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...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.Never-theless,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-1βinduced 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.展开更多
Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in mice.Methods:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an a...Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in mice.Methods:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an alternative day for 14 days,followed by administration of myricetin(50,100,and 200 mg/kg)till day 21.Nasal symptoms,biochemical parameters,protein expressions,and histopathology were observed.Results:OVA-induced increased nasal symptoms including rubbing,sneezing,and discharge were significantly reduced by myricetin(100and 200 mg/kg)(P<0.05).Myricetin also protected against histamine challenge and attenuated elevated serum immunoglobulin E(IgE;total and OVA-specific),total IgG1,andβ-hexosaminidase levels,as well as leukotriene C4 and interleukins levels in nasal lavage fluid(P<0.05).Western blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells,while downregulating the protein expression of GATA binding protein 3,NF-κB,and IκB-α(P<0.05).Additionally,OVA-induced histopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment(P<0.05).Conclusions:Myricetin exerts anti-allergic effects against OVAinduced allergic rhinitis via regulating Th1/Th2 balance.展开更多
Vine tea has been used as an herbal tea by several ethnic minorities for hundreds of years in China.Flavonoids,a kind of indispensable component in a variety of nutraceutical,pharmaceutical and cosmetic applications,a...Vine tea has been used as an herbal tea by several ethnic minorities for hundreds of years in China.Flavonoids,a kind of indispensable component in a variety of nutraceutical,pharmaceutical and cosmetic applications,are identified to be the major metabolites and bioactive ingredients in vine tea.Interestingly,vine tea exhibits a wide range of significant bioactivities including anti-oxidant,anti-inflammatory,anti-tumor,antidiabetic,neuroprotective and other activities,but no toxicity.These bioactivities,to some extent,enrich the understanding about the role of vine tea in disease prevention and therapy.The health benefits of vine tea,particularly dihydromyricetin and myricetin,are widely investigated.However,there is currently no comprehensive review available on vine tea.Therefore,this report summarizes the most recent studies investigating bioactive constituents,pharmacological effects and possible mechanisms of vine tea,which will provide a better understanding about the health benefits and preclinical assessment of novel application of vine tea.展开更多
Objective: To explore the therapeutic effect and mechanism of myricctin on disseminated intravascular coagulation(DIC). Methods: The DIC model was established by injection of60 mg/kg LPS in KM mice, and the treatment ...Objective: To explore the therapeutic effect and mechanism of myricctin on disseminated intravascular coagulation(DIC). Methods: The DIC model was established by injection of60 mg/kg LPS in KM mice, and the treatment groups were injected myricetin with different concentrations(25 or 50 mg/kg) 30 min before the model was established. Both coagulation indicators and organ function were tested, including PT, APTT, fibrinogen. AST, ALT. BUN and tissue section. In vitro, the inflammatory model of RAW 264.7 macrophage cells were established by 10 μg/mL LPS. The treatment group was treated with 50 μmol/mL myricetin for 30 min before LPS, and the expression of TNF-a and p-NF-KB was detected, further to explore the therapeutic mechanism. Results: LPS-induced DIC led to a reduction of fibrinogen and a rise of PT, APTT,AST, ALT, BUN levels, but the treatment of myricctin significantly inhibited these abnormalities. Histopathology analysis also revealed that myricetin remarkably protected the liver and renal damage. In vitro, the expression of TNF-α and p-NF-κB induced by LPS was repressed by myricetin. Conclusions: This study provides new insights into the protective effects of myricetin in LPS-induced DIC by anticoagulant and anti-inflammatory via suppressing the activation of p-NF-κB which decreased TNF-α level.展开更多
The aim of the present study was to compare the ability of the myricetin and quercetin to modulate the oxidative DNA damage induced by 2-amino-3, 8- dimethylimidazo [4,5-f] quinoxaline (8-MeIQx), 2-amino- 3, 4, 8- tri...The aim of the present study was to compare the ability of the myricetin and quercetin to modulate the oxidative DNA damage induced by 2-amino-3, 8- dimethylimidazo [4,5-f] quinoxaline (8-MeIQx), 2-amino- 3, 4, 8- trimethylimidazo [4, 5-f]-quinoxaline (4,8-diMeIQx) and 2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine (PhIP), in human hepatoma cells. DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or comet assay. None of the myricetin and quercetin concentrations tested protected against 8-MeIQx, 4, 8-diMeIQx and PhIP-induced DNA strand breaks. The oxidized pyrimidines induced by 4, 8-diMeIQx and PhIP were reduced by myricetin but not by quercetin. Quercetin reduced the oxidized purines induced by 8-MeIQx and PhIP, while myricetin also reduced the induced by 4, 8-diMeIQx. One feasible mechanism by which myricetin and quercetin exert their protective effect towards HCAs-induced oxidative DNA could be related in part to the reduction of human CYP1A1. Another mechanism claimed to be responsible for the protective effect of myricetin and quercetin is the induction of phase II metabolizing enzymes such as UDP-glucuronyltrasferase (UGT). The ethoxyresorufin O-deethylation (CYP1A1) activity was moderately inhibited by myricetin, while little effect was observed by quercetin. On the contrary, quercetin showed the greatest increase on UDP-glucuronyltransferase activity. However, these are not the only mechanisms by which myricetin and quercetin exert their protective effect, other mechanisms such as stimulation of the repair of carcinogen-induced DNA damage and or the free radical scavenging efficiency have been also implicated. In conclusion, our results clearly indicate that myricetin was more efficient than quercetin to prevent DNA damage (oxidized purines and pyrimidines) induced by the three HCAs evaluated. This protective effect depends on the chemical structure of flavonoid and the mutagen studied.展开更多
The simultaneous electrochemical determination of myricetin and rutin remains a challenge due to their indistinguishable potentials.To solve this problem,we constructed a ternary platinum nanoparticle,reduced graphene...The simultaneous electrochemical determination of myricetin and rutin remains a challenge due to their indistinguishable potentials.To solve this problem,we constructed a ternary platinum nanoparticle,reduced graphene oxide,multi-walled carbon nanotubes (Pt@r-GO@MWCNTs) nanocomposite via a facile one-pot synthetic method.Under the optimized conditions,the ternary Pt@r-GO@MWCNTs nanocomposite exhibited good electrocatalytic activity toward myricetin and rutin via solid phase extraction and excellent performance for the simultaneous determination of myricetin and rutin.The oxidation peak current of myricetin was proportional to its concentrations in the range of 0.05-50μM with a detection limit of 0.01μM (S/N=3).The linear range for rutin was 0.05-50μM with a detection limit of 0.005μM(S/N=3).The ternary nanocomposite sensor also exhibited good reproducibility and stability,and was successfully used for the simultaneous determination of myricetin and rutin in real orange juice samples with recoveries ranging between 100.57% and 108.46%.展开更多
Flavonoids have been reported to possess strong antioxidant activities that moderate endothelial dysfunction and demonstrate protective effects on cardiovascular disease. Our previous studies confirmed that flavonoids...Flavonoids have been reported to possess strong antioxidant activities that moderate endothelial dysfunction and demonstrate protective effects on cardiovascular disease. Our previous studies confirmed that flavonoids, including hesperidin, naringin and nobiletin, inhibited thrombogenesis and hypertension in stroke prone spontaneously hypertensive rats (SHRSP) by protecting the endothelium from the adverse effects of free radical formation. We have now further investigated the protective effects of myricetin and hesperidin on cerebral thrombosis and atherogenesis in apolipoprotein E (apoE) and lowdensity lipoprotein receptor (LDLR) deficient (Apoe-/- and Ldlr-/- double knockout) mice. Three groups of mice were fed high fat diet alone and high fat diet mixed with myricetin (100 mg/kg/day and 200 mg/kg/day) or glucosyl hesperidin (G-hesperidin;250 mg/kg/day and 500 mg/kg/day) for 8 weeks. There were no differences in body weight related to administration of the flavonoids. Thrombotic tendency was assessed using a He-Ne laser technique in the murine cerebral pial vessels. In addition, atherogenesis was quantified histologically after dissection of the aorta from each mouse and staining with Oil Red O solution. The percentages of stained area to whole area of dissected aorta were calculated as indices of anti-atherogenic activity. Both myricetin and G-hesperidin significantly inhibited thrombogenesis in vivo and significantly inhibited atherogenesis compared to control mice (p < 0.001). These findings demonstrated that daily intake of myricetin and hesperidin suppressed the development of atherogenesis and thrombogenesis, possibly associated with the potent antioxidant effects of the flavonoids.展开更多
OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be induced by interferon-γ(IFN-γ)in the tumor microenvironment,leading to immune escape of tumors.Myr...OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be induced by interferon-γ(IFN-γ)in the tumor microenvironment,leading to immune escape of tumors.Myricetin(MY)is a flavonoid distributed in many edible and medicinal plants.The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells.METHODS Expressions of PD-L1 and major histocompatibility complex-I(MHC-I)were evaluated by flow cytometry and Western blotting,and the expression of IDO1 was measured by Western blotting.qRT-PCR was used to detect their mRNA levels.The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1.Molecular docking analysis,Western blotting and immunofluorescence were used for mechanism study.RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells,while didn't show obvious effect on the expression of MHC-I.In addition,MY restored the survival,proliferation,CD69 expression and interleukin-2(IL-2)secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system.Mechanistically,IFN-γup-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis,which was targeted and inhibited by MY.CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression,supporting the potential of MY in anti-tumor immunotherapy.展开更多
Phosphoinositide-dependent protein kinase-1 (PDK1), the class of serine threonine kinase, is a master regulator of the AGC family of kinases. It is a main component of the PI3K pathway. As it is reported that this pat...Phosphoinositide-dependent protein kinase-1 (PDK1), the class of serine threonine kinase, is a master regulator of the AGC family of kinases. It is a main component of the PI3K pathway. As it is reported that this pathway is most commonly, and this pathway is the most commonly deregulated among many cancers. So designing a selective inhibitor of PDK1 may have the efficacy as an anticancer agent. Herein, we describe our work focused on the structure based on screening of 95% similar analogues of Myricetin deposited in PubChem database as earlier studies have been suggested that myricetin acts as an anti cancer agent. Further molecular docking as well as the in silico ADMET studies are incorporated on these compounds to evaluate the binding and pharmacokinetic properties of these compounds. Due to low oral bioavailability, clinical use of myricetin is limited. Therefore this study is an attempt towards screening of structurally similar better compounds as compare with myricetin which can act as better inhibitor against PDK-1.展开更多
There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The...There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventricular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer's disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 m L/kg saline. Behavioral test(the shuttle box test) was performed on day 22 to examine learning and memory in rats. Immediately after that, hematoxylin-eosin staining was performed to observe the morphological change in hippocampal CA3 pyramidal neurons. Myricetin greatly increased the number of hippocampal CA3 pyramidal neurons and improved learning and memory impairments in rats with Alzheimer's disease. These findings suggest that myricetin is beneficial for treatment of Alzheimer's disease.展开更多
The geometry of myricetin and dihydromyricetin was optimized by DMol3 program based on DFT. The optimized structures have been proved to be stable by real frequencies obtained.The parameters of geometry optimization,v...The geometry of myricetin and dihydromyricetin was optimized by DMol3 program based on DFT. The optimized structures have been proved to be stable by real frequencies obtained.The parameters of geometry optimization,vibration frequencies,atomic charges,thermodynamics,Fukui functions,and frontier molecular orbital had been obtained. The thermodynamic properties of 2 molecules were fitted and the relationship between the thermodynamic function and temperature was obtained. The correlation coefficient of the obtained equations is larger than 0.99,indicating that the function is approximately linear in the whole temperature range. The calculated results showed the O–H molecular structures were the main group affecting the antioxidant activity and the oxygen in the benzene ring is the electrophilic reaction site. Ortho-OH on the benzene formed intramolecular hydrogen bonds,which contributed to the stability of the benzene ring. It may be the active site for the occurrence of the reaction.展开更多
Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and ...Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial(antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.展开更多
Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin(MYR)...Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin(MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate(IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin–isonicotinamide(MYR–INM) and myricetin–caffeine(MYR–CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure.The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer(CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR–INM(1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.展开更多
Objective:Myricetin 3-O-galactoside is an active compound with pharmaceutical potential.The insufficient supply of this compound becomes a bottleneck in the druggability study of myricetin 3-Ogalactoside.Thus,it is ne...Objective:Myricetin 3-O-galactoside is an active compound with pharmaceutical potential.The insufficient supply of this compound becomes a bottleneck in the druggability study of myricetin 3-Ogalactoside.Thus,it is necessary to develop a biosynthetic process for myricetin 3-O-galactoside through metabolic engineering.Methods:Two genes OcSUS1 and OcUGE1 encoding sucrose synthase and UDP-glucose 4-epimerase were introduced into BL21(DE3)to reconstruct a UDP-D-galactose(UDP-Gal)biosynthetic pathway in Escherichia coli.The resultant chassis strain was able to produce UDP-Gal.Subsequently,a flavonol 3-O-galactosyltransferase DkFGT gene was transformed into the chassis strain producing UDP-Gal.An artificial pathway for myricetin 3-O-galactoside biosynthesis was thus constructed in E.coli.Results:The obtained engineered strain was demonstrated to be capable of producing myricetin 3-Ogalactoside,reaching 29.7 mg/L.Conclusion:Biosynthesis of myricetin 3-O-galactoside through engineered E.coli could be achieved.This result lays the foundation for the large-scale preparation of myricetin 3-O-galactoside.展开更多
基金Supported by National Natural Science Foundation of China,No.82205025,No.82374355 and No.82174293Subject of Jiangsu Province Hospital of Chinese Medicine,No.Y21023Forth Batch of Construction Program for Inheritance Office of Jiangsu Province Famous TCM Experts,No.[2021]7.
文摘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.Never-theless,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-1βinduced 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.
文摘Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in mice.Methods:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an alternative day for 14 days,followed by administration of myricetin(50,100,and 200 mg/kg)till day 21.Nasal symptoms,biochemical parameters,protein expressions,and histopathology were observed.Results:OVA-induced increased nasal symptoms including rubbing,sneezing,and discharge were significantly reduced by myricetin(100and 200 mg/kg)(P<0.05).Myricetin also protected against histamine challenge and attenuated elevated serum immunoglobulin E(IgE;total and OVA-specific),total IgG1,andβ-hexosaminidase levels,as well as leukotriene C4 and interleukins levels in nasal lavage fluid(P<0.05).Western blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells,while downregulating the protein expression of GATA binding protein 3,NF-κB,and IκB-α(P<0.05).Additionally,OVA-induced histopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment(P<0.05).Conclusions:Myricetin exerts anti-allergic effects against OVAinduced allergic rhinitis via regulating Th1/Th2 balance.
文摘Vine tea has been used as an herbal tea by several ethnic minorities for hundreds of years in China.Flavonoids,a kind of indispensable component in a variety of nutraceutical,pharmaceutical and cosmetic applications,are identified to be the major metabolites and bioactive ingredients in vine tea.Interestingly,vine tea exhibits a wide range of significant bioactivities including anti-oxidant,anti-inflammatory,anti-tumor,antidiabetic,neuroprotective and other activities,but no toxicity.These bioactivities,to some extent,enrich the understanding about the role of vine tea in disease prevention and therapy.The health benefits of vine tea,particularly dihydromyricetin and myricetin,are widely investigated.However,there is currently no comprehensive review available on vine tea.Therefore,this report summarizes the most recent studies investigating bioactive constituents,pharmacological effects and possible mechanisms of vine tea,which will provide a better understanding about the health benefits and preclinical assessment of novel application of vine tea.
基金supported by Hainan Provincial Natural Seience Foundation of China(818MS140)
文摘Objective: To explore the therapeutic effect and mechanism of myricctin on disseminated intravascular coagulation(DIC). Methods: The DIC model was established by injection of60 mg/kg LPS in KM mice, and the treatment groups were injected myricetin with different concentrations(25 or 50 mg/kg) 30 min before the model was established. Both coagulation indicators and organ function were tested, including PT, APTT, fibrinogen. AST, ALT. BUN and tissue section. In vitro, the inflammatory model of RAW 264.7 macrophage cells were established by 10 μg/mL LPS. The treatment group was treated with 50 μmol/mL myricetin for 30 min before LPS, and the expression of TNF-a and p-NF-KB was detected, further to explore the therapeutic mechanism. Results: LPS-induced DIC led to a reduction of fibrinogen and a rise of PT, APTT,AST, ALT, BUN levels, but the treatment of myricctin significantly inhibited these abnormalities. Histopathology analysis also revealed that myricetin remarkably protected the liver and renal damage. In vitro, the expression of TNF-α and p-NF-κB induced by LPS was repressed by myricetin. Conclusions: This study provides new insights into the protective effects of myricetin in LPS-induced DIC by anticoagulant and anti-inflammatory via suppressing the activation of p-NF-κB which decreased TNF-α level.
文摘The aim of the present study was to compare the ability of the myricetin and quercetin to modulate the oxidative DNA damage induced by 2-amino-3, 8- dimethylimidazo [4,5-f] quinoxaline (8-MeIQx), 2-amino- 3, 4, 8- trimethylimidazo [4, 5-f]-quinoxaline (4,8-diMeIQx) and 2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine (PhIP), in human hepatoma cells. DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or comet assay. None of the myricetin and quercetin concentrations tested protected against 8-MeIQx, 4, 8-diMeIQx and PhIP-induced DNA strand breaks. The oxidized pyrimidines induced by 4, 8-diMeIQx and PhIP were reduced by myricetin but not by quercetin. Quercetin reduced the oxidized purines induced by 8-MeIQx and PhIP, while myricetin also reduced the induced by 4, 8-diMeIQx. One feasible mechanism by which myricetin and quercetin exert their protective effect towards HCAs-induced oxidative DNA could be related in part to the reduction of human CYP1A1. Another mechanism claimed to be responsible for the protective effect of myricetin and quercetin is the induction of phase II metabolizing enzymes such as UDP-glucuronyltrasferase (UGT). The ethoxyresorufin O-deethylation (CYP1A1) activity was moderately inhibited by myricetin, while little effect was observed by quercetin. On the contrary, quercetin showed the greatest increase on UDP-glucuronyltransferase activity. However, these are not the only mechanisms by which myricetin and quercetin exert their protective effect, other mechanisms such as stimulation of the repair of carcinogen-induced DNA damage and or the free radical scavenging efficiency have been also implicated. In conclusion, our results clearly indicate that myricetin was more efficient than quercetin to prevent DNA damage (oxidized purines and pyrimidines) induced by the three HCAs evaluated. This protective effect depends on the chemical structure of flavonoid and the mutagen studied.
基金financially supported by the National Natural Science Foundation of China (Grant No.21874047,21475046, 21427809)
文摘The simultaneous electrochemical determination of myricetin and rutin remains a challenge due to their indistinguishable potentials.To solve this problem,we constructed a ternary platinum nanoparticle,reduced graphene oxide,multi-walled carbon nanotubes (Pt@r-GO@MWCNTs) nanocomposite via a facile one-pot synthetic method.Under the optimized conditions,the ternary Pt@r-GO@MWCNTs nanocomposite exhibited good electrocatalytic activity toward myricetin and rutin via solid phase extraction and excellent performance for the simultaneous determination of myricetin and rutin.The oxidation peak current of myricetin was proportional to its concentrations in the range of 0.05-50μM with a detection limit of 0.01μM (S/N=3).The linear range for rutin was 0.05-50μM with a detection limit of 0.005μM(S/N=3).The ternary nanocomposite sensor also exhibited good reproducibility and stability,and was successfully used for the simultaneous determination of myricetin and rutin in real orange juice samples with recoveries ranging between 100.57% and 108.46%.
文摘Flavonoids have been reported to possess strong antioxidant activities that moderate endothelial dysfunction and demonstrate protective effects on cardiovascular disease. Our previous studies confirmed that flavonoids, including hesperidin, naringin and nobiletin, inhibited thrombogenesis and hypertension in stroke prone spontaneously hypertensive rats (SHRSP) by protecting the endothelium from the adverse effects of free radical formation. We have now further investigated the protective effects of myricetin and hesperidin on cerebral thrombosis and atherogenesis in apolipoprotein E (apoE) and lowdensity lipoprotein receptor (LDLR) deficient (Apoe-/- and Ldlr-/- double knockout) mice. Three groups of mice were fed high fat diet alone and high fat diet mixed with myricetin (100 mg/kg/day and 200 mg/kg/day) or glucosyl hesperidin (G-hesperidin;250 mg/kg/day and 500 mg/kg/day) for 8 weeks. There were no differences in body weight related to administration of the flavonoids. Thrombotic tendency was assessed using a He-Ne laser technique in the murine cerebral pial vessels. In addition, atherogenesis was quantified histologically after dissection of the aorta from each mouse and staining with Oil Red O solution. The percentages of stained area to whole area of dissected aorta were calculated as indices of anti-atherogenic activity. Both myricetin and G-hesperidin significantly inhibited thrombogenesis in vivo and significantly inhibited atherogenesis compared to control mice (p < 0.001). These findings demonstrated that daily intake of myricetin and hesperidin suppressed the development of atherogenesis and thrombogenesis, possibly associated with the potent antioxidant effects of the flavonoids.
基金Science and Technology Development Fund,Macao SAR(0129/2019/A3176/2017/A3)and University of Macao(MYRG2018-00165-ICMS)。
文摘OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be induced by interferon-γ(IFN-γ)in the tumor microenvironment,leading to immune escape of tumors.Myricetin(MY)is a flavonoid distributed in many edible and medicinal plants.The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells.METHODS Expressions of PD-L1 and major histocompatibility complex-I(MHC-I)were evaluated by flow cytometry and Western blotting,and the expression of IDO1 was measured by Western blotting.qRT-PCR was used to detect their mRNA levels.The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1.Molecular docking analysis,Western blotting and immunofluorescence were used for mechanism study.RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells,while didn't show obvious effect on the expression of MHC-I.In addition,MY restored the survival,proliferation,CD69 expression and interleukin-2(IL-2)secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system.Mechanistically,IFN-γup-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis,which was targeted and inhibited by MY.CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression,supporting the potential of MY in anti-tumor immunotherapy.
文摘Phosphoinositide-dependent protein kinase-1 (PDK1), the class of serine threonine kinase, is a master regulator of the AGC family of kinases. It is a main component of the PI3K pathway. As it is reported that this pathway is most commonly, and this pathway is the most commonly deregulated among many cancers. So designing a selective inhibitor of PDK1 may have the efficacy as an anticancer agent. Herein, we describe our work focused on the structure based on screening of 95% similar analogues of Myricetin deposited in PubChem database as earlier studies have been suggested that myricetin acts as an anti cancer agent. Further molecular docking as well as the in silico ADMET studies are incorporated on these compounds to evaluate the binding and pharmacokinetic properties of these compounds. Due to low oral bioavailability, clinical use of myricetin is limited. Therefore this study is an attempt towards screening of structurally similar better compounds as compare with myricetin which can act as better inhibitor against PDK-1.
基金funded by the Department of Biology,Faculty of Science,Arak University,Iran,No.38156-8-8349
文摘There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventricular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer's disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 m L/kg saline. Behavioral test(the shuttle box test) was performed on day 22 to examine learning and memory in rats. Immediately after that, hematoxylin-eosin staining was performed to observe the morphological change in hippocampal CA3 pyramidal neurons. Myricetin greatly increased the number of hippocampal CA3 pyramidal neurons and improved learning and memory impairments in rats with Alzheimer's disease. These findings suggest that myricetin is beneficial for treatment of Alzheimer's disease.
基金supported by the Science and Technology Project of Guangdong Province(2016B010122032)Natural Science Foundation of Guangdong Province(05300953)
文摘The geometry of myricetin and dihydromyricetin was optimized by DMol3 program based on DFT. The optimized structures have been proved to be stable by real frequencies obtained.The parameters of geometry optimization,vibration frequencies,atomic charges,thermodynamics,Fukui functions,and frontier molecular orbital had been obtained. The thermodynamic properties of 2 molecules were fitted and the relationship between the thermodynamic function and temperature was obtained. The correlation coefficient of the obtained equations is larger than 0.99,indicating that the function is approximately linear in the whole temperature range. The calculated results showed the O–H molecular structures were the main group affecting the antioxidant activity and the oxygen in the benzene ring is the electrophilic reaction site. Ortho-OH on the benzene formed intramolecular hydrogen bonds,which contributed to the stability of the benzene ring. It may be the active site for the occurrence of the reaction.
文摘Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial(antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.
基金sponsored by the "Shu Guang" project supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (15SG39, China)the Shanghai Pujiang Program (16PJD044, China)+1 种基金National Natural Science Foundation of China (81573814)the science and technology project supported by the Science and Technology Commission of Huangpu District (ZYKC201603008, China)
文摘Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin(MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate(IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin–isonicotinamide(MYR–INM) and myricetin–caffeine(MYR–CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure.The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer(CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR–INM(1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.
基金supported by National Mega-project for Innovative Drugs(2018ZX09711001-006)CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-3-012 and 2019-I2M-1005)+1 种基金Disciplines Construction Project(201920100801)Beijing Natural Science Foundation(7172143)。
文摘Objective:Myricetin 3-O-galactoside is an active compound with pharmaceutical potential.The insufficient supply of this compound becomes a bottleneck in the druggability study of myricetin 3-Ogalactoside.Thus,it is necessary to develop a biosynthetic process for myricetin 3-O-galactoside through metabolic engineering.Methods:Two genes OcSUS1 and OcUGE1 encoding sucrose synthase and UDP-glucose 4-epimerase were introduced into BL21(DE3)to reconstruct a UDP-D-galactose(UDP-Gal)biosynthetic pathway in Escherichia coli.The resultant chassis strain was able to produce UDP-Gal.Subsequently,a flavonol 3-O-galactosyltransferase DkFGT gene was transformed into the chassis strain producing UDP-Gal.An artificial pathway for myricetin 3-O-galactoside biosynthesis was thus constructed in E.coli.Results:The obtained engineered strain was demonstrated to be capable of producing myricetin 3-Ogalactoside,reaching 29.7 mg/L.Conclusion:Biosynthesis of myricetin 3-O-galactoside through engineered E.coli could be achieved.This result lays the foundation for the large-scale preparation of myricetin 3-O-galactoside.
