A series of 4-thioflavonols compounds were synthesized by treating flavonols with lawsons reagent with variable substituent groups at A, B, and AB rings. All the synthesized compounds were checked for antibacterial an...A series of 4-thioflavonols compounds were synthesized by treating flavonols with lawsons reagent with variable substituent groups at A, B, and AB rings. All the synthesized compounds were checked for antibacterial and antifungal activity. We report that many compounds were found active against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, bacterial strains and, C. albicans, C. parapsilosisstrains and C. krusei fungal strains. Most of the synthesized 4-thioflavonols compounds were found to show enhanced antimicrobial activity than respective flavonol compounds.展开更多
The cell cycle checkpoint system play a pivotal role in the cellular DNA damage response, and the discovery of checkpoint inhibitors is expected to sensitize current cancer therapies. Checkpoint signaling cascades are...The cell cycle checkpoint system play a pivotal role in the cellular DNA damage response, and the discovery of checkpoint inhibitors is expected to sensitize current cancer therapies. Checkpoint signaling cascades are critically modulated by ATM (ataxia telangiectasia-mutated) and its related molecules. Generally, ATM primarily responds to ionizing irradiation-induced DNA double-strand breaks. Heavy ions from an accelerated carbon ion beam have been used to cure cancer because they are more effective than ionizing irradiation such as X-ray and γ-radiation in terms of biological damage. In a previous study, we demonstrated that a persimmon leaf flavonol (PLF) promoted the cytotoxic effect of chemotherapeutic agents on cancer cells through inhibition of checkpoint activities, especially in the ATM dependent pathway. The present study investigated whether PLF inhibits checkpoint activity during the DNA damage response induced by heavy ion irradiation. Treatment with PLF significantly increased the cytotoxicity of heavy ion irradiation in A549 adenocarcinoma cells. The phosphorylation of checkpoint proteins such as p53, SMC1, and Chk1 was increased by heavy ions. PLF reduced the phosphorylation of checkpoint proteins. Pre-treatment with PLF significantly prevented the decrease of mitotic cells in heavy ion-exposed cells. We further evaluated tumor volume in SCID mice inoculated with human lung adenocarcinoma A549 cells. The combination treatment of PLF and heavy ion resulted in a decrease of tumor volume compared with controls, although PLF itself did not exhibit any effect. These results indicate that PLF inhibits tumor growth through modulation of the DNA damage response. PLF may be useful for clinical application in combination with heavy ion radiotherapy.展开更多
Flavonols were extracted from Acanthopanax Senticosus Harms by Soxhlet extraction（SE）,atmospheric pressure microwave-assisted extraction（AMAE） and pressurized microwave-assisted extraction（PMAE）.The influences o...Flavonols were extracted from Acanthopanax Senticosus Harms by Soxhlet extraction（SE）,atmospheric pressure microwave-assisted extraction（AMAE） and pressurized microwave-assisted extraction（PMAE）.The influences of experimental conditions,such as concentration of ethanol in the eluent,microwave irradiation time,etc.on the extraction yield were studied.Four flavonols（hyperin,rutin,quercitrin and quercetin） in the extracts were determined quantitatively by HPLC method.The experimental results demonstrate the advantages of PMAE and AMAE over those of conventional SE,that is the extraction time is dramatically reduced,and the yields of flavonols are effective improved.Although the yield of flavonols is higher and the extraction time is shorter by PMAE than those of AMAE,flavonols are easy to be decomposed over a certain time.展开更多
The enthalpies of bond dissociations of the hydroxyl groups, the energy of the highest occupied molecular orbitals and the corresponding radicals spin densities of all possible ten isomeric mono-hydroxyl flavones are ...The enthalpies of bond dissociations of the hydroxyl groups, the energy of the highest occupied molecular orbitals and the corresponding radicals spin densities of all possible ten isomeric mono-hydroxyl flavones are calculated by means of 3-parameter Becke, Lee, Yang and Parr functional. The structural factors affecting these descriptors of radical-scavenging activity are outlined. The results obtained show that the hydroxyl groups in ring A and C are more involved in the process of a radical-capturing than recently believed.展开更多
Hsp90 is a major protein involved in the stabilization of various proteins in cancer cells.The present investigation focused on the molecular docking simulation studies of flavanols as inhibitors of Hsp90 at the high ...Hsp90 is a major protein involved in the stabilization of various proteins in cancer cells.The present investigation focused on the molecular docking simulation studies of flavanols as inhibitors of Hsp90 at the high affinity adenosine triphosphate（ATP）binding site and analyzed absorption,distribution,metabolism,excretion and toxicity（ADME-toxicity）.The molecular docking analysis revealed that the flavanols showed competitive inhibition with ATP molecule at the active site and enhanced pharmacological parameters.展开更多
In this study,we designed a convenient method,to total synthesis of fl avonols especially for C-5 substituted ones and derivatives on a large scale.Beginning from the inexpensively available 2,4,6-trihydroxyacetopheno...In this study,we designed a convenient method,to total synthesis of fl avonols especially for C-5 substituted ones and derivatives on a large scale.Beginning from the inexpensively available 2,4,6-trihydroxyacetophenone through Aldol condensation reaction,I2/DMSO cyclization reaction,Oxone“one pot”oxidation,kaempferol(1)and derivative(2)was obtained in an overall yield of 35%.The structures of the target compound and key intermediates were verifi ed by MS,IR,1H-NMR and 13C-NMR techniques,and the structure of 5a was further confi rmed by X-ray diff raction analysis.展开更多
Flavonols and phenolic acids are key determinants of loquat nutritional quality,yet their inheritance remains unclear.In this study,high-performance liquid chromatography-photodiode array detector(HPLC-PDA)profiling o...Flavonols and phenolic acids are key determinants of loquat nutritional quality,yet their inheritance remains unclear.In this study,high-performance liquid chromatography-photodiode array detector(HPLC-PDA)profiling of mature fruits from 95 F_(1)individuals derived from Tangkebaisha'×'Algerie'identified seven flavonol glycosides and two phenolic acids.Among these,quercetin 3-Ogalactoside(Q3Gal)and kaempferol 3-O-rhamnoside(K3Rha)were the most abundant flavonols,whereas neochlorogenic acid(5-CQA)dominated the phenolic acid fraction in both peel and flesh.All the traits exhibited wide transgressive segregation(coefficient of variation(CV),39.86%-81.48%).Notably,K3Rha,kaempferol 3-O-glucoside(K3Glc),quercetin 3-O-rutinoside,and chlorogenic acid in fruit pulp showed high transmission ability(>110%)and significantly better-parent heterosis(8.86%-88.56%),indicating strong potential for phenolic enrichment.Within the F_(1)population,line J-TAL-029 accumulated746.79μg/g fresh weight(FW)of total flavonols,and J-TAL-087 reached 3100.76μg/g FW of total phenolic acids,both substantially exceeding parental levels.Significant positive correlations were observed among flavonol glycosides sharing the same aglycone(e.g.K3Rha vs.K3Glc),indicating the feasibility of indirect selection for superior individuals.These findings elucidate the genetic basis of key phenolic compounds in loquat and provide a foundation for biofortification through breeding.展开更多
Flavonols and flavanones are important bioactive compounds with multiple pharmacological activities and health benefits.Transcriptional activation of flavonol and flavanone biosynthesis has been studied extensively,wh...Flavonols and flavanones are important bioactive compounds with multiple pharmacological activities and health benefits.Transcriptional activation of flavonol and flavanone biosynthesis has been studied extensively,while little is known about the negative regulators.CRISPR/Cas9 gene-editing technology,with the advantage of precise genetic modification,is a desirable tool for breeding biofortified materials and exploring potential molecular mechanisms.In this study,a transcriptional repressor,Sl MYB32,was characterized in tomato fruit.Phenotype and metabolomic analyses confirmed that knockout of Sl MYB32 resulted in increased accumulation of flavonols and flavanones,especially about 1 mg g^(-1)FW of quercetin 3-O-rutinoside(rutin).Transcriptome analysis indicated that expression of key genes Sl PAL6,Sl4CL3 and Sl4CL4 as well as five candidate Sl UGTs were significantly up-regulated in slmyb32 mutants.Dual-luciferase and EMSA assays indicated Sl MYB32 could bind to and repress promoter activities of Sl PAL6 and Sl4CL3.Expression of 27 transcription factors belonging to 12 families was significantly changed in slmyb32 mutants,among which two Sl MYBs,two Sl NACs,two Sl AP2s and one Sl WRKY were clustered with known flavonoid regulators.Our results provide new insights into improving bioactive compounds in fruit and understanding negative regulatory mechanisms in flavonol and flavanone biosynthesis.展开更多
In this study,we aimed to elucidate the mechanism of flavonol-Cu(Ⅱ)coordination binding to human serum albumin(HSA)and its effect on cellular activity,focusing on the regulation by the number of B-ring hydroxyl group...In this study,we aimed to elucidate the mechanism of flavonol-Cu(Ⅱ)coordination binding to human serum albumin(HSA)and its effect on cellular activity,focusing on the regulation by the number of B-ring hydroxyl groups and Cu(Ⅱ)coordination.The number of B-ring hydroxyl groups was positively associated with fluorescence quenching ability,secondary structure modification,and protein affinity.The coordination of Cu(Ⅱ)altered the binding capacity,interaction,binding site,and binding kinetics between flavonols and proteins,as well as the secondary structure,fluorescence lifetime,and microscopic state of proteins.The number of B-ring hydroxyl groups was positively correlated with the ability of flavonols to inhibit HepG2 cell activity,and this correlation was not affected by Cu(Ⅱ)coordination.However,Cu(Ⅱ)binding weakened the ability of flavonols to inhibit HepG2 cell activity.This study contributes to a comprehensive understanding of how the number of hydroxyl groups in the B-ring of flavonols and the presence of copper ions affect their transport in the blood,providing new insights into the bioavailability of flavonols.展开更多
Flavonols possess significant medical value and are essential for plant stress resistance.These compounds constitute primary components of the nutritional value in onions,particularly in edible portions.While the flav...Flavonols possess significant medical value and are essential for plant stress resistance.These compounds constitute primary components of the nutritional value in onions,particularly in edible portions.While the flavonol biosynthetic pathway has been extensively studied,its regulatory mechanisms in onions remain incompletely understood.This investigation identified flavonol biosynthesis and regulatory genes through analysis of transcriptome and metabolomics data from different developmental stages of'SA1’.Two R2R3-MYB transcription factors,AcMYB12 and AcMYB29,were identified as positive regulators of onion flavonol biosynthesis.Transcriptional activation assays demonstrated that both could activate AcCHS,AcF3´H,and AcFLS.Yeast one-hybrid assays confirmed their direct binding to these gene promoters.The expression levels of flavonol pathway genes and flavonol contents in AcMYB12/AcMYB29-overexpressing onion calli and Arabidopsis plants were significantly higher than those in the control group.Transient silencing assays revealed partial functional redundancy between these two transcription factors.Notably,their regulatory capabilities exhibited significant differences.AcMYB12 predominantly regulates flavonol accumulation,while AcMYB29 specifically influences quercetin.Further investigation of the molecular mechanisms underlying differential regulation indicated variations in cis-elements within flavonol pathway gene promoters and differences in binding activity between transcription factors and cis-elements.展开更多
Flavonols, the main flavonoids in plant leaves, have newly been proposed as a H2O2 scavenger in guard cells. However, whether 5-aminolevulinic acid(5-ALA) is involved in regulating stomatal movement of apple(Malus ...Flavonols, the main flavonoids in plant leaves, have newly been proposed as a H2O2 scavenger in guard cells. However, whether 5-aminolevulinic acid(5-ALA) is involved in regulating stomatal movement of apple(Malus × domestica Borkh. ‘Fuji') leaves through flavonol accumulation remains unclear. In this study, using diphenylboric acid 2-amino ethyl ester(DPBA, a flavonol fluorescent dye) and a laser scanning confocal microscope,we observed that 5-ALA pretreatment significantly improved flavonol accumulation in guard cells of apple leaves, especially around the nucleus.Then we demonstrated that 5-ALA pretreatment inhibited ABA-induced stomatal closure via decreasing reaction oxygen species(ROS) accumulation in guard cells. Pretreatment with quercetin or kaempferol, two main kinds of flavonols in plants, also inhibited ABA-induced stomatal closure by decreasing ROS content in the guard cells. Furthermore, exogenous flavonols could suppress H2O2-induced stomatal closure in apple leaves.Taken together, we conclude that ALA-induced flavonol accumulation in guard cells is involved in the inhibitory effect of ALA on ABA-induced ROS accumulation and stomatal closure in apple leaves.展开更多
In this research, supercritical carbon dioxide extraction （SFE） showed better extraction etlect when compared with Solid- liquid extraction （SLE）, Soxhlet extraction （SEt and Ultrasonic extraction （UE）, not onl...In this research, supercritical carbon dioxide extraction （SFE） showed better extraction etlect when compared with Solid- liquid extraction （SLE）, Soxhlet extraction （SEt and Ultrasonic extraction （UE）, not only in the rate but also the time. The comparison among these three extraction modifiers, including acetone, ethanol and methanol demonstrated that ethanol was preferred to SFE due to its high extraction effect and low toxicology. In addition, parameter of SFE, influence of temperature and pressure were investigated, and the best extraction effect was achieved at the optima conditions, temperature of 40℃ and the pressure of 35 MPa. Thus, SFE is a highly effective method for flavonols extraction, requiring minimum energy and producing non-toxic byproduct. SFE-GC system is applied for the evaluation on flavonols that plays a key role in plant resistance to heavy metal, with its content and synthetase gene expression significantly increasing in plant when threatened by heavy metal. Besides, results indicated that flavonols can improve plant resistance to oxidative stress by quenching the redundant ROS in matrix.展开更多
[Objective]The aim was to identify the composition of pigments from Jujube fruit skin.[Method]Pigments were extracted from＇Lubei Dongzao＇,＇Lajiao Zao＇,＇Chengwu Dongzao＇,＇Dabailing＇and identificated by using hi...[Objective]The aim was to identify the composition of pigments from Jujube fruit skin.[Method]Pigments were extracted from＇Lubei Dongzao＇,＇Lajiao Zao＇,＇Chengwu Dongzao＇,＇Dabailing＇and identificated by using high performance liquid chromatography-mass spectrometry（HPLC-MS）.[Result]The results showed that eight flavanols and four to five flavonols were detected,no anthocyanins was detected.The contents of flavonoids were differnt in four varieties.The contents of flavanols（11 mg/g） and flavonols（1.78 mg/g） in＇Dabailing＇ were one-time higher than other varieties.Quercetin 3 rutinoside was the major flavonol.[Conclusion]The research provided theoretical basis for further study on mechanism of Jujube pigment turnning into the red.展开更多
Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this...Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.展开更多
Abstract： In the present study, we established an ultra performance liquid chromatography coupled with time-of-flight mass spectrometry （UPLC-QTOF-MSE） method to simultaneously quantify 33 components in Ginkgo bilo...Abstract： In the present study, we established an ultra performance liquid chromatography coupled with time-of-flight mass spectrometry （UPLC-QTOF-MSE） method to simultaneously quantify 33 components in Ginkgo biloba leaf extracts （GBEs）, including 17 flavonol glycosides, five terpene trilactones （TTLs）, four polyphenols and seven carboxylic acids. This optimized method was successfully applied to analyze the explicit compositions of GBE samples collected from different places. Furthermore, the data were processed through unsupervised principal component analysis （PCA） and supervised orthogonal partial least squared discrimination analysis （OPLS-DA） to evaluate the quality and compare the differences between the samples according to the contents of the 33 chemical constituents. Bilobalide, protocatechuic acid, shikimic acid, quinic acid, ginkgolide B, ginkgolide J, kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, quercetin-3-O-ct-L-rhamnopyranocyl-2＂-（6＇＂-p-coumaroyl）-β-D-glucoside and rutin were recognized as characteristic chemical markers that contributed most to control the quality of GBEs. Based on the fact that GBEs should be standardized with the characteristic components as quality control chemical markers, it is most important to maintain the quality of GBEs stable and reliable, and this method also provided a good strategy to further rectify and standardize the GBEs market.展开更多
A phytochemical investigation on the leaves of Cistus parviflorus led to the isolation of 18 compounds.The structures of the isolated compounds were elucidated as kaempferol 3-O-（3′′,6′′-di-O-E-p-coumaroyl）-β-D...A phytochemical investigation on the leaves of Cistus parviflorus led to the isolation of 18 compounds.The structures of the isolated compounds were elucidated as kaempferol 3-O-（3′′,6′′-di-O-E-p-coumaroyl）-β-D-glucopyranoside（1）,scopoletin（2）,kaempferol 3-O-（3′′-O-E-p-coumaroyl）-β-D-glucopyranoside（3）,kaempferol 3-O-（6′′-O-E-p-coumaroyl）-β-D-glucopyranoside（4）,kaempferol 3-O-β-D-glucopyranoside（5）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-（6′-O-E-p-coumaroyl）-β-D-glucopyranoside（6）,methyl flavogallonate（7）,quercetin 3-O-β-D-glucopyranoside（8）,quercetin 3-O-β-D-galactopyranoside（9）,hydroquinone（10）,arbutin（11）,methyl β-glucopyranoside（12）,shikimic acid（13）,（S）-1,2-propandiol-1-O-β-D-glucopyranoside（14）,benzyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（15）,2-phenethyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（16）,corchoionoside C（17）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-β-D-glucopyranoside（18） by the analysis of the MS and NMR spectroscopic data and comparison with the literature.Compounds 1–2,6–7,10–12,and 14–16 were isolated from Cistus genus for the first time.展开更多
This review was based on a literature search of PubM ed and Scielo databases using the keywords "quercetin,rutin,isoquercitrin,isoquercitin(IQ),quercetin-3-glucoside,bioavailability,flavonols and favonoids,and ca...This review was based on a literature search of PubM ed and Scielo databases using the keywords "quercetin,rutin,isoquercitrin,isoquercitin(IQ),quercetin-3-glucoside,bioavailability,flavonols and favonoids,and cancer" and combinations of all the words.We collected relevant scientific publications from 1990 to 2015 about the absorption,bioavailability,chemoprevention activity,and treatment effects as well as the underlying anticancer mechanisms of isoquercitin.Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom.The subclass of flavonols receives special attention owing to their health benefits.The main components of this class are quercetin,rutin,and IQ,which is a flavonoid and although mostly found as a glycoside,is an aglycone(lacks a glycoside side chain).This compound presents similar therapeutic profiles to quercetin but with superior bioavailability,resulting in increased efficacy compared to the aglycone form.IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant,antiproliferative,anti-inflammatory,anti-hypertensive,and anti-diabetic.The protective effects of IQ in cancer may be due to actions on lipid peroxidation.In addition,the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway,mixed-lineage protein kinase 3,mitogen-activated protein kinase,apoptotic pathways,as well proinflammatory protein signaling.This review contributed to clarifying the mechanisms of absorption,metabolism,and actions of IQ and isoquercitrin in cancer.展开更多
The fruits of the Sea buckthorn(Hippophae rhamnoides L.)are a popular plant food and a valuable health product.Cultivating plants produces a lot of leaves with fine branches as an unnecessary residue,which needs valor...The fruits of the Sea buckthorn(Hippophae rhamnoides L.)are a popular plant food and a valuable health product.Cultivating plants produces a lot of leaves with fine branches as an unnecessary residue,which needs valorization.The aim of the study was to estimate(by HPLC-MS/MS)the qualitative and quantitative content of polyphenolic compounds in different parts of H.rhamnoides(HR),and to determine the level of antioxidant activity of leaves and fruits(by DPPH,ABTS methods and ferrozine test).Up to 19 compounds were identified in different parts of HR.The fruits are rich in flavonoids,including various glycosides of flavonols isorhamnetin,quercetin,and kaempferol.Two isorhamnetin glycosides were not identified in the leaves,while isorhamnetin-3-rhamnosylglactosides and the ellagitannins hippophaenin B,stachyurin and casuarinin were present only in the leaves of the plant.The bark and roots contained considerably more catechins,but minimal flavonols than the fruits and leaves of HR.The total phenolics and flavonols were most abundant in water infusions from leaves of HR(especially quercetin-3-O-glucoside-7-O-rhamnoside),compared to methanolic extracts.No significant differences in the quantitative and qualitative content of the fresh and dried leaves were detected.The highest antioxidant activity by all three methods was detected in the leaves of HR.In addition to the fruits,the leaves may have a perspective as a source of biologically active substances of HR.展开更多
Flavonoids are widely used in industry for the prevention of various diseases. In daily life we are directly in touch with flavonoids due to their presence in different beverages, fruits and vegetables. Flavonoids are...Flavonoids are widely used in industry for the prevention of various diseases. In daily life we are directly in touch with flavonoids due to their presence in different beverages, fruits and vegetables. Flavonoids are mainly used as a coloring agent in plants, antioxidant and nutritional food for human. Flavonoids have explicit role in UV filtration, symbiotic nitrogen fixation and floral pigmentation. Flavonoids have potential for different biological activities like chelation of metals, decreasing platelets aggregation and cell signaling etc.展开更多
Stomach and colorectal cancers are common cancers and leading causes of cancer deaths.Because the alimentary tract can interact directly with dietary components,stomach and colorectal cancer may be closely related to ...Stomach and colorectal cancers are common cancers and leading causes of cancer deaths.Because the alimentary tract can interact directly with dietary components,stomach and colorectal cancer may be closely related to dietary intake.We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30,2012.Twenty-three studies out of 209 identified articles were finally selected for the analysis.Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies.Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio(OR)(95%CI) = 1.00(0.90-1.11) and 1.07(0.70-1.61),respectively].Among flavonoid subclasses,the intake of flavonols,flavan-3-ols,anthocyanidins,and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR(95%CI) = 0.71(0.63-0.81),0.88(0.79-0.97),0.68(0.56-0.82),and 0.72(0.61-0.85),respectively].A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR(95%CI) = 0.68(0.46-0.99)].In the summary estimates from casecontrol studies,all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk,whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies.The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design.There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer.展开更多
文摘A series of 4-thioflavonols compounds were synthesized by treating flavonols with lawsons reagent with variable substituent groups at A, B, and AB rings. All the synthesized compounds were checked for antibacterial and antifungal activity. We report that many compounds were found active against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, bacterial strains and, C. albicans, C. parapsilosisstrains and C. krusei fungal strains. Most of the synthesized 4-thioflavonols compounds were found to show enhanced antimicrobial activity than respective flavonol compounds.
文摘The cell cycle checkpoint system play a pivotal role in the cellular DNA damage response, and the discovery of checkpoint inhibitors is expected to sensitize current cancer therapies. Checkpoint signaling cascades are critically modulated by ATM (ataxia telangiectasia-mutated) and its related molecules. Generally, ATM primarily responds to ionizing irradiation-induced DNA double-strand breaks. Heavy ions from an accelerated carbon ion beam have been used to cure cancer because they are more effective than ionizing irradiation such as X-ray and γ-radiation in terms of biological damage. In a previous study, we demonstrated that a persimmon leaf flavonol (PLF) promoted the cytotoxic effect of chemotherapeutic agents on cancer cells through inhibition of checkpoint activities, especially in the ATM dependent pathway. The present study investigated whether PLF inhibits checkpoint activity during the DNA damage response induced by heavy ion irradiation. Treatment with PLF significantly increased the cytotoxicity of heavy ion irradiation in A549 adenocarcinoma cells. The phosphorylation of checkpoint proteins such as p53, SMC1, and Chk1 was increased by heavy ions. PLF reduced the phosphorylation of checkpoint proteins. Pre-treatment with PLF significantly prevented the decrease of mitotic cells in heavy ion-exposed cells. We further evaluated tumor volume in SCID mice inoculated with human lung adenocarcinoma A549 cells. The combination treatment of PLF and heavy ion resulted in a decrease of tumor volume compared with controls, although PLF itself did not exhibit any effect. These results indicate that PLF inhibits tumor growth through modulation of the DNA damage response. PLF may be useful for clinical application in combination with heavy ion radiotherapy.
文摘Flavonols were extracted from Acanthopanax Senticosus Harms by Soxhlet extraction（SE）,atmospheric pressure microwave-assisted extraction（AMAE） and pressurized microwave-assisted extraction（PMAE）.The influences of experimental conditions,such as concentration of ethanol in the eluent,microwave irradiation time,etc.on the extraction yield were studied.Four flavonols（hyperin,rutin,quercitrin and quercetin） in the extracts were determined quantitatively by HPLC method.The experimental results demonstrate the advantages of PMAE and AMAE over those of conventional SE,that is the extraction time is dramatically reduced,and the yields of flavonols are effective improved.Although the yield of flavonols is higher and the extraction time is shorter by PMAE than those of AMAE,flavonols are easy to be decomposed over a certain time.
文摘The enthalpies of bond dissociations of the hydroxyl groups, the energy of the highest occupied molecular orbitals and the corresponding radicals spin densities of all possible ten isomeric mono-hydroxyl flavones are calculated by means of 3-parameter Becke, Lee, Yang and Parr functional. The structural factors affecting these descriptors of radical-scavenging activity are outlined. The results obtained show that the hydroxyl groups in ring A and C are more involved in the process of a radical-capturing than recently believed.
文摘Hsp90 is a major protein involved in the stabilization of various proteins in cancer cells.The present investigation focused on the molecular docking simulation studies of flavanols as inhibitors of Hsp90 at the high affinity adenosine triphosphate（ATP）binding site and analyzed absorption,distribution,metabolism,excretion and toxicity（ADME-toxicity）.The molecular docking analysis revealed that the flavanols showed competitive inhibition with ATP molecule at the active site and enhanced pharmacological parameters.
基金Science and Technology Project of Gansu Province(grant No.18YF1NA128)the Natural Science Foundation of Liaoning Province(grant No.201602712).
文摘In this study,we designed a convenient method,to total synthesis of fl avonols especially for C-5 substituted ones and derivatives on a large scale.Beginning from the inexpensively available 2,4,6-trihydroxyacetophenone through Aldol condensation reaction,I2/DMSO cyclization reaction,Oxone“one pot”oxidation,kaempferol(1)and derivative(2)was obtained in an overall yield of 35%.The structures of the target compound and key intermediates were verifi ed by MS,IR,1H-NMR and 13C-NMR techniques,and the structure of 5a was further confi rmed by X-ray diff raction analysis.
基金supported by the Key Project for New Variety Breeding in Agriculture of Zhejiang Province,China(No.2021C02066-3)the Fundamental Research Funds for the Central Universities,China(No.226-2022-00215)the 111Project,China(No.B17039)。
文摘Flavonols and phenolic acids are key determinants of loquat nutritional quality,yet their inheritance remains unclear.In this study,high-performance liquid chromatography-photodiode array detector(HPLC-PDA)profiling of mature fruits from 95 F_(1)individuals derived from Tangkebaisha'×'Algerie'identified seven flavonol glycosides and two phenolic acids.Among these,quercetin 3-Ogalactoside(Q3Gal)and kaempferol 3-O-rhamnoside(K3Rha)were the most abundant flavonols,whereas neochlorogenic acid(5-CQA)dominated the phenolic acid fraction in both peel and flesh.All the traits exhibited wide transgressive segregation(coefficient of variation(CV),39.86%-81.48%).Notably,K3Rha,kaempferol 3-O-glucoside(K3Glc),quercetin 3-O-rutinoside,and chlorogenic acid in fruit pulp showed high transmission ability(>110%)and significantly better-parent heterosis(8.86%-88.56%),indicating strong potential for phenolic enrichment.Within the F_(1)population,line J-TAL-029 accumulated746.79μg/g fresh weight(FW)of total flavonols,and J-TAL-087 reached 3100.76μg/g FW of total phenolic acids,both substantially exceeding parental levels.Significant positive correlations were observed among flavonol glycosides sharing the same aglycone(e.g.K3Rha vs.K3Glc),indicating the feasibility of indirect selection for superior individuals.These findings elucidate the genetic basis of key phenolic compounds in loquat and provide a foundation for biofortification through breeding.
基金supported by the National Natural Science Foundation of China(32372667)。
文摘Flavonols and flavanones are important bioactive compounds with multiple pharmacological activities and health benefits.Transcriptional activation of flavonol and flavanone biosynthesis has been studied extensively,while little is known about the negative regulators.CRISPR/Cas9 gene-editing technology,with the advantage of precise genetic modification,is a desirable tool for breeding biofortified materials and exploring potential molecular mechanisms.In this study,a transcriptional repressor,Sl MYB32,was characterized in tomato fruit.Phenotype and metabolomic analyses confirmed that knockout of Sl MYB32 resulted in increased accumulation of flavonols and flavanones,especially about 1 mg g^(-1)FW of quercetin 3-O-rutinoside(rutin).Transcriptome analysis indicated that expression of key genes Sl PAL6,Sl4CL3 and Sl4CL4 as well as five candidate Sl UGTs were significantly up-regulated in slmyb32 mutants.Dual-luciferase and EMSA assays indicated Sl MYB32 could bind to and repress promoter activities of Sl PAL6 and Sl4CL3.Expression of 27 transcription factors belonging to 12 families was significantly changed in slmyb32 mutants,among which two Sl MYBs,two Sl NACs,two Sl AP2s and one Sl WRKY were clustered with known flavonoid regulators.Our results provide new insights into improving bioactive compounds in fruit and understanding negative regulatory mechanisms in flavonol and flavanone biosynthesis.
基金supported by Jiangsu Province Key Laboratory of Biomass Energy and Materials Basic Research Fund Project(JSBEM-S-202322)the National Key R&D Program of China(2022YFD1300903)the Research Supporting Project(RSP2023R352)of King Saud University,Riyadh,Kingdom.University,Riyadh,Saudi Arabia.
文摘In this study,we aimed to elucidate the mechanism of flavonol-Cu(Ⅱ)coordination binding to human serum albumin(HSA)and its effect on cellular activity,focusing on the regulation by the number of B-ring hydroxyl groups and Cu(Ⅱ)coordination.The number of B-ring hydroxyl groups was positively associated with fluorescence quenching ability,secondary structure modification,and protein affinity.The coordination of Cu(Ⅱ)altered the binding capacity,interaction,binding site,and binding kinetics between flavonols and proteins,as well as the secondary structure,fluorescence lifetime,and microscopic state of proteins.The number of B-ring hydroxyl groups was positively correlated with the ability of flavonols to inhibit HepG2 cell activity,and this correlation was not affected by Cu(Ⅱ)coordination.However,Cu(Ⅱ)binding weakened the ability of flavonols to inhibit HepG2 cell activity.This study contributes to a comprehensive understanding of how the number of hydroxyl groups in the B-ring of flavonols and the presence of copper ions affect their transport in the blood,providing new insights into the bioavailability of flavonols.
基金supported by the Key R&D Projects in Heilongjiang Province,China(GA21B012)the Collaborative Innovation Achievement Project of University in Heilongjiang Province,China(LJGXCG2022-040)。
文摘Flavonols possess significant medical value and are essential for plant stress resistance.These compounds constitute primary components of the nutritional value in onions,particularly in edible portions.While the flavonol biosynthetic pathway has been extensively studied,its regulatory mechanisms in onions remain incompletely understood.This investigation identified flavonol biosynthesis and regulatory genes through analysis of transcriptome and metabolomics data from different developmental stages of'SA1’.Two R2R3-MYB transcription factors,AcMYB12 and AcMYB29,were identified as positive regulators of onion flavonol biosynthesis.Transcriptional activation assays demonstrated that both could activate AcCHS,AcF3´H,and AcFLS.Yeast one-hybrid assays confirmed their direct binding to these gene promoters.The expression levels of flavonol pathway genes and flavonol contents in AcMYB12/AcMYB29-overexpressing onion calli and Arabidopsis plants were significantly higher than those in the control group.Transient silencing assays revealed partial functional redundancy between these two transcription factors.Notably,their regulatory capabilities exhibited significant differences.AcMYB12 predominantly regulates flavonol accumulation,while AcMYB29 specifically influences quercetin.Further investigation of the molecular mechanisms underlying differential regulation indicated variations in cis-elements within flavonol pathway gene promoters and differences in binding activity between transcription factors and cis-elements.
基金supported by the National Natural Science Foundation of China (31401820)the Natural Science Foundation of Jiangsu Province, China (BK20140702)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD130809001)the Fundamental Research Funds for the Central Universities (KJQN201538)
文摘Flavonols, the main flavonoids in plant leaves, have newly been proposed as a H2O2 scavenger in guard cells. However, whether 5-aminolevulinic acid(5-ALA) is involved in regulating stomatal movement of apple(Malus × domestica Borkh. ‘Fuji') leaves through flavonol accumulation remains unclear. In this study, using diphenylboric acid 2-amino ethyl ester(DPBA, a flavonol fluorescent dye) and a laser scanning confocal microscope,we observed that 5-ALA pretreatment significantly improved flavonol accumulation in guard cells of apple leaves, especially around the nucleus.Then we demonstrated that 5-ALA pretreatment inhibited ABA-induced stomatal closure via decreasing reaction oxygen species(ROS) accumulation in guard cells. Pretreatment with quercetin or kaempferol, two main kinds of flavonols in plants, also inhibited ABA-induced stomatal closure by decreasing ROS content in the guard cells. Furthermore, exogenous flavonols could suppress H2O2-induced stomatal closure in apple leaves.Taken together, we conclude that ALA-induced flavonol accumulation in guard cells is involved in the inhibitory effect of ALA on ABA-induced ROS accumulation and stomatal closure in apple leaves.
文摘In this research, supercritical carbon dioxide extraction （SFE） showed better extraction etlect when compared with Solid- liquid extraction （SLE）, Soxhlet extraction （SEt and Ultrasonic extraction （UE）, not only in the rate but also the time. The comparison among these three extraction modifiers, including acetone, ethanol and methanol demonstrated that ethanol was preferred to SFE due to its high extraction effect and low toxicology. In addition, parameter of SFE, influence of temperature and pressure were investigated, and the best extraction effect was achieved at the optima conditions, temperature of 40℃ and the pressure of 35 MPa. Thus, SFE is a highly effective method for flavonols extraction, requiring minimum energy and producing non-toxic byproduct. SFE-GC system is applied for the evaluation on flavonols that plays a key role in plant resistance to heavy metal, with its content and synthetase gene expression significantly increasing in plant when threatened by heavy metal. Besides, results indicated that flavonols can improve plant resistance to oxidative stress by quenching the redundant ROS in matrix.
基金Supported by National Key Technology R & D Program 2006BAD01A1701 and 2006BAD18B02Shandong Agriculture Good Cultivar Engineering Project (2008LZ09)~~
文摘[Objective]The aim was to identify the composition of pigments from Jujube fruit skin.[Method]Pigments were extracted from＇Lubei Dongzao＇,＇Lajiao Zao＇,＇Chengwu Dongzao＇,＇Dabailing＇and identificated by using high performance liquid chromatography-mass spectrometry（HPLC-MS）.[Result]The results showed that eight flavanols and four to five flavonols were detected,no anthocyanins was detected.The contents of flavonoids were differnt in four varieties.The contents of flavanols（11 mg/g） and flavonols（1.78 mg/g） in＇Dabailing＇ were one-time higher than other varieties.Quercetin 3 rutinoside was the major flavonol.[Conclusion]The research provided theoretical basis for further study on mechanism of Jujube pigment turnning into the red.
基金supports by the National Natural Science Foundation of China(No.22174037)the Joint Funds of the Hunan Provincial Natural Science Foundation of China(No.2023JJ50255)+1 种基金Changsha Science and Technology Project(No.Z202269490128)National Key Research and Development Program of China(No.2023YFF0613400)are appreciated.
文摘Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.
文摘Abstract： In the present study, we established an ultra performance liquid chromatography coupled with time-of-flight mass spectrometry （UPLC-QTOF-MSE） method to simultaneously quantify 33 components in Ginkgo biloba leaf extracts （GBEs）, including 17 flavonol glycosides, five terpene trilactones （TTLs）, four polyphenols and seven carboxylic acids. This optimized method was successfully applied to analyze the explicit compositions of GBE samples collected from different places. Furthermore, the data were processed through unsupervised principal component analysis （PCA） and supervised orthogonal partial least squared discrimination analysis （OPLS-DA） to evaluate the quality and compare the differences between the samples according to the contents of the 33 chemical constituents. Bilobalide, protocatechuic acid, shikimic acid, quinic acid, ginkgolide B, ginkgolide J, kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, quercetin-3-O-ct-L-rhamnopyranocyl-2＂-（6＇＂-p-coumaroyl）-β-D-glucoside and rutin were recognized as characteristic chemical markers that contributed most to control the quality of GBEs. Based on the fact that GBEs should be standardized with the characteristic components as quality control chemical markers, it is most important to maintain the quality of GBEs stable and reliable, and this method also provided a good strategy to further rectify and standardize the GBEs market.
文摘A phytochemical investigation on the leaves of Cistus parviflorus led to the isolation of 18 compounds.The structures of the isolated compounds were elucidated as kaempferol 3-O-（3′′,6′′-di-O-E-p-coumaroyl）-β-D-glucopyranoside（1）,scopoletin（2）,kaempferol 3-O-（3′′-O-E-p-coumaroyl）-β-D-glucopyranoside（3）,kaempferol 3-O-（6′′-O-E-p-coumaroyl）-β-D-glucopyranoside（4）,kaempferol 3-O-β-D-glucopyranoside（5）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-（6′-O-E-p-coumaroyl）-β-D-glucopyranoside（6）,methyl flavogallonate（7）,quercetin 3-O-β-D-glucopyranoside（8）,quercetin 3-O-β-D-galactopyranoside（9）,hydroquinone（10）,arbutin（11）,methyl β-glucopyranoside（12）,shikimic acid（13）,（S）-1,2-propandiol-1-O-β-D-glucopyranoside（14）,benzyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（15）,2-phenethyl-O-α-L-rhamnopyranosyl-（1→6）-β-D-glucopyranoside（16）,corchoionoside C（17）,kaempferol 3-O-α-L-rhamnopyranosyl-（1→2）-β-D-glucopyranoside（18） by the analysis of the MS and NMR spectroscopic data and comparison with the literature.Compounds 1–2,6–7,10–12,and 14–16 were isolated from Cistus genus for the first time.
基金Supported by Sao Paulo Research Foundation-FAPESP,No.2012-04634-1
文摘This review was based on a literature search of PubM ed and Scielo databases using the keywords "quercetin,rutin,isoquercitrin,isoquercitin(IQ),quercetin-3-glucoside,bioavailability,flavonols and favonoids,and cancer" and combinations of all the words.We collected relevant scientific publications from 1990 to 2015 about the absorption,bioavailability,chemoprevention activity,and treatment effects as well as the underlying anticancer mechanisms of isoquercitin.Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom.The subclass of flavonols receives special attention owing to their health benefits.The main components of this class are quercetin,rutin,and IQ,which is a flavonoid and although mostly found as a glycoside,is an aglycone(lacks a glycoside side chain).This compound presents similar therapeutic profiles to quercetin but with superior bioavailability,resulting in increased efficacy compared to the aglycone form.IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant,antiproliferative,anti-inflammatory,anti-hypertensive,and anti-diabetic.The protective effects of IQ in cancer may be due to actions on lipid peroxidation.In addition,the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway,mixed-lineage protein kinase 3,mitogen-activated protein kinase,apoptotic pathways,as well proinflammatory protein signaling.This review contributed to clarifying the mechanisms of absorption,metabolism,and actions of IQ and isoquercitrin in cancer.
基金supported by the European Union in the MSCA4Ukraine project ID Number 1232466.
文摘The fruits of the Sea buckthorn(Hippophae rhamnoides L.)are a popular plant food and a valuable health product.Cultivating plants produces a lot of leaves with fine branches as an unnecessary residue,which needs valorization.The aim of the study was to estimate(by HPLC-MS/MS)the qualitative and quantitative content of polyphenolic compounds in different parts of H.rhamnoides(HR),and to determine the level of antioxidant activity of leaves and fruits(by DPPH,ABTS methods and ferrozine test).Up to 19 compounds were identified in different parts of HR.The fruits are rich in flavonoids,including various glycosides of flavonols isorhamnetin,quercetin,and kaempferol.Two isorhamnetin glycosides were not identified in the leaves,while isorhamnetin-3-rhamnosylglactosides and the ellagitannins hippophaenin B,stachyurin and casuarinin were present only in the leaves of the plant.The bark and roots contained considerably more catechins,but minimal flavonols than the fruits and leaves of HR.The total phenolics and flavonols were most abundant in water infusions from leaves of HR(especially quercetin-3-O-glucoside-7-O-rhamnoside),compared to methanolic extracts.No significant differences in the quantitative and qualitative content of the fresh and dried leaves were detected.The highest antioxidant activity by all three methods was detected in the leaves of HR.In addition to the fruits,the leaves may have a perspective as a source of biologically active substances of HR.
文摘Flavonoids are widely used in industry for the prevention of various diseases. In daily life we are directly in touch with flavonoids due to their presence in different beverages, fruits and vegetables. Flavonoids are mainly used as a coloring agent in plants, antioxidant and nutritional food for human. Flavonoids have explicit role in UV filtration, symbiotic nitrogen fixation and floral pigmentation. Flavonoids have potential for different biological activities like chelation of metals, decreasing platelets aggregation and cell signaling etc.
文摘Stomach and colorectal cancers are common cancers and leading causes of cancer deaths.Because the alimentary tract can interact directly with dietary components,stomach and colorectal cancer may be closely related to dietary intake.We systematically searched published literature written in English via PubMed by searching for terms related to stomach and colorectal cancer risk and dietary flavonoids up to June 30,2012.Twenty-three studies out of 209 identified articles were finally selected for the analysis.Log point effect estimates and the corresponding standard errors were calculated using covariate-adjusted point effect estimates and 95%CIs from the selected studies.Total dietary flavonoid intake was not associated with a reduced risk of colorectal or stomach cancer [odds ratio(OR)(95%CI) = 1.00(0.90-1.11) and 1.07(0.70-1.61),respectively].Among flavonoid subclasses,the intake of flavonols,flavan-3-ols,anthocyanidins,and proanthocyanidins showed a significant inverse association with colorectal cancer risk [OR(95%CI) = 0.71(0.63-0.81),0.88(0.79-0.97),0.68(0.56-0.82),and 0.72(0.61-0.85),respectively].A significant association was found only between flavonols and stomach cancer risk based on a limited number of selected studies [OR(95%CI) = 0.68(0.46-0.99)].In the summary estimates from casecontrol studies,all flavonoid subclasses except flavones and flavanones were inversely associated with colorectal cancer risk,whereas neither total flavonoids nor any subclasses of flavonoids were associated with colorectal cancer risk in the summary estimates based on the cohort studies.The significant association between flavonoid subclasses and cancer risk might be closely related to bias derived from the case-control design.There was no clear evidence that dietary flavonoids are associated with reduced risk of stomach and colorectal cancer.
