysis with computational tools. ADME studies were also included in the study to evaluate drug affinity. Identification of binding sites, essential residues, and interaction stability were all part of the structural analysis. Results As evidence of possible interactions with these regulatory proteins, myricetin showed positive binding affinities with GCK, IR, and GSK3ß. Strong interactions with important ligand recognition residues were seen in the docking into IR, indicating a potential impact on insulin signalling. Moreover, a strong binding affinity for GCK indicated potential effects on the metabolism of glucose. Studies using ADME confirmed the high drug affinity of myricetin. Conclusion This work sheds light on the multi-target potential of myricetin in the regulation of diabetes. It appears that it has the ability to influence glucose metabolism, suppress GSK3ß activity, and regulate insulin signalling based on its interactions with IR, GSK3ß, and GCK. Although these computational results show promise, more experimental work is necessary to confirm and fully understand the precise mechanisms that underlie myricetin's effects on the regulation of diabetes.

Protective effects of myricetin and morin on neurological damage in Aß1-42/Al3+ -induced Alzheimer's disease model of rats.

Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Aß1-42 oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl3·6H2O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Aß, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Aß1-42/Al3+ through anti-oxidative stress and anti-apoptotic features.

Effects of myricetin and quercetin on ticagrelor metabolism and the underlying mechanism.

The aim of this study was to investigate the potential drug-drug interactions (DDIs) between ticagrelor and other drugs as well as their underlying mechanisms. Rat liver microsome (RLM) reaction system was used to screen potential DDIs in vitro, and ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to detect the levels of ticagrelor and AR-C124910XX, the main metabolite of ticagrelor. A total of 68 drugs were screened, 11 of which inhibited the production of AR-C124910XX to 20% or less, especially two flavonoids (myricetin and quercetin). The half-maximal inhibitory concentration (IC50) of myricetin on ticagrelor was 11.51 ± 0.28 µM in RLM and 17.96 ± 0.54 µM in human liver microsome (HLM). The IC50 of quercetin in inhibiting ticagrelor in RLM and HLM was 16.92 ± 0.49 µM and 60.15 ± 0.43 µM, respectively. They all inhibited the metabolism of ticagrelor through a mixed mechanism. In addition, Sprague-Dawley (SD) rats were used to study the interactions of ticagrelor with selected drugs in vivo. We found that the main pharmacokinetic parameters including AUC (0-t), AUC (0-∞) and Cmax of ticagrelor were significantly increased when ticagrelor was combined with these two flavonoids. Our results suggested that myricetin and quercetin of flavonoids both had significant effects on the metabolism of ticagrelor, providing reference data for the clinical individualized medication of ticagrelor.

Inhibition of amyloid-ß(16-22) aggregation by polyphenols using replica permutation with solute tempering molecular dynamics simulation.

Aggregates of amyloid-ß (Aß) peptides are thought to cause Alzheimer's disease. Polyphenolic compounds are known to inhibit Aß aggregation. We applied replica permutation with solute tempering (RPST) to the system of Aß fragments, Aß(16-22), and polyphenols to elucidate the mechanism of inhibition of Aß aggregation. The RPST molecular dynamics simulations were performed for two polyphenols, myricetin (MYC) and rosmarinic acid (ROA). Two Aß fragments were distant, and the number of residues forming the intermolecular ß-sheet was reduced in the presence of MYC and ROA compared with that in the absence of polyphenols. MYC was found to interact with glutamic acid and phenylalanine of Aß fragments. These interactions induce helix structure formation of Aß fragments, making it difficult to form ß-sheet. ROA interacted with glutamic acid and lysine, which reduced the hydrophilic interaction between Aß fragments. These results indicate that these polyphenols inhibit the aggregation of Aß fragments with different mechanisms.

Modified halloysite nanotubes as GRAS nanocarrier for intelligent monitoring and food preservation.

Conventional "all-in-one" methods for multi-component active packaging systems are not wholly adequate for fresh food. Given the need for multifunctional properties, introducing halloysite nanotubes (HNTs) could be a promising way to achieve controllable release of active ingredients while endowing with pH-sensitive performance. Here, we pioneered a GRAS composite with multifunctional properties, employing natural HNTs as a nanocarrier, citral (Cit) as an active antimicrobial agent, and myricetin (Myr) for monitoring freshness. The Cit-HNTs-Myr had excellent DPPH, ABTS and ·OH radical scavenging capacity, dual-model (contact and fumigant) antibacterial properties, and pH-sensitive performance. Subsequently, a smart tag prepared by dipping cellulose fibers into Cit-HNTs-Myr, which extended the shelf life of shrimp and blueberries, and provided freshness information for the shrimp. These results demonstrate the applicability of Cit-HNTs-Myr in the preservation of perishable goods and freshness monitoring.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway.

BACKGROUND: Development of end-stage renal disease is predominantly attributed to diabetic nephropathy (DN). Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue. Nevertheless, the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain. AIM: To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism. METHODS: Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk. Subsequently, blood and urine indexes were assessed, along with examination of renal tissue pathology. Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and Sirius-red. Additionally, high-glucose culturing was conducted on the RAW 264.7 cell line, treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h. In both in vivo and in vitro settings, quantification of inflammation factor levels was conducted using western blotting, real-time qPCR and ELISA. RESULTS: In db/db mice, administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis. Notably, we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin, along with a decrease in expressions of inflammatory cytokine-related factors. Furthermore, myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha, interleukin-6, and interluekin-1ß induced by high glucose in RAW 264.7 cells. Additionally, myricetin modulated the M1-type polarization of the RAW 264.7 cells. Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin. The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002. CONCLUSION: This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

In vivo Gonadoprotective Effects of Myricetin on Cisplatin- Induced Testicular Damage via Suppression of TLR4/NF-kB Inflammation Pathway and Heat-Shock Response / Efectos Gonadoprotectores in vivo de la Miricetina sobre el Daño Testicular Inducido por Cisplatino Mediante la Supresión de la Vía de Inflamación TLR4/NF-kB y la Respuesta al Choque Térmico

SUMMARY: The aim of this study is to reveal the gonadoprotective effects of myricetin (MYC), which has many biological properties, on cisplatin (CP)-induced testicular damage in rats. For this purpose, 40 male Wistar albino rats were divided into 4 groups as Control (group given no treatment), MYC (group given 5 mg/kg/i.p myricetin for 7 days), CP (group given 7 mg/kg/i.p cisplatin at 7th day) and MYC + CP (group given 5 mg/kg/i.p myricetin for 7 days before 7 mg/kg/i.p cisplatin injection). After administrations, testicular tissues of animals were extracted and processed according to tissue processing protocol. Hematoxylin & Eosin staining were performed to evaluate the histopathological changes and Johnsen'sTesticular Biopsy Score (JTBS) was applied and mean seminiferous tubule diameters (MSTD) were measured to compare experimental groups in terms of histopathological changes. Moreover, TLR4, NF-kB, HSP70 and HSP90 expression levels were detected by immunohistochemical staining and the density of immunoreactivity were measured to determine the difference in the expression levels of these factors among groups. Additionally, testicular apoptosis was detected via TUNEL assay. JTBS and MSTD data were significantly lower in CP group compared to other groups and MYC administrations significantly protects testicular tissue against CP-induced damage. Moreover, TLR4, NF-kB, HSP70 and HSP90 expressions and apoptotic cells significantly increased in the CP group (p<0.05). However, MYC administrations exerted a strong gonadoprotective effect on testicular tissue in terms of these parameters in MYC+CP group (p<0.05). According to our results, we suggested that MYC can be considered as a protective agent against cisplatin-induced testicular damage.

El objetivo de este estudio es revelar los efectos gonadoprotectores de la miricetina (MYC), que tiene muchas propiedades biológicas, sobre el daño testicular inducido por cisplatino (CP) en ratas. Para este propósito, se dividieron 40 ratas albinas Wistar macho en 4 grupos: Control (grupo que no recibió tratamiento), MYC (grupo que recibió 5 mg/kg/i.p de miricetina durante 7 días), CP (grupo que recibió 7 mg/kg/i.p de cisplatino al séptimo día) y MYC + CP (grupo que recibió 5 mg/ kg/i.p de miricetina durante 7 días antes de la inyección de 7 mg/ kg/i.p de cisplatino). Después de las administraciones, se extrajeron y procesaron tejidos testiculares de animales según el protocolo de procesamiento de tejidos. Se realizó tinción con hematoxilina y eosina para evaluar los cambios histopatológicos y se aplicó la puntuación de biopsia testicular de Johnsen (JTBS) y se midieron los diámetros medios de los túbulos seminíferos (MSTD) para comparar los grupos experimentales en términos de cambios histopatológicos. Además, los niveles de expresión de TLR4, NF-kB, HSP70 y HSP90 se detectaron mediante tinción inmunohistoquímica y se midió la densidad de inmunorreactividad para determinar la diferencia en los niveles de expresión de estos factores entre los grupos. Además, se detectó apoptosis testicular mediante el ensayo TUNEL. Los datos de JTBS y MSTD fueron significativamente más bajos en el grupo CP en comparación con otros grupos y las administraciones de MYC protegen significativamente el tejido testicular contra el daño inducido por CP. Además, las expresiones de TLR4, NF-kB, HSP70 y HSP90 y las células apoptóticas aumentaron significativamente en el grupo CP (p<0,05). Sin embargo, las administraciones de MYC ejercieron un fuerte efecto gonadoprotector sobre el tejido testicular en términos de estos parámetros en el grupo MYC+CP (p<0,05). Según nuestros resultados, sugerimos que MYC puede considerarse como un agente protector contra el daño testicular inducido por cisplatino.

Targeting ROCK1 in diabetic kidney disease: Unraveling mesangial fibrosis mechanisms and introducing myricetin as a novel antagonist.

Diabetic kidney disease (DKD) stands as a pressing health challenge, with mesangial cell fibrosis identified as a pivotal hallmark leading to glomerular sclerosis. Gaining a deeper grasp on the molecular dynamics behind this can potentially introduce groundbreaking therapeutic avenues. Recent revelations from studies on ROCK1-deficient mice, which displayed resilience against high-fat diet (HFD)-induced glomerulosclerosis and mitochondrial fragmentation, spurred our hypothesis regarding ROCK1's potential role in mesangial cell fibrosis. Subsequent rigorous experiments corroborated our theory, highlighting the critical role of ROCK1 in orchestrating mesangial cell proliferation and fibrosis, especially in high-glucose settings. Mechanistically, ROCK1 inhibition led to a notable hindrance in the high-glucose-triggered MAPK signaling pathway, particularly emphasizing the ROCK1/ERK/P38 axis. To translate this understanding into potential therapeutic interventions, we embarked on a comprehensive drug screening journey. Leveraging molecular modeling techniques, Myricetin surfaced as an efficacious inhibitor of ROCK1. Dose-dependent in vitro assays substantiated Myricetin's prowess in curtailing mesangial cell proliferation and fibrosis via ROCK1/ERK/P38 pathway. In vivo verifications paralleled these findings, with Myricetin treatment resulting in significant renal function enhancements and diminished DKD pathological markers, all pivoted around the ROCK1/ERK/P38 nexus. These findings not only deepen our comprehension of DKD molecular underpinnings but also elevate ROCK1 to the pedestal of a promising therapeutic beacon. Concurrently, Myricetin is spotlighted as a potent natural contender, heralding a new era in DKD therapeutic design.

Myricetin, a natural inhibitor of CD147, increases sensitivity of cisplatin in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological tumor, but it currently lacks effective therapeutic targets. CD147, which is overexpressed in OC, plays a crucial role in promoting malignant progression and is associated with poor prognosis in patients. Therefore, CD147 has been identified as a potential therapeutic target. However, there is a limited amount of research on the development of CD147 inhibitors. METHODS: Surface plasmon resonance (SPR) assay and virtual molecular docking analysis were performed to identify potential natural compounds targeting CD147. The anti­tumor effects of myricetin were evaluated using various assays, including CCK8, Alkaline comet, immunofluorescence and xenograft mouse models. The underlying mechanism was investigated through western blot analysis and lentivirus short hairpin RNA (LV-shRNA) transfection. RESULTS: Myricetin, a flavonoid commonly found in plants, was discovered to be a potent inhibitor of CD147. Our findings demonstrated that myricetin exhibited a strong affinity for CD147 and down-regulated the protein level of CD147 by facilitating its proteasome-dependent degradation. Additionally, we observed synergistic antitumor effects of myricetin and cisplatin both in vivo and in vitro. Mechanistically, myricetin suppressed the expression of FOXM1 and its downstream DNA damage response (DDR) genes E×O1and BRIP1, thereby enhancing the DDR induced by cisplatin. CONCLUSION: Our data demonstrate that myricetin, a natural inhibitor of CD147, may have clinical utility in the treatment of OC due to its ability to increase genomic toxicity when combined with cisplatin.

Myricetin-based fluorescence probes with AIE and ESIPT properties for detection of hydrazine in the environment and fingerprinting.

BACKGROUND: Hydrazine (N2H4) is a highly toxic and versatile chemical raw material, which poses a serious threat to the environment and human health when used in large quantities. However, the traditional methods for the detection of N2H4 have the disadvantages of time-consuming, complicated operation and expensive instruments. In contrast, fluorescence probes have many advantages, such as simple operation, high sensitivity, good selectivity, and fast response time. Therefore, there is an urgent need for a fluorescence probe that can rapidly and accurately detect the presence of N2H4 and monitor the changes in its concentration. RESULTS: For this purpose, we designed and synthesized a series of myricetin fluorescence probes 3-(substituent group)-5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxy. phenyl)-4H-chromen-4-one (Myr-R) for N2H4 detection. In the presence of N2H4, the probe 5,7-dimethoxy-3-(2,3,4,5,6-pentafluorobenzoate)-2-(3,4,5-trimethoxyphen-yl). -4H-chr-omen-4-one (Myr-3) shows significant fluorescence changes, double emission properties and a large Stokes shift (183 nm), and exhibits high selectivity and sensitivity to N2H4 (The detection limit is 93 nM). Importantly, the qualitative and quantitative analysis of N2H4 in water, soil, and air can be accomplished using fluorescence, smartphone, and UV lamps coupled with Myr-3. In addition, Myr-3 can be used for monitoring and imaging intracellular N2H4. Meanwhile, the fluorophore 3-hydroxy-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-benzopyran-4-one (Myr-Me) was applied to fingerprinting of different substrate materials due to the fact that it exhibits strong yellow fluorescence emission in the solid state and shows excellent contrast and high resolution. SIGNIFICANCE: The probe Myr-3 is not only able to rapidly detect N2H4 in complex environments, but also can be used for imaging intracellular N2H4. In addition, the fluorophore Myr-Me can be used as an effective imaging agent for visual fingerprinting. These properties enable the probe Myr-3 and the fluorophore Myr-Me for a wide range of potential applications in related fields.

Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a heterogeneous tumor with a poor prognosis and high metastatic potential, resulting in poor clinical outcomes, necessitating investigation to devise effective therapeutic strategies. Multiple studies have substantiated the anti-cancer properties of the naturally occurring flavonoid "Myricetin" in various malignancies. However, the therapeutic application of Myricetin is impeded by its poor water solubility and low oral bioavailability. To overcome this limitation, we aimed to develop nanoemulsion of Myricetin (Myr-NE) and evaluate its advantage over Myricetin alone in TNBC cells. The nanoemulsion was formulated using Capryol 90 (oil), Tween 20 (surfactant), and Transcutol HP (co-surfactant). The optimized nano-formulation underwent an evaluation to determine its size, zeta potential, morphology, stability, drug encapsulation efficiency, and in vitro release properties. The anti-cancer activity of Myr-NE was further studied to examine its distinct impact on intracellular drug uptake, cell-viability, anti-tumor signaling, oxidative stress, clonogenicity, and cell death, compared with Myricetin alone in MDA-MB-231 (TNBC) cells. The in vitro drug release and intracellular drug uptake of Myricetin was significantly increased in Myr-NE formulation as compared to Myricetin alone. Moreover, Myr-NE exhibited significant inhibition of cell proliferation, clonogenicity, and increased apoptosis with ~ 2.5-fold lower IC50 as compared to Myricetin. Mechanistic investigation revealed that nanoemulsion augmented the anti-cancer efficacy of Myricetin, most likely by inhibiting the PI3K/AKT/mTOR pathway, eventually leading to enhanced cell death in TNBC cells. The study provides substantial experimental evidence to support the notion that the Myr-NE formulation has the potential to be an effective therapeutic drug for TNBC treatment.

Flavonoid Metabolites in Serum and Urine after the Ingestion of Selected Tropical Fruits.

The serum concentration and urinary excretion of flavonoids after the ingestion of guava, pineapple, and pomelo were determined using liquid chromatography-mass spectroscopy (LC-MS/MS). Each group of healthy volunteers was given 200 g of fresh fruit after overnight fasting and a 24-h flavonoid-free diet. The results demonstrate that only the glucuronic-conjugated metabolites of luteolin, quercetin, kaempferol, and myricetin were detected after fruit ingestion. The metabolites were first detected after 2 h, with the time to maximum concentration (Tmax) at 6 h. The most abundant metabolites for guava, pineapple, and pomelo were the glucuronide metabolites of quercetin (AUC0-8 5.4 ± 1.3 µg·h/mL), kaempferol (AUC0-8 9.9 ± 2.3 µg·h/mL), and luteolin (AUC0-8 6.4 ± 1.1 µg·h/mL), respectively. The flavonoids found in the 24-h urinary excretions were glucuronic- and mainly sulfate-conjugated metabolites. Quercetin metabolites were the most abundant after guava and pineapple ingestion, accounting for 900 and 700 µg, respectively. Luteolin metabolites were the most abundant after pomelo ingestion, accounting for 450 µg. The serum and urinary metabolite profiles suggested that guava and pineapple are good sources of quercetin, pineapple is a good source of kaempferol, and pomelo is a good source of luteolin. The study of flavonoid profiles may provide information for the selection of fruits as functional foods for their health benefits to help with various health conditions.

Myricetin derivatives containing the benzoxazinone moiety discovered as potential anti-tobacco mosaic virus agents.

A series of myricetin derivatives containing benzoxazinone were designed and synthesized. The structures of all compounds were characterized by NMR and HRMS. The structure of Y4 had been confirmed by single-crystal X-ray diffraction analysis. The test results of EC50 values of tobacco mosaic virus (TMV) suggested that Y8 had the best curative and protective effects, with EC50 values of 236.8, 206.0 µg/mL, respectively, which were higher than that of ningnanmycin (372.4, 360.6 µg/mL). Microscale thermophoresis (MST) experiments demonstrated that Y8 possessed a strong binding affinity for tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (Kd) value of 0.045 µM, which was superior to the ningnanmycin (0.700 µM). The findings of molecular docking studies revealed that Y8 interacted with multiple amino acid residues of TMV-CP through the formation of non-covalent bonds, which had an effect on the self-assembly of TMV particles. The malondialdehyde (MDA) and superoxide dismutase assay (SOD) content assays also fully verified that Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA content and increasing SOD content. In summary, myricetin derivatives containing benzoxazinone could be considered to further research and development as novel antiviral agents.