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This study compared the effectiveness of various cleaning approaches, including spray rinsing, repreparing with diamond burs, and using phosphoric acid or sodium hypochlorite alone or with polyphenols (resveratrol or myricetin), in removing blood contamination from the dentine after adhesive light-curing. The contact angles of the treated surfaces were measured and scanning electron microscopy/ energy dispersive X-ray spectroscopy observation was performed. The bond strength and nanoleakage were assessed, and in situ zymography was performed before and after aging. Interactions between matrix metalloproteinase (MMP)−9 and polyphenols were evaluated using molecular dynamics and rhMMP-9 inhibition analyses. The destruction of sodium hypochlorite on collagen and the resistance of polyphenols-treated dentine collagen to enzymolysis were evaluated using the hydroxyproline (HYP) assay. The effect of polyphenols on dentine collagen crosslinking was assessed by Fourier Transform Infrared Spectroscopy. The repreparation group had the lowest contact angle compared to the other groups. The spray rinsing group had the lowest bond strength and highest amounts of nanoleakage. Cleaning with phosphoric acid or sodium hypochlorite alone removed the blood contaminants and parts of the adhesive; moreover, applying polyphenols further improved the bond strength and decreased nanoleakage and MMP activity after aging. Both polyphenols inhibited rhMMP-9 activity and promoted collagen crosslinking. Sodium hypochlorite showed the maximum HYP release when used alone, which was decreased after adding polyphenols. Phosphoric acid or sodium hypochlorite cleaning can remove blood contamination from the dentine surface after adhesive curing, and the addition of polyphenols can improve the durability of dentine bonding. [Display omitted] • Phosphoric acid or sodium hypochlorite cleaning removed blood and part of the cured adhesive. • Phosphoric acid or sodium hypochlorite cleaning restored dentine bonding influenced by blood contamination. • Resveratrol and myricetin improved the resistance of collagen to exogenous enzymes. • Resveratrol and myricetin inhibited MMP activity and promoted collagen cross-linking. • Resveratrol and myricetin can contribute to the durability of the dentine bonding. [ABSTRACT FROM AUTHOR]

This study developed a structured fruit cube (FC) snack using only natural ingredients, specifically red grape and apple, without hydrocolloids and sucrose. After development, physicochemical characterization and analysis of phenolic compounds (PCs), including anthocyanins, flavonols, and hydroxycinnamic acid derivatives, using HPLC-DAD-ESI-MS/MS, were conducted. Sensory quality was also assessed through an acceptance and sensory profile analysis using the rate-all-that-apply methodology. The results showed that the FC had physicochemical characteristics similar to other structured fruits that use hydrocolloids. Additionally, they presented a complex composition of PCs, predominantly including anthocyanins derived from malvidin (tri-substituted methoxylated anthocyanins), notably cumarylated ones. Flavonols compounds comprised the 3-glucoside series of myricetin, quercetin, laricitrin, kaempferol, isorhamnetin, and syringetin; the 3-galactoside series of myricetin and quercetin; and the 3-glucuronic acid series of myricetin and quercitin, along with rutin. The presence of caftaric acid, coutaric acid, fertaric acid, and p-coumaroyl-glucose was also detected, alongside caffeic acid-O-glucoside 1, caffeic acid-O-glucoside 2, chlorogenic acid, 4-O-p-coumaroylquinic acid, and dicaffeoylquinic acid. In conclusion, the selection of natural ingredients was technologically suitable for obtaining an FC. Despite using conventional drying at 60 °C, the product showed notable concentrations of PCs and also achieved great sensory acceptance. [ABSTRACT FROM AUTHOR]

Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin‐3′‐O‐sulfate (M3′S), AMP, and ampelopsin‐4′‐O‐sulfate (A4′S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion‐transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3′S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3′S, AMP, and A4′S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3′S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3′S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR‐containing dietary supplements may affect the OATP‐mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3′S. [ABSTRACT FROM AUTHOR]

Background: Myricetin, a flavonoid, has anti-inflammation effects and can improve pancreatic β cells dysfunction. However, the role of myricetin in severe acute pancreatitis (SAP) and the precise mechanism remain unclear. Objectives: This study aimed to investigate how myricetin affects pancreatic damage induced by SAP. Results: Myricetin substantially reduced the expression of lipase and amylase, and ameliorated pancreatic damage induced by SAP. Moreover, myricetin inhibited the release of several inflammatory relevant cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10, alleviated apoptosis of pancreatic alveolar cells, and ameliorated microcirculatory dysfunction in SAP rats. Furthermore, myricetin inhibited the acetylation of forkhead box protein O1(FOXO1) and the phosphorylation of NF-kB. Conclusion: Myricetin improves SAP-induced pancreatic injury through suppressing microcirculation dysfunction, overactive inflammatory response, and cell apoptosis. In addition, myricetin deregulates acetylated FOXO1 and phosphorylated nuclear factor kappa B (NF-kB), which may be the potential mechanism for SAP alleviation. [ABSTRACT FROM AUTHOR]

The hydrogel platform with intelligent drug delivery system possesses great potential in the treatment of diabetic wounds. Nevertheless, the intelligent elimination of reactive oxygen species (ROS) remains a formidable challenge in facilitating diabetic wound healing. Herein, a hydrogel platform with triple‐triggered on‐demand release is constructed to intelligently scavenge ROS and modulate the wound microenvironment to accelerate diabetic wound healing through the release of antioxidative factors. Specifically, the gelatin (Gel) is modified with phenylboronic acid (PBA) to obtain a glucose‐sensitive Gel derivative (Gel‐BA), which is mixed with oxidized dextran (ODex) and the strong antioxidant myricetin (MY) to swiftly generate a hydrogel platform (OGM). Significantly, the smart release of MY from the hybrid hydrogel under inflammatory conditions intelligently eliminates ROS, effectively alleviating oxidative stress and promoting angiogenic reprogramming of the wound immune microenvironments by activating the Nrf2 pathway. In summary, in vitro and in vivo studies reveal that the OGM hydrogel platform significantly promotes cell proliferation, migration, and tube formation and greatly accelerates diabetic wound healing, offering a local‐specific triple‐response drug release strategy for the treatment of diabetic wound management. [ABSTRACT FROM AUTHOR]

Flavonols got particular attention in the last few years. We hypothesized that the seasonal changes in the availability of their sources do not impact the general flavonols intake. Forty volunteers were enrolled in the study. The 3-day food interviews were performed in 3-month intervals for one year and compared with the FFQ dedicated to the yearlong assessment of flavonols intake. The analysis did not show significant differences for quercetin, kaempferol, isorhamnetin, and total flavonols throughout the year. Significant differences were observed only for myricetin (P = 0.003). At the same time, the detailed analysis of the categories of the consumed products showed significant differences in the seasonal structure of the intakes of fruits (P = 0.01), vegetables (P = 0.046), herbs and spices (P = 0.002), and tea and coffee (P = 0.01). The analysis of the correlation between the results of the one-year follow-up and the results of the FFQ showed significant correlations for total flavonols (R = 0.55; P = 0.001), kaempferol (R = 0.66; P < 0.001), quercetin (R = 0.48; P = 0.002), isorhamnetin (R = 0.41; P = 0.01), and myricetin (R = 0.49; P = 0.001) intakes. This study showed that despite the fluctuations in the selected product intake, the overall intake of quercetin, kaempferol, isorhamnetin, and total flavonols did not show significant differences throughout the year. The analysis showed good agreement between FFQ dedicated to the yearlong assessment of the flavonols intake and multiple food interviews, which proves the validity of the FFQ. [ABSTRACT FROM AUTHOR]

The molecular and crystal structures of myricetin have been studied using density functional theory. The geometry parameters are calculated based on the optimized molecular structure, and the thermodynamic properties "heat capacity (p m C,), enthalpy (m H) and entropy (m H)" are performed using our selfprogrammed programme, the calculated results are consistent with literature reports. Crystal structures were predicted using the Dreiding force field and refined by DFT-GGA-RPBE method. The crystal form tends to crystalline in P-1 space group. The large calculated band gap (Eg) of the crystal proves it is stable, which is consistent with the conclusion from gas phase. The conduction band (LUCO) is mainly contributed from the p state of C atom and valence band (HOCO) from the p state of O atom. [ABSTRACT FROM AUTHOR]

Objective: Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date. Methods: Computational docking and molecular dynamics simulation studies were performed to assess myricetin's potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin. Results: Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo. Conclusion: In summary, our findings underscore myricetin's potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway. [ABSTRACT FROM AUTHOR]

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The aim of this study was to evaluate the impact of ethanol extracts from sea buckthorn and Cornelian cherry fruits and leaves on physiology of gastrointestinal tract cells. We used three cell lines relevant to the types of cells, which are exposed to bioactive compounds after oral administration, namely intestinal absorptive cells (Caco-2/HT-29 MTX model), hepatocytes (HepG2 cells) and immunocompetent cells (RAW 264.7 and P388D1 monocytes). The contents of antioxidant and bioactive polyphenols, such as cinnamic, caffeic and p-coumaric acids, rutin, myricetin, resveratrol, quercetin, apigenin and kaempferol, were assessed in the extracts using HPLC chromatography. The application of the extracts to Caco-2/HT-29-MTX cultures increased enterocyte differentiation markers (alkaline phosphatase and villin1 level) and goblet cell markers (mucins) over a fortnight. The extracts reduced lipid droplet size in hepatocytes challenged with hyperglycaemic glucose concentration, insulin and palmitate. Sea buckthorn leaf, fruit and Cornelian cherry leaf extracts blocked oxidative burst in the PMA-stimulated monocytes, while the sea buckthorn leaf and Cornelian cherry fruit extracts downregulated lipopolysaccharide-induced NO and IL-1β, respectively. The results indicate that the tested extracts modulate the behaviour of cells in the gastrointestinal tract in a beneficial way, especially regarding lipid accumulation and innate immunity actions. [ABSTRACT FROM AUTHOR]

The effect of various flavonoids against oxidative stress and inflammation caused by lead exposure has been investigated. However, the protective effects of myricetin (MYC) and fisetin (FST), which are known to have potent antioxidant properties, against nephrotoxicity caused by exposure to lead acetate (LA), the water-soluble form of lead, have not been investigated. Our study investigated the protective role of these flavonoids against LA intoxication-induced nephrotoxicity. In our study, 42 male rats were used. The rats were randomly selected and divided into 6 groups. These groups were: control, LA (100 g/kg), LA + MYC (100 mg/kg), LA + MYC (200 mg/kg), LA + FST (100 mg/kg) and LA + FST (200 mg/kg). All chemicals were administered daily by gavage for 28 days. According to the experimental protocol, the animals were sacrificed and their kidney tissues were isolated. Serum biochemical parameters, histological examinations, levels of several trace elements, oxidative stress and inflammatory parameters at both biochemical and molecular levels in kidney tissues were examined. After LA administration, tissue lead levels increased and zinc levels decreased. This situation was reversed by MYC and FST treatment. Oxidative stress and inflammatory response were increased in the kidney tissue of LA-treated rats and renal function was impaired. It was observed that both doses of MYC and high dose of FST could prevent nephrotoxicity. Oral administration of both doses of MYC and high dose FST ameliorated the changes in biochemical, oxidative and inflammatory parameters. Restoration of normal renal tissue architecture was also demonstrated by histological studies. MYC and FST were found to have promising biological activity against LA-induced nephrotoxicity, acting by attenuating inflammation and oxidative stress and improving antioxidant status. [ABSTRACT FROM AUTHOR]

Background: Lannea egregia Engl. & K. Krause (family: Anacardiaceae) is a well-known medicinal plant in Nigeria whose various parts have been shown to elicit several biological activities. This study specifically explored the leaf of L. egregia for potential cytotoxic compounds. Methods: n-Hexane, dichloromethane and methanolic extracts of the leaf were prepared using the Soxhlet apparatus and concentrated using the rotary evaporator. Compounds were isolated by reversed-phase preparative high-performance liquid chromatography, and the structures were determined by spectroscopic means. The methanolic extract and the isolated compounds were screened for cytotoxicity against HeLa and MCF-7 cancer cell lines, using the MTT assay. Results: Three flavonoids, myricetin (1), myricetin 3-O-α-L-rhamnoside (2) and quercetin 3-O-α-L-rhamnoside (3), were isolated from the methanolic extract of the leaf of L. egregia. The methanolic extract and compound 3 showed the most potent inhibition profiles against the cells, with IC50 values (Mean ± SEM) of 45.3 ± 1.5 µg/mL and 57.5 ± 0.4 µg/mL for the methanolic extract, and 36.5 ± 2.0 µM and 57.9 ± 10.1 µM for compound 3, against HeLa and MCF-7 cells, respectively. Conclusion: Conclusion: This work shows that L. egregia leaf is moderately cytotoxic, and rich in flavonoids, and the cytotoxicity of the extract is, at least partially, due to the presence of cytotoxic flavonoids. This is the first report on characterized isolated compounds from the leaf of L. egregia and the occurrence of flavonols in the leaf.

Objective Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date. Methods Computational docking and molecular dynamics simulation studies were performed to assess myricetin’s potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin. Results Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo. Conclusion In summary, our findings underscore myricetin’s potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway.

In order to clarify the effects of myricetin on the physicochemical properties of corn starch during digestion and absorption in the gastrointestinal tract, in vitro simulation of corn starch digestion experiment was carried out. It was found that myricetin could significantly inhibit the digestion of corn starch and thus affect the body's blood sugar content. The addition of myricetin (1.7~15.3 mg/mL) reduced the rapidly digestible starch (RDS) content of corn from 22.72% to 19.35% and increased the resistant starch (RS) content of corn from 18.11% to 39.25%. Through static rheology, differential scanning calorimetry (DSC), X-ray diffraction (XRD), infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) experiments, it was found that myricetin bound to corn starch through non-covalent interactions and affected its digestibility by decreasing its thermal stability and disrupting the original crystalline structure of corn starch, which deloyed the digestion and absorption of corn starch. This study can provide a theoretical and experimental basis for the use of myricetin as a hypoglycemic factor.

Background: Arsenic (AS) is a toxic heavy metal that poses a significant concern for both animal and human health. Aim: The study investigated the ameliorative effect of myricetin (MRC) against arsenic-induced immune dysfunction, oxidative stress, hematological changes, hepatic and renal injuries, and inflammatory gene expression in rats. Methods: Rats were divided into 4 groups: the control group (CON) received orally administered distilled water (1 ml/rat), and the ARS group received 10 mg/kg orally, the MRC group received 5 mg of MRC/kg orally, and the co-treated group (ARS+MRC) received 10 mg/kg of ARS and 5 mg/kg b.w. of MRC orally. Results: The results showed that co-treatment of ARS-exposed rats with MRC significantly corrected erythrocyte parameters (except MCV) and leukocyte parameters (except basophils; p [Open Vet J 2024; 14(7.000): 1677-1688]

Abstract Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson’s disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.

A method for quantitative determination of myricitrin in common myrtle (Myrtus communis L.) leaves using high-performance liquid chromatograph (HPLC) was developed. The content of the dominant flavonoid myricitrin (myricetin 3-O-α-L-rhamnopyranoside) in common myrtle leaves varied from 0.98 ± 0.02% to 1.51 ± 0.07%. The error of a single determination and the average error of the myricitrin content determination in common myrtle leaves were ±15.81% and ±4.77%, respectively, with confidence probability 95%. [ABSTRACT FROM AUTHOR]

Urolithiasis or nephrolithiasis is a condition of kidney stone formation and is considered a painful disease of the urinary tract system. In this work, we planned to discover the therapeutic roles of myricetin on the ethylene glycol (EG)-induced nephrolithiasis in rats. The experimental rats were treated with 0.75% of EG through drinking water for 4 weeks to initiate the nephrolithiasis and subsequently treated with 25 and 50 mg/kg of myricetin. The body weight and urine volume were measured regularly. After the sacrification of rats, the samples were collected, and serum and urinary biomarkers such as creatinine, urea, Ca2 + ion, and BUN, OPN, oxalate, and citrate levels were determined using assay kits. These biomarkers, the MDA level and CAT, SOD, and GPx activities, were assessed in the kidney tissue homogenates. The IL-6, IL-1β, and TNF-α levels were also quantified using respective kits. The histopathological analysis was done on the kidney tissues. Myricetin treatment did not show major changes in the body weight and kidney weight in the EG-induced rats. The treatment with 25 and 50 mg/kg of myricetin considerably reduced the urea, creatinine, BUN, Ca2 + ion, and oxalate and increased the citrate content in serum and urine samples of EG-induced rats. Further, myricetin depleted the inflammatory cytokines and MDA levels and elevated the CAT, SOD, and GPx activities in the renal tissues. The activities of ALT, AST, ALP, GGT, and LDH were also reduced by the myricetin. Furthermore, the myricetin upheld the histoarchitecture of the kidneys. The outcomes of this investigation propose that myricetin is effective in EG-induced urolithiasis probably because of its antioxidant, anti-inflammatory, and renoprotective activities. In addition, further studies are still required to verify the precise therapeutic mechanism of myricetin. [ABSTRACT FROM AUTHOR]

This document is a compilation of scientific articles that discuss the role of gut microbiota in human metabolic health and disease. The articles explore topics such as the impact of gut microbiota on glucose control, energy metabolism, inflammation, and insulin resistance in conditions like type 2 diabetes and prediabetes. They also examine the influence of dietary fiber, short-chain fatty acids, and specific bacteria on gut homeostasis and immune responses. The articles provide insights into the complex interactions between the gut microbiome and host metabolism, suggesting the potential for microbiota-based interventions in the prevention and treatment of metabolic diseases. [Extracted from the article]

Myricetin, a natural flavonoid found in various foods, was investigated for its antiviral effect against transmissible gastroenteritis virus (TGEV). This a-coronavirus causes significant economic losses in the global swine industry. The study focused on the papain-like protease (PLpro), which plays a crucial role in coronavirus immune evasion by mediating deubiquitination. Targeting PLpro could potentially disrupt viral replication and enhance antiviral responses. The results demonstrated that myricetin effectively inhibited TGEV-induced cytopathic effects in a dose-dependent manner, with an EC50 value of 31.19 mM. Myricetin significantly reduced TGEV viral load within 48 h after an 8-h co-incubation period. Further investigations revealed that myricetin at a concentration of 100 mM directly inactivated TGEV and suppressed its intracellular replication stage. Moreover, pretreatment with 100 mM myricetin conferred a protective effect on PK-15 cells against TGEV infection. Myricetin competitively inhibited PLpro with an IC50 value of 6.563 mM. Molecular docking experiments show that myricetin binds to the Cys102 residue of PLpro through conventional hydrogen bonds, Pi-sulfur, and Pi-alkyl interactions. This binding was confirmed through site-directed mutagenesis experiments, indicating myricetin as a potential candidate for preventing and treating TGEV infection. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD. [ABSTRACT FROM AUTHOR]

Background: Arsenic (ARS) is a toxic heavy metal that poses a significant concern for both animal and human health. Aim: The study investigated the ameliorative effect of myricetin (MRC) against arsenic-induced immune dysfunction, oxidative stress, hematological changes, hepatic and renal injuries, and inflammatory gene expression in rats. Methods: Rats were divided into 4 groups: the control group (CON) received orally administered distilled water (1 ml/ rat), and the ARS group received 10 mg/kg orally, the MRC group received 5 mg of MRC/kg orally, and the co-treated group (ARS+MRC) received 10 mg/kg of ARS and 5 mg/kg b.w. of MRC orally. Results: The results showed that co-treatment of ARS-exposed rats with MRC significantly corrected erythrocyte parameters (except MCV) and leukocyte parameters (except basophils; p < 0.05). Furthermore, the ARS group significantly reduced total proteins and globulins while significantly increasing liver functions and uric acid levels (p < 0.05). Co-administration with MRC significantly mitigated the heart indices (gamma-glutamyl transferase, creatine phosphokinase, CK, lactate dehydrogenase) and lipid dysfunction caused by ARS exposure (p < 0.05). In ARS-exposed rats, there was a significant reduction in antioxidant enzymes and immunoglobulins (IgG and IgM), as well as significantly increased oxidative stress (p < 0.05). The MRC treatment effectively restored the redox status and immune variables that were disrupted by ARS exposure. Serum levels of nitric acid and lysosome were significantly lower, while levels of IL-4, TNF-Á, and IFN-γ were higher in the ARS group compared to the other groups (p < 0.05). Immunohistopathology revealed that the expression of Cox2 in kidney and liver tissues varied from mild to moderate in the ARS+MRC group. Furthermore, the ARS-induced upregulation of mRNA levels of inflammatory genes such as IFN-γ, TNF-α, IL-10, and IL-6 in hepatic tissues and MRC significantly attenuated this elevation. These findings suggest that ARS has detrimental effects on blood hematology and health, triggering specific inflammatory genes and indicating the genotoxicity of ARS. However, co-treatment with MYC can mitigate these negative effects. Conclusion: MRC exhibits a significant protective effect against ARS due to its anti-inflammatory and antioxidant properties. [ABSTRACT FROM AUTHOR]

Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. 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. 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. MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR. [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used chemotherapy drug for the treatment of various cancers. However, although cisplatin is effective in targeting cancer cells, it has severe side effects including skeletal muscle atrophy. In this study, we aimed to characterize the role of Dihydromyricetin in cisplatin-induced muscle atrophy in mice. 5-week-old male C57BL/6 mice were treated with Dihydromyricetin for 14 days orally followed by in intraperitoneally cisplatin administration for 6 days. Gastrocnemius muscles were isolated for the following experiments. Antioxidative stress were determined by peroxidative product malondialdehyde (MDA) and antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Quadriceps muscle mass and grip strength were significantly restored by Dihydromyricetin in a dose-dependent manner. Moreover, muscle fibers were improved in Dihydromyricetin treated group. Excessive skeletal muscle E3 ubiquitin-protein ligases in cisplatin group were significantly repressed by Dihydromyricetin treatment. Dihydromyricetin significantly reduced oxidative stress induced by cisplatin by decreasing MDA level and restored SOD and GPx activities. In addition, ferroptosis was significantly reduced by Dihydromyricetin characterized by reduced iron level and ferritin heavy chain 1 and improved Gpx4 level. The present study demonstrated that Dihydromyricetin attenuated cisplatin-induced muscle atrophy by reducing skeletal muscle E3 ubiquitin-protein ligases, oxidative stress, and ferroptosis. [ABSTRACT FROM AUTHOR]

Myricetin has been reported to have a wide variety of beneficial physiological functions. The present study investigated the antihyperlipidaemic activity of myricetin against hyperlipidaemia of high-fat diet-fed obese rats. The four-week antihyperlipidaemic activity was assayed by giving different doses of myricetin to hyperlipidaemic rats. Results showed that myricetin could reduce the harm caused by oxidative stress, decrease thiobarbituric acid reactive substances value, and decrease total cholesterol and triacylglycerol levels of hyperlipidaemic rats. Quantitative analysis of gene expression showed that myricetin's lipid-lowering activity can be activated by downregulating gene expression of fatty acid synthase (FAS) and peroxisome proliferator-activated receptor-γ (PPARγ) with upregulation of hormone-sensitive lipase (HSL) mRNA level. Thus, myricetin had significant health benefits and could be explored as a potentially promising dietary supplement for treating hyperlipidaemia. [ABSTRACT FROM AUTHOR]

Myricetin can be found in the traditional Chinese medicinal plant, Myrica rubra. Myricetin is a flavonoid that is present in many vegetables, fruits, and plants and is considered to have strong antioxidant properties as well as a wide range of therapeutic applications. Growing interest has been piqued by its classification as a polyphenolic molecule because of its potential therapeutic benefits in both the prevention and management of numerous medical conditions. To clarify myricetin's traditional medical uses, modern research has investigated various pharmacological effects such as antioxidant, anticancer, anti‐inflammation, antiviral, antidiabetic, immunomodulation, and antineurodegenerative effects. Myricetin shows promise as a nutritional flavonol that could be beneficial in the prevention and mitigation of prevalent health conditions like diabetes, cognitive decline, and various types of cancer in humans. The findings included in this study indicate that myricetin has a great deal of promise for application in the formulation of medicinal products and nutritional supplements since it affects several enzyme activities and alters inflammatory markers. However, comprehensive preclinical studies and research studies are necessary to lay the groundwork for assessing myricetin's possible effectiveness in treating these long‐term ailments. This review summarizes both in vivo and in vitro studies investigating myricetin's possible interactions through the nuclear factor‐E2‐related factor 2 (Nrf2) as well as PI3K (phosphatidylinositol 3‐kinase)/AKT (protein kinase B) signaling pathways in an attempt to clarify the compound's possible clinical applicability across a range of disorders. [ABSTRACT FROM AUTHOR]

Myricetin is a natural flavonoid with anti-cancer and anti-inflammatory effects, but its mechanism for treating lung adenocarcinoma (LUAD) remains unclearly. Therefore, bioinformatics, in silico and in vitro experiments were employed to elucidate this issue in this study. The core targets of myricetin against LUAD were screened by PharmaMapper (v2017), Assistant for Clinical Bioinformatics, STRING (v11.5) and Cytoscape (v3.8.1). Using Kaplan–Meier Plotter (v2022.04.20), UALCAN (v2021.12.13) and GEPIA (v2.0) databases, the correlation between core genes and the prognosis of LUAD patients were analyzed, and the expression levels of core genes were verified. In silico studies were used to analyze the binding energies and sites of myricetin with core genes. The effects of myricetin on H1975 cells were explored through thiazolyl blue (MTT), cell migration, colony formation and western blot assays. A total of 72 potential targets of myricetin against LUAD were identified through bioinformatics. Among the four core targets obtained by multiple networks and in silico assays, the up-regulated MMP9 (HR = 1.14 (1–1.29), logrank P = 0.046) and down-regulated PIK3R1 (HR = 0.58 (0.51–0.66), logrank P < 1E-16) were positively correlated with poor survival outcomes in LUAD patients. In vitro experiments demonstrated that myricetin inhibited the proliferation and migration of H1975 cells, promoting their apoptosis. Myricetin inhibits the proliferation of H1975 cells and induces cell apoptosis through its influence on the expression levels of MMP1, MMP3, MMP9, and PIK3R1 and regulating the multiple pathways these genes participate in. Both MMP9 and PIK3R1 are potential biomarkers for LUAD. [ABSTRACT FROM AUTHOR]

Abstract Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin‐3′‐O‐sulfate (M3′S), AMP, and ampelopsin‐4′‐O‐sulfate (A4′S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion‐transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3′S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3′S, AMP, and A4′S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3′S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3′S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR‐containing dietary supplements may affect the OATP‐mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3′S.

Background: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 μg/mL. Time–kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin. [ABSTRACT FROM AUTHOR]

The levels of different nutraceutical metabolites present in the jicama root were measured when subjecting the plant to induced biotic stress via infestation with Phyllophaga spp. (white grubs). The change in secondary metabolites on the stressed jicama roots (SJ), mostly antioxidants, was followed over 100, 140, and 180 days and compared against the non-infested control jicama (CJ). Our results show that infested (SJ) samples contained higher concentrations of tannins, flavonoids, and total phenols, measured using spectrophotometric methods, peaking at 140 days, and higher overall concentration of saponins. SJ samples showed higher DPPH inhibition, peaking at 100 days. Chlorogenic acid had the highest concentration among the phenolic compounds (7.47 mg g−1), followed by protocatechuic acid, both in SJ, which was possibly related to the lower observed concentrations of caffeic and ferulic acids. As for flavonoids, we observed a high concentration of rutin in CJ and a low concentration of pelargonidin and myricetin in SJ, possibly promoted via the dihydrokaempferol pathway. Taken together, these results show that Phyllophaga spp.-mediated biotic stress affects the concentrations of secondary metabolites in the different maturity stages in jicama, having an effect on its metabolic pathways, which presents an opportunity for the use of material such as agro-industrial waste. [ABSTRACT FROM AUTHOR]

α‐Tocopherol (α‐TOC) and myricetin (MYR) synergistically inhibit lipid oxidation in bulk oil but the mechanism underlying this effect is unknown. In this research, stripped soybean oil (SSO) was treated with α‐tocopherol (50 μM), myricetin (10–250 μM), and their combinations. Taxifolin (TAX) was also tested because it has structural similarities to myricetin but with a higher redox potential. α‐Tocopherol: myricetin ratios of 5:1, 2:1, 1:1, 1:2, and 1:5 resulted in extended lag phases ranging from 16 to 99 days, with lag phase increasing with increasing myricetin concentrations. Synergism between α‐tocopherol and myricetin was also observed in phospholipid‐containing bulk oils both in the absence and presence of reverse micelles, although the reverse micelles shortened the lag phases. Myricetin (redox potential = 360 mV) delayed the oxidation of α‐tocopherol (redox potential = 500 mV) whereas taxifolin (redox potential = 500 mV) did not. Both myricetin and taxifolin were able to chelate iron as determined by UV–VIS spectroscopy. These results suggested that the lower redox potential of myricetin allowed it to produce synergistic antioxidant activity potentially by regenerating oxidized α‐tocopherol and through its ability to decrease oxidation by metal chelation. [ABSTRACT FROM AUTHOR]

Pepper processing waste has the potential to be used as a substrate in the process of anaerobic digestion, but because of its high polyphenol content, certain limitations are expected. During the determination of the biodegradability of pepper samples, a biogas potential of 687 L/kg DM was observed, as well as a biomethane potential of 401 L/kg DM. While both the testing of biodegradability and the process in the pilot scale progressed, it was observed that total polyphenol content in both cases decreased. Also, as far as individual polyphenols during the process in the pilot scale are concerned, it can be observed that at the end of the process no procyanidin A2, epicatechin, myricetin, and quercetin were detected. The observed concentration of the ferulic acid on the last day of the process was 0.09 µg/g. Finally, it can be concluded that the presence of polyphenols did not significantly affect the biogas potential of pepper waste. Due to its relatively stable biogas production, as far as biogas production on the pilot scale is concerned, it can be concluded that pepper processing waste has the potential to be used as a substrate for biogas production. [ABSTRACT FROM AUTHOR]

In this study, a UHPLC-PDA method for the simultaneous identification of polyphenols and bitter acids (alpha, beta, and isoalpha) in beer was developed. The resulting chemical profiles were leveraged to distinguish the characteristics of four (IPA, Lager, Blanche, ALE) bergamot-flavored beers, produced on a pilot-scale plant. In a streamlined 29 min analysis, thirty polyphenols and fourteen bitter acids were successfully identified under optimized separation conditions. Validation, encompassing parameters such as LOD (from 0.028 ppm for isorhamnetin to 0.106 for narirutin), LOQ (from 0.077 ppm for naringenin to 0.355 for narirutin), R2 (always more than 0.9992), repeatability (from 0.67% for tangeretin to 6.38% for myricetin), and reproducibility (from 0.99% for sinensetin to 6% for naringin), was conducted for polyphenol quantification using constructed calibration curves with seven levels. Exploring polyphenolic components as potential discriminators among different beer styles, a total of thirty-two polyphenolic compounds were identified and quantified, including characteristic bergamot peel polyphenols like neoeriocitrin (from 7.85 ppm for CBS2 to 11.95 ppm in CBS1); naringin (from 4.56 ppm for CBS4 to 10.96 in CBS1), and neohesperidin (from 5.93 in CBS3 to 15.95 for CBS2). The multivariate analysis provided additional insights into variations among specific beer styles, revealing discrepancies in the presence or relative concentrations of specific compounds linked to brewing ingredients and processes. This research enhances the fingerprinting of the chemistry governing beer quality through a straightforward and cost-effective analytical approach. [ABSTRACT FROM AUTHOR]

Intervertebral disc (IVD) degeneration (IDD) is a prevalent musculoskeletal disorder. Nucleus pulposus cells (NPCs) play a significant role in the normal functioning of the IVD. Myricetin is an agent that exerts anti-inflammatory and antioxidant effects in various pathological conditions. Here, we investigated the ameliorative effects of myricetin on the IVD degeneration. NPCs were obtained from the IVD of rats, and were treated with myricetin (0, 5, 10, 15, 20 μM) for 24 h before 20 ng/mL IL-1β stimulation. RT-qPCR, western blotting, and ELISA were applied to evaluate the levels of inflammatory factors (iNOS, COX-2, TNF-α, IL-6, PGE2, and Nitrite) and extracellular matrix (ECM)-associated components (MMP13, ADAMTS-5, aggrecan, and collagen II) in NPCs. Activation status of related signaling pathways (NF-κB and Nrf2) was determined using western blotting and immunofluorescence staining. Experimental rat models of IDD were established using a needle puncture method. Myricetin (20 mg/kg) was administrated intraperitoneally, and the degeneration was evaluated using histopathological analysis. Myricetin treatment attenuated the IL-1β-induced production of inflammatory factors in NPCs. Downregulation of aggrecan and collagen II as well as upregulation of MMP-13 and ADAMTS-5 in NPCs caused by IL-1β was reversed by myricetin treatment. Mechanistically, myricetin blocked NF-κB signaling by activation of Nrf2 in IL-1β-stimulated NPCs. Moreover, inhibition of Nrf2 reversed the protective effects of myricetin in NPCs. The in vivo experiments showed that myricetin ameliorated the IDD progression in rats. The present work suggests that Nrf2 is involved in the pathogenesis of IDD and shows the protective effects as well as the underlying mechanism of myricetin on Nrf2 activation in NPCs. [ABSTRACT FROM AUTHOR]

The relationship between the chemical structures of six flavonoids and their abilities to inhibit the formation of polycyclic aromatic hydrocarbons (PAHs) in a heated meat model system was investigated. The PAH8 forming in samples was analyzed by using QuEChERS coupled GC-MS. Inhibitory effects of PAHs were myricetin (72.1%) > morin (55.7%) > quercetin (57.3%) > kaempferol (49.9%) > rutin (32.7%) > taxifolin (30.2%). The antioxidant activities of these flavonoids, assessed through (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity assay (DPPH), [2,2′-azinobis (3-ethylbenzothiazoline-6-sulphonic acid)] free radical scavenging activity assay (ABTS) and ferric ion reducing antioxidant power assay (FRAP) assays, exhibited a significant negative correlation with PAH reduction. Notably, myricetin that contained three hydroxyl groups on the B-ring, along with a 2,3-double bond in conjugation with a 4-keto moiety on the C-ring, demonstrated strong antioxidant properties and free radical scavenging abilities, which significantly contributed to their ability to inhibit PAH formation. However, rutin and taxifolin, substituted at the C-3 position of the C-ring, decreased the PAH inhibitory activity. The ABTS assay proved the most effective in demonstrating the correlation between flavonoid antioxidant properties and their capacity to inhibit PAH formation in heated meat model systems. Thus, the inhibition of PAHs can be achieved by dietary flavonoids according to their chemical structures. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of Key lime (Citrus aurantifolia L., F. Rutaceae) peels afforded six metabolites, known as methyl isolimonate acetate (1), limonin (2), luteolin (3), 3ˋ-hydroxygenkwanin (4), myricetin (5), and europetin (6). The structures of the isolated compounds were assigned by 1D NMR. In the case of limonin (2), further 1- and 2D NMR experiments were done to further confirm the structure of this most active metabolite. The antiplasmodial properties of the obtained compounds against the pathogenic NF54 strain of Plasmodium falciparum were assessed in vitro. According to antiplasmodial screening, only limonin (2), luteolin (3), and myricetin (5) were effective (IC50 values of 0.2, 3.4, and 5.9 µM, respectively). We explored the antiplasmodial potential of phytochemicals from C. aurantifolia peels using a stepwise in silico-based analysis. We first identified the unique proteins of P. falciparum that have no homolog in the human proteome, and then performed inverse docking, ΔGBinding calculation, and molecular dynamics simulation to predict the binding affinity and stability of the isolated compounds with these proteins. We found that limonin (2), luteolin (3), and myricetin (5) could interact with 20S a proteasome, choline kinase, and phosphocholine cytidylyltransferase, respectively, which are important enzymes for the survival and growth of the parasite. According to our findings, phytochemicals from C. aurantifolia peels can be considered as potential leads for the development of new safe and effective antiplasmodial agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota is involved in the pathogenesis of diabetic cardiomyopathy (DCM). Myricetin protects cardiac function in DCM. However, the low bioavailability of myricetin fails to explain its pharmacological mechanisms thoroughly. Research has shown that myricetin has a positive effect on the gut microbiota. We hypothesize that myricetin improves the development of DCM via regulating gut microbiota. Methods: DCM mice were induced with streptozotocin and fed a high-fat diet, and then treated with myricetin by gavage and high-fat diet for 16 weeks. Indexes related to gut microbiota composition, cardiac structure, cardiac function, intestinal barrier function, and inflammation were detected. Moreover, the gut contents were transplanted to DCM mice, and the effect of fecal microbiota transplantation (FMT) on DCM mice was assessed. Results: Myricetin could improve cardiac function in DCM mice by decreasing cardiomyocyte hypertrophy and interstitial fibrosis. The composition of gut microbiota, especially for short-chain fatty acid-producing bacteria involving Roseburia, Faecalibaculum, and Bifidobacterium, was more abundant by myricetin treatment in DCM mice. Myricetin increased occludin expression and the number of goblet cells in DCM mice. Compared with DCM mice unfed with gut content, the cardiac function, number of goblet cells, and expression of occludin in DCM mice fed by gut contents were elevated, while cardiomyocyte hypertrophy and TLR4/MyD88 pathway-related proteins were decreased. Conclusions: Myricetin can prevent DCM development by increasing the abundance of beneficial gut microbiota and restoring the gut barrier function. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

As the water molecules found at the interface of lipid bilayers exhibit distinct structural and reorientation dynamics compared to water molecules found in bulk, the fluctuations in their hydrogen bond (HB) network are expected to be different from those generated by the bulk water molecules. The research presented here aims to gain an insight into temperature-dependent fluctuations of a HB network of water molecules found in an interfacial layer of multilamellar liposomes (MLVs) composed of anionic 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) lipids. Besides suspending DMPS lipids in phosphate buffer saline (PBS) of different pH values (6.0, 7.4, and 8.0), the changes in HB network fluctuations were altered by the incorporation of a non-polar flavonoid molecule myricetin (MCE) within the hydrocarbon chain region. By performing a multivariate analysis on the water combination band observed in temperature-dependent FTIR spectra, the results of which were further mathematically analyzed, the temperature-dependent fluctuations of interfacial water molecules were captured; the latter were the greatest for DMPS in PBS with a pH value of 7.4 and in general were greater for DMPS multibilayers in the absence of MCE. The presence of MCE made DMPS lipids more separated, allowing deeper penetration of water molecules towards the non-polar region and their restricted motion that resulted in decreased fluctuations. The experimentally observed results were supported by MD simulations of DMPS (+MCE) lipid bilayers. [ABSTRACT FROM AUTHOR]

Background: Ajuga integrifolia (Armagusa) is used as a decoction to treat high blood pressure and diabetes, widely in Ethiopia. Specific compounds for anti-hypertension activity were not identified so far. This study aims to provide a scientific basis for the therapeutic use of A. integrifolia as an antihypertension agent. Methods: In silico studies were used to evaluate the antihypertensive components of A. integrifolia. Flavonoids identified using HPLC analysis and iridoid glycosides isolated from A. integrifolia in this study and those isolated from synonyms (A. remota and A. bractosa) were considered in the molecular docking study. Interactions were studied by using Autodock vina (1.2) on PyRx 0.8 and visualizing in 2D and 3D using ligPlot+ and Discovery studio software. Activities like vasoprotection and druglikeness properties were predicted using online servers. Results: Flavonoids such as quercetin, myricetin, and rutin were identified and quantified by HPLC analysis from different extracts of A. integrifolia. Reptoside and 8-O-acetylharpgide isolated from the aerial part of A. integrifolia. The binding energies of all 17 candidates considered in this study range from − 10.2 kcal/mol to − 7.5 kcal/mol and are lower than enalapril (reference drug: − 5.9 kcal/mol). The binding energies, in most case, constitute hydrogen bonding. Biological activity predicted using PASS test also showed that the flavonoids have more probability of activity than the iridoid glycosides. Druglikeness properties of the candidate molecules showed that most follow the Lipinski rule of five with few violations. Conclusion: Lower binding energies involving hydrogen bonding and predicted activities concerning hypertension confirm the traditional use of the aerial part of the medicinal plant concerned. Flavonoids: rutin, myricetin, quercetin, and kaempferol take the leading role in the antihypertensive activity of the aerial part of A. integrifolia. The iridoid glycosides studied are almost similar in their effect on their antihypertensive activity and still better than the reference drug. [ABSTRACT FROM AUTHOR]

In this study, the dnaK gene-deletion mutant strain of Escherichia coli BW25113 showed a higher susceptibility than the wild-type strain of E. coli BW25113 to phage S127BCL3. Flavonoids, myricetin and quercetin which had been reported to suppress the role of DnaK were tested to examine their effects on the phage susceptibility of E. coli BW25113. A 6-h pretreatment with 500 µmol/L myricetin or quercetin increased the phage susceptibility of E. coli BW25113. A similar result was observed in E. coli O157:H7. Real-time quantitative polymerase chain reaction (qPCR) was conducted to investigate the effects of flavonoids on the transcription of chaperone genes (dnaK, dnaJ, groEL, and grpE) in E. coli. Pretreatment of wild-type E. coli BW25113 with flavonoids decreased the transcription of chaperone genes. This is the first report demonstrating the enhancement of the phage susceptibility of both E. coli BW25113 and E. coli O157:H7 by flavonoids. The results of this study on the combined effects of flavonoids involved in foods and phages on E. coli provide scientific bases for development of a novel biocontrol method of foodborne bacteria. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN), a leading cause of end-stage renal disease, remains a formidable challenge in diabetes management due to the complex nature of its pathogenesis, particularly the epithelial-mesenchymal transition (EMT) process. Our innovative study leverages network pharmacology to explore the therapeutic potentials of Myricetin, a natural flavonoid, focusing on its effects against NOX4, a critical mediator in DN progression. This investigation marks a pioneering approach by integrating network pharmacology to predict and elucidate the inhibitory relationship between Myricetin and NOX4. Utilizing a high-fat diet/streptozotocin (HFD/STZ) induced DN mouse model, we delved into the effects of Myricetin on renal EMT processes. Through network pharmacology analyses coupled with molecular docking studies, we identified and confirmed Myricetin's binding efficacy to NOX4. Extensive in vitro and in vivo experiments further established Myricetin's significant impact on mitigating EMT by modulating the NOX4-NF-κB-Snail signaling pathway. Results from our research demonstrated notable improvements in renal function and reductions in tissue fibrosis among treated HFD/STZ mice. By curtailing NOX4 expression, Myricetin effectively reduced reactive oxygen species (ROS) production, thereby inhibiting NF-κB activation and subsequent Snail expression, crucial steps in the EMT pathway. Supported by both theoretical predictions and empirical validations, this study unveils the mechanism underlying Myricetin's modulation of EMT in DN through disrupting the NOX4-NF-κB-Snail axis. These findings not only contribute a new therapeutic avenue for DN treatment but also underscore the utility of network pharmacology in advancing drug discovery processes.

Background: Alzheimer's disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin. Methods: The effect of myricetin was assessed on Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3β (GSK3β) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress. Results: We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aβ42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3β and ERK 2 signalling pathways. Conclusions: This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer’s disease.

Abstract Reactive oxygen species (ROS)‐mediated oxidative stress and apoptosis contribute to the pathogenesis and pathological conditions of various diseases induced by food and environmental pollutants. Myricetin and dihydromyricetin, as natural flavonoids, can counteract oxidative damage, apoptosis, and associated diseases. Molecular docking analysis, ELISA, fluorescence spectroscopy, and Western blot techniques were applied to examine the potential of the two flavonoids as effective therapeutics for ROS‐mediated diseases and the mechanism(s) underlying their protective effects against ethanol/H2O2‐induced damage. In Kunming mice and HepG2 cells, myricetin and dihydromyricetin inhibited ethanol/H2O2‐induced liver damage, ROS accumulation, and oxidative stress and apoptosis. Molecular docking showed that myricetin and dihydromyricetin interacted with JNK1 via hydrophobic interactions and hydrogen bonds, thereby exerting their protective effects. The significant differences in their binding patterns to JNK1 resulted from the different bond types between C2 and C3 on their C ring. Myricetin and dihydromyricetin likely protected liver injury via counteracting ROS/JNK1‐mediated oxidative stress and apoptosis. The finding that the suppression of ROS‐mediated oxidative stress and apoptosis by flavonoids via interacting with functional proteins, such as kinase, may represent an alternative strategy for treating excessive ROS‐induced health problems.