ABSTRACT
Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3',4',7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases.
ABSTRACT
Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3',4',7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases.
ABSTRACT
Flavonoids are polyphenol compounds abundantly found in plants and reported to have an inhibitory effect on amyloidfibrillation. The number and position of hydroxyl groups, as well as the arrangement of flavonoids rings, may influencetheir inhibitory effects. In this study, we investigate the effect of structural characteristics of flavonoids on amyloid fibrilformation. For this purpose, five compounds (i.e., biochanin A, daidzein, quercetin, chrysin and fisetin) were selected thatrepresent a variety in the number and position of their hydroxyl groups. The inhibitory effect of these flavonoids on theamyloid fibril formation of apo-carbonic anhydrase (apo-BCA), as a model protein, was evaluated using thioflavin T andtransmission electron microscopy. The results showed that fisetin possessed the most significant inhibitory effect. Interestingly, upon apo-BCA acetylation, none of the tested flavonoids could inhibit the fibrillation process, which indicates thatthe interactions of these compounds with the amine groups of lysine residues could be somewhat important
ABSTRACT
Objective: To investigate the effect of fisetin (FIS) on foam cells by two-dimensional electrophoresis and mass spectrometry technology, and analyze the molecular mechanism of its inhibition. Methods: MTT method was used to detect the effect of ox-LDL on viability of RAW264.7 cells and fisetin on foam cells separately as well as chemical method was used to detect intracellular cholesterol ester, screening appropriate ox-LDL, and FIS concentration. Oil red O staining displayed accumulation of lipids changed by FIS in the foam cells. Then established proteomic maps of foam cells before and after treatment with FIS by bi-directional electrophoresis, mass spectrometry was adopted to identify differences in the expression of proteins. The expression of Cyt b5 was verified by Western blotting. Results: In our study, 20 μg/mL ox-LDL can successfully induce foam cells, as well as intervention of 100 μg/mL FIS would significantly decrease cholesterol ester and lipid accumulation within the foam cells. Proteomic experiment showed that foam cells treated by FIS had a lower expression of nuclear receptor, calreticulin and transcription elongation factor B, higher levels of glutathione S-transferase, cytochrome b5, Prelamin A/C, NADH dehydrogenase (ubiquinone) 2 flavin protein, lecithin-cholesterol acyltransferase, 78 kDa glucose regulation protein, supervillin, and heat shock protein 60. FIS can significantly improve the expression of Cyt b5 by WB. Conclusion: These data suggest that FIS can significantly inhibit foam cells formation by enhancing the cellular antioxidant and anti-inflammatory capabilities, reducing cellular stress response, as well as decreasing accumulation of intracellular cholesterol, regulation of apoptosis and enhanced immunity to prevent atherosclerosis.
ABSTRACT
AIM To prepare fisetin solid dispersions.METHODS Melting method and solvent method were used for the preparation of solid dispersions,respectively.With carrier type,drug-carrier ratio and stirring time as influencing factors,accumulative dissolution rate as an evaluation index,the preparation was optimized by orthogonal test on the basis of single factor experiment.The interaction between drug and carrier was investigated by Fourier transform infrared spectroscopy (FTIR),and the drug existing state was analyzed by differential scanning calorimetry (DSC).RESULTS Solvent method was more suitable for the preparation of solid dispersions.The optimal conditions were determined to be PVPK-30 as a carrier,1 ∶ 12 for drug-carrier ratio,and 30 min for stirring time,the accumulative dissolution rate reached 90.87％ within 20 min.There might be a hydrogen bond association between PVPK-30 and fisetin previously existing in amorphous or molecular state.CONCLUSION The dissolution rate of fisetin can be obviously increased after being prepared into solid dispersions.
ABSTRACT
O acidente vascular cerebral (AVC) é uma doença comum e uma das maiores causas de morte eincapacidade em todo o mundo. O acidente vascular cerebral isquêmico focal (AVCi) o corredevido a uma redução do aporte sanguíneo para uma região cerebral, levando ao decréscimo de oxigênio e glicose nos tecidos, induzindo a uma cascata de eventos, incluindo o estresse oxidativo e inflamação, que culminam com a morte neuronal e, com isso uma perda rápida da função neurológica. A Fisetina é um membro do subgrupo flavonol pertencente aos flavonoides,encontrado em diversas frutas e vegetais que apresentam propriedades antiinflamatórias e antioxidantes. O objetivo deste trabalho foi estudar os efeitos da Fisetina sobre o dano neuronal e memória, resposta inflamatória e sinaptogênese em camundongos submetidos ao modelo experimental de isquemia cerebral focal permanente (pMCAO). Os foram animais divididosentre os grupos falso-operados, tratados com veículo ou fisetina (FIS) na dose de 50 mg/kg,isquemiados tratados com veículo e isquemiados tratados com FIS nas doses de 10, 30, e 50mg/kg via oral, 3 horas depois da eletrocauterização da artéria cerebral média. O modelo deisquemia cerebral focal permanente foi comprovado através do aumento significativo da área de infarto e dos déficits sensório-motores nos animais isquemiados, observado através da coloração com TTC e da avaliação neurológica...
Stroke is a common disease and a major cause of death and disability worldwide. The focalischemic stroke (ischemic stroke) occurs due to a reduced blood supply to brain region,leading to the decrease of oxygen and glucose in tissues, inducing a cascade of eventsincluding oxidative stress and inflammation, culminating with neuronal death and thus a rapidloss of neurological function. Fisetin is a member of subgroup belonging to the flavonolflavonoid found in many fruits and vegetables that have anti-inflammatory and antioxidantproperties. The objective of this work was to study the effects of fisetin on neuronal damageand memory, inflammatory response and synaptogenesis in mice undergoing experimentalmodel of permanent focal cerebral ischemia (pMCAO). Were animals divided between thefalse-operated groups treated with vehicle or fisetin (SIF) at a dose of 50 mg / kg-ischemictreated with vehicle and-ischemic treated with FIS in doses of 10, 30, and 50 mg / kg po 3hours after the middle cerebral artery electrocautery. The permanent focal cerebral ischemiamodel was proven by the significant increase in infarct area and sensorimotor deficits inischemicanimals, observed by staining with TTC and neurological evaluation...
Subject(s)
Humans , Inflammation , Plants, MedicinalABSTRACT
Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane A2- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.
Subject(s)
Animals , Humans , Male , Rats , Fluorides , Fruit , Isometric Contraction , Muscle, Smooth, Vascular , Nitric Oxide , Phosphorylation , Relaxation , rho-Associated Kinases , VegetablesABSTRACT
Natural polyphenols are major constituents of plant foods and herbs. Numerous reports demonstrated that these compounds inhibited amyloid formation and destabilized the preformed amyloid fibrils. The present study, utilizing bovine insulin as a model peptide, examined the antiamyloidogenic effects of fisetin (3,7,3',4'-tetrahydroxyflavone). Fluorescent probes, transmission electron microscopy and hemolytic assay were utilized to determine the roles of fisetin on amyloidogenesis of insulin. The results demonstrated that fisetin dose-dependently inhibited amyloid formation of insulin. Moreover, fisetin disaggregated the preformed insulin fibrils and transformed the fibrils into non-amyloid structures. Hemolysis was observed when erythrocytes were co-incubated with insulin fibrils. Fisetin inhibited fibril-induced hemolysis in a dose-dependent manner. Hydrophobic interaction is suggested to be a key driving force in the anti-amyloidogenic and fibril-disaggregating effects of fisetin. The results of the present work suggest that fisetin is an effective anti-amyloidogenic compound and may serve as a lead structure for the design of novel drugs for the treatment of amyloid diseases.
ABSTRACT
Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-alpha, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-kappaB. In agreement, the upstream phosphorylation events for NF-kappaB activation, composed of Src, Syk, and IkappaBalpha, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.
Subject(s)
Flavonoids , Immunoblotting , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase , Phosphorylation , Phosphotransferases , Plants , Prostaglandin-Endoperoxide Synthases , RNA, Messenger , Tumor Necrosis Factor-alphaABSTRACT
Rat models of diabetes were established by injecting streptozocin intraperitoneally.According to random number table,three groups were divided:normal group,diabetic group,and fisetin-treated group.After 24 weeks,all rats were sacrificed.Biochemical parameters of blood and urine samples were tested.The pathological changes were observed by paraffin sections staining with HE.The expression of extracellular matrix proteins was analyzed via PAS and Masson staining.Location of p300 protein expression was analyzed by immunohistochemistry.The protein expressions of p300 and MMP-2 were determined by Western blotting.The mRNA expressions of MMP-2 were analyzed via real-time PCR.The biochemical parameters and kidney pathological images in fisetin-treated group were better than those in diabetic group.The expression of extraeellular matrix proteins was lower than that in diabetic group.Immunohistochemistry analysis showed that among three groups the expression of p300 was mainly in glomeruli,and was also expressed in cell nucleus and cytoplasm and the coloration of fisetin-treated group was weakened as compared with diabetic group.Western blotting analysis showed that the expression of p300 protein in fisetin-treated group was lower than that in diabetic group(P＜O.05).The expressions of MMP-2 mRNA and MMP-2 protein were higher than those in diabetic group (P ＜ 0.05).It is suggested that fisetin may attenuate diabetes associated abnormalities in the kidney of rats,owing probably to inhibiting the expressions of p300 and enhancing the expressions of MMP-2.
ABSTRACT
Ionizing radiation can induce cellular oxidative stress through the generation of reactive oxygen species, resulting in cell damage and cell death. The aim of this study was to determine whether the antioxidant effects of the flavonoid fisetin (3,7,3',4'-tetrahydroxyflavone) included the radioprotection of cells exposed to gamma-irradiation. Fisetin reduced the levels of intracellular reactive oxygen species generated by gamma-irradiation and thereby protected cells against gamma-irradiation-induced membrane lipid peroxidation, DNA damage, and protein carbonylation. In addition, fisetin maintained the viability of irradiated cells by partially inhibiting gamma-irradiation-induced apoptosis and restoring mitochondrial membrane potential. These effects suggest that the cellular protective effects of fisetin against gamma-irradiation are mainly due to its inhibition of reactive oxygen species generation.
Subject(s)
Antioxidants , Apoptosis , Cell Death , DNA Damage , Lipid Peroxidation , Membrane Potential, Mitochondrial , Membranes , Oxidative Stress , Protein Carbonylation , Radiation, Ionizing , Reactive Oxygen SpeciesABSTRACT
ObjectiveTo explore the effects of fisetin on the learning and memory abilities impairments induced by Aβ in mice.MethodsAlzheimer's disease (AD) animal model was made by single intracerebroventricular infusion of Aβ (1-42) through guide cannula.Fisetin was orally administered 7 days before Aβ infusion once a day,and continued throughout the experimental period.Water maze test began on day 3 after Aβ infusion.All mice were sacrificed and hippocampi were dissected immediately after behavioral test.The protein expression of hippocampal nuclear Nrf2 and the mRNA level of HO-1,GCLC and GCLM were examined by western blotting and RT-RCR techniques respectively.Results ( 1 ) Aβ (1-42) significantly increased escape latency in hidden platform test ( (25.4 ± 3.33 ) s ),and decreased the number of crossings in probe test ( 1.70 ± 0.25 ) compared with control ((9.05 ± 1.37 )s) for hidden plat form ;4.50 ± 0.41 for probe test) and Aβ (42-1)-treated group ( ( 10.80 ± 1.38)s) for hidden platform test; 4.10 ±0.39 for probe test; P＜0.01 ).The prolonged treatment with fisetin dose-dependently reversed the changes (10 mg/kg:17.54 ± 3.56s for hidden platform test;2.50 ± 0.40 for probe test,P＜0.05,20 mg/kg:( 13.04 ± 2.36) s for hidden platform test;3.60 ±0.36 for probe test,P＜0.01 ).(2) Aβ (1-42) significantly decreased the nuclear Nrf2 protein level (0.07 ±0.02),and mRNA level (0.45 ±0.04) of HO-1,GCLC (0.41 ± 0.04) and GCLM (0.26 ± 0.03 ) in the hippocampus of mice compared with control (0.18 ± 0.02 for Nrf2 ;0.83 ± 0.09 for HO-1 ; 1.01 ± 0.10 for GCLC; 0.65 ± 0.07 for GCLM) and Aβ (42-1 ) -treated group (0.21 ± 0.02 for Nrf2 ; 0.90 ± 0.08 for HO-1 ; 1.11 ± 0.11 for GCLC ; 0.72 ± 0.07 for GCLM) ( P ＜ 0.05 or P ＜ 0.01 ).However,fisetin administration significantly counteracted these changes ( 10 mg/kg:0.11± 0.01 for Nrf2 ; 0.56 ± 0.06 for HO-1 ; 0.61 ± 0.04 for GCLC ; 0.35 ± 0.04 for GCLM ; 20 mg/kg:0.16 ± 0.02for Nrf2;0.79±0.10 for HO-1;0.86±0.09 for GCLC;0.51±0.04 for GCLM;P＜0.05).ConclusionFisetin attenuates learning and memory impairments induced by Aβ (1-42) through activation of Nrf2 antioxidant signaling pathway.