Role Of Flavonoids Research Articles

CURRENT EPIDEMIOLOGICAL KNOWLEDGE ABOUT THE ROLE OF FLAVONOIDS IN PROSTATE CARCINOGENESIS

Numerous experimental studies have demonstrated anticancer action of polyphenolic plant metabolites. However, data about associations between dietary intake of plant-derived flavonoids and prostate cancer risk are still sparse and inconsistent. This minireview compiles the epidemiological findings published to date on the role of flavonoids in prostate tumorigenesis, discusses the reasons of inconsistencies and elicits the promising results for chemoprevention of this malignancy. Long-term consumption of high doses of soy isoflavones can be the reason of markedly lower clinically detectable prostate cancer incidence among Asian men compared to their counterparts in the Western world. The ability to metabolize daidzein to equol, the most biologically active isoflavone, by the certain intestinal bacteria also seems to contribute to this important health benefit. The increasing incidence rate of prostate cancer related to adoption of westernized lifestyle and dietary habits makes the issue of chemoprevention ever more important and directs the eyes to specific food components in the Eastern diet. If further large-scale epidemiological studies will confirm the protective effects of isoflavones against prostate cancer, this could provide an important way for prostate cancer prevention, as diet is a potentially modifiable factor in our behavioral pattern.

ACYLATED FLAVONOIDS OF SPIRAEA GENUS AS α-AMYLASE INHIBITORS

Spiraea L. is a genus of deciduous shrubs of Rosaceae family widespread on the territory of Eastern Siberia. As a result of the study of six Spiraea species growing on the Baikal region, it was shown that they characterized by a high content of phenolic compounds and their extracts had an inhibitory effect on α-amylase. The use of correlation analysis made it possible to reveal the leading role of flavonoids as carriers of the biological effect of extracts. The most active was the extract of S. salicifolia leaves with an IC50 value 69,30 μg/mL After fractionation and chromatographic separation of the extractive substances, 18 compounds were isolated from the ethyl acetate fraction of S. salicifolia and fifteen of them for the first time for the species, including trifolin, 6′′-O-caffeoyl-hyperoside, 6′′-O-caffeoyl-isoquercitrin, 6′′-O-caffeoyl-astragalin, 1-O-p-hydroxybenzoyl-6-O-p-coumaroyl-β-d-glucopyranoside, 3,4,5-tri-O-caffeoylquinic acid, isoramnetinin-3-O-β-d-glucopyranoside, tiliroside, isoramnetin-3-O-α-l-rhamnopyranoside, 1-O-cis-cinnamoyl-6-O-(2′-methylene-4′-hydroxybutyroyl)-β-d-glucopyranose, 1-О-(4′′-hydroxy-3′′-methylfurane-2′′-one)-6-О-trans-cinnamoyl-β-d-glucopyranose, 1-О-(4′′-hydroxy-3′′-methylfurane-2′′-one)-6-О-cis-cinnamoyl-β-d-glucopyranose, 6-tuliposide A and tulipalin A. The most active inhibitors of α-amylase were flavonoid caffeoyl glycosides with 6′′-O-caffeoyl-hyperoside as a most effective inhibitor with IC50 value 46.18 μg/mL. Latter compound determined the total anti-α-amylase effect of S. salicifolia. The content of 6′′-O-caffeoyl-hyperoside in leaves of S. salicifolia was 0,60-10,53 mg/g and flavonoids – 12,02-23,17 mg/g. This study demonstrated the fact that the acylated flavonoids of Spiraea are effective inhibitors of α-amylase.

Role of flavonoids and nitrates in cardiovascular health.

CVD remain the leading cause of death globally. Effective dietary strategies for their reduction are of high priority. Increasing evidence suggests that phytochemicals, particularly dietary flavonoids and nitrates, are key modulators of CVD risk reduction through impact on multiple risk factors. The aim of this review is to explore the evidence for the impact of flavonoid- and nitrate-rich foods and supplements on CVD risk, with specific reference to their importance as mediators of vascular health and platelet function. There is accumulating evidence to support benefits of dietary flavonoids on cardiovascular health. Dose-dependent recovery of endothelial function and lowering of blood pressure have been reported for the flavanol (-)-epicatechin, found in cocoa, apples and tea, through production and availability of endothelial nitric oxide (NO). Furthermore, flavonoids, including quercetin and its metabolites, reduce in vitro and ex vivo platelet function via inhibition of phosphorylation-dependent cellular signalling pathways, although further in vivo studies are required to substantiate these mechanistic effects. Hypotensive effects of dietary nitrates have been consistently reported in healthy subjects in acute and chronic settings, although there is less evidence for these effects in patient groups. Proposed mechanisms of actions include endothelial-independent NO availability, which is dependent on the entro-salivary circulation and microbial conversion of dietary nitrate to nitrite in the mouth. In conclusion, flavonoid- and nitrate-rich foods show promising effects on vascular function, yet further randomly controlled studies are required to confirm these findings and to determine effective doses.

Role of Flavonoids in DNA Damage and Carcinogenesis Prevention

High level of ionizing radiation and various other mutagenic agents can damage DNA and induce carcinogenesis which may be transferred to offspring’s. Flavonoids are major antioxidant compounds obtained from plants and form a significant proportion of most diets. In this review, we have summarized the present understanding of the roles of various flavonoids as preventive approaches against DNA damage and carcinogenesis.

The Role of Flavonoids in Nodulation Host-Range Specificity: An Update.

Flavonoids are crucial signaling molecules in the symbiosis between legumes and their nitrogen-fixing symbionts, the rhizobia. The primary function of flavonoids in the interaction is to induce transcription of the genes for biosynthesis of the rhizobial signaling molecules called Nod factors, which are perceived by the plant to allow symbiotic infection of the root. Many legumes produce specific flavonoids that only induce Nod factor production in homologous rhizobia, and therefore act as important determinants of host range. Despite a wealth of evidence on legume flavonoids, relatively few have proven roles in rhizobial infection. Recent studies suggest that production of key “infection” flavonoids is highly localized at infection sites. Furthermore, some of the flavonoids being produced at infection sites are phytoalexins and may have a role in the selection of compatible symbionts during infection. The molecular details of how flavonoid production in plants is regulated during nodulation have not yet been clarified, but nitrogen availability has been shown to play a role.

Impacts of simulated drought stress and artificial damage on concentrations of flavonoids in Jatropha curcas (L.), a biofuel shrub.

We studied the possible roles of flavonoids in the antioxidant and antiherbivore chemistry in Jatropha curcas (L.), a Latin American shrub that holds great potential as a source of biofuel. Changes in flavonoid concentrations in the leaves of J. curcas seedlings exposed to artificial damage and to different rainfall patterns were assessed by applying a 32-factorial experiment in a greenhouse. The concentrations of different flavonoids in the leaves of seedlings were significantly affected by interaction effects of artificial damage, drought stress and age of the seedling. The highest flavonoid concentrations were obtained in seedlings imposed to the highest percentage of artificial damage (50%) and grown under extreme drought stress (200mmyear-1). In this treatment combination, flavonoid concentrations were three-fold as compared to seedlings exposed to the same level of artificial damage but grown in 1900mmyear-1 rainfall application. Without artificial damage, the concentration of flavonoids in the seedlings grown in 200mmyear-1 rainfall application was still two-fold compared to seedlings grown in higher (>800mmyear-1) rainfall applications. Thus, the observed flavonoid concentration patterns in the leaves of J. curcas seedlings were primarily triggered by drought stress and light rather than by artificial damage, suggesting that drought causes oxidative stress in J. curcas.

The Possible Role of Flavonoids in the Prevention of Diabetic Complications

Type 2 diabetes mellitus is a disease that affects many metabolic pathways. It is associated with insulin resistance, impaired insulin signaling, β-cell dysfunction, abnormal glucose levels, altered lipid metabolism, sub-clinical inflammation and increased oxidative stress. These and other unknown mechanisms lead to micro- and macro-complications, such as neuropathy, retinopathy, nephropathy and cardiovascular disease. Based on several in vitro animal models and some human studies, flavonoids appear to play a role in many of the metabolic processes involved in type 2 diabetes mellitus. In this review, we seek to highlight the most recent papers focusing on the relationship between flavonoids and main diabetic complications.

Role of dietary flavonoids in amelioration of sugar induced cataractogenesis

Sugar induced cataractogenesis and visual impairment is more prominent ophthalmic problem in humans suffering from diabetes. Flavonoids have been identified as one of the therapeutically important class of phytochemicals possessing myriad of biological activities. Analyzing the anti-cataract effects of flavonoids from natural sources is an important aspect owing to their bioavailability in variety of dietary sources. In the present study a panel of ten dietary flavonoids like 3, 6-dihydroxy flavone, 3, 7-dihydroxy flavone, chrysin, 3-hydroxy-7-methoxy flavone, apigenin, genistein, baicalein, galangin, Biochanin-A, and diosmin were evaluated for their anti-cataract effects in sugar induced lens model studies. Series of parameters like role of flavonoids in glycation induced lens opacity, protein aggregation measurements, carbonyl group formation: a biochemical marker of glycation reaction, non-tryptophan fluorescence: a marker of formation of advanced glycation end products (AGEs) and assessment of (experimental and in silico) aldose reductase inhibition: a key enzyme of polyol pathway involved in cataractogenesis. The results of the study clearly demonstrated the impressive anti-cataract activity of chrysin followed by significant activity by apigenin, baicalein and genistein. The results of the present study may find applications in formulation of functional foods and neutraceuticals for the management of diabetic cataract.

Biogenic approaches using citrus extracts for the synthesis of metal nanoparticles: the role of flavonoids in gold reduction and stabilization

Experimental and theoretical data support the easy reduction of Au3+ into self-stabilized nanoparticles by citrus flavonoids.

Effect of Nitrogen Fertilization and Harvest Time on Steviol Glycosides, Flavonoid Composition, and Antioxidant Properties in Stevia rebaudiana Bertoni.

This work investigated the effect of nitrogen fertilization and harvest time on the flavonoid composition and antioxidant properties of Stevia rebaudiana leaves. At the same time, changes in stevioside (Stev) and rebaudioside A (RebA) contents were recorded. A pot trial under open air conditions was set up, testing five N rates and three harvest times. The results showed that, by using an adequate N rate and choosing an appropriate harvest time, it was possible to significantly increase and optimize the bioactive compound levels. In particular, higher RebA, RebA/Stev ratio, total phenols and flavonoids, luteolin-7-O-glucoside, and apigenin-7-O-glucoside levels and antioxidant capacity were recorded by supplying 150 kg N ha(-1). Reduced or increased N availability in comparison with N150 had no consistent effect on Stevia phytochemicals content. Significant correlations were also found between stevioside and some of the flavonoids, indicating a possible role of flavonoids in the stevioside metabolic pathway, which deserves more investigations.

Role of flavonoids in future anticancer therapy by eliminating the cancer stem cells.

Despite the numerous recent advances made in conventional anticancer therapies, metastasis and recurrence still remain the major problems in cancer management. The current treatment modalities kill the bulk of the tumor, leaving cancer stem cells behind and therefore, the agents specifically targeting this cancer initiating cell population may have important clinical implications. In this review article, the data about the inhibitory action of flavonoids, both natural as well as their synthetic derivatives, on the self-renewal capacity and survival of cancer stem cells of different origins are compiled and analyzed. These data indicate that several plant secondary metabolites, including soy isoflavone genistein, green tea catechins and a widely distributed flavonol quercetin, have the potential to suppress the stemness markers and properties, traits of the epithelial-to-mesenchymal transition and migratory characteristics, being also able to sensitize these cells to the standard chemotherapeutic drugs. These polyphenolic compounds act through multiple signal transduction pathways, providing thus the maximal therapeutic response and offering some promise to be included in the future cancer treatment schemes in combination with the conventional therapies. Such approach may give an important contribution to the shift of cancer management from palliative to curative mode, likely leading to the disease-free survival. Thus, flavonoids can serve as attractive candidates for novel anticancer agents by eliminating the roots of cancer.

Potential ecological roles of flavonoids from Stellera chamaejasme

Stellera chamaejasme L. (Thymelaeaceae), a perennial weed, distributes widely in the grasslands of Russia, Mongolia and China. The plant synthesizes various secondary metabolites including a group of flavonoids. To our knowledge, flavonoids play important roles in the interactions between plants and the environment. So, what are the benefits to S. chamaejasme from producing these flavonoids? Here, we discuss the potential ecological role of flavonoids from S. chamaejasme in protecting the plant from insects and other herbivores, as well as pathogens and competing plant species, and new data are provided on the phytotoxicity of flavonoids from S. chamaejasme toward Poa annua L.

The role of flavonoids on oxidative stress in epilepsy.

Backgrounds. Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects. Objective. This review provides an overview about the role of flavonoids in oxidative stress in epilepsy. The mechanism of action of flavonoids and its relation to the chemical structure is also discussed. Results/Conclusions. There is evidence that suggests that flavonoids have potential for neuroprotection in epilepsy.

Preventive role of Indian black pepper in animal models of Alzheimer's disease.

Dementia is the clinical symptom of alzheimer's disease. Brain cholinesterase levels and behavioural changes are the markers for Alzheimer's disease and aluminium chloride is one causative agent for polymerization of tau protein and amyloid plaque formation in Alzheimer's disease. Effect of piper nigrum and its role in prevention of alzhimer's disease and symptoms are well linked in this study. To study the effect of piper nigrum for the prevention of alzheimer's associated histopathological, biochemical and behaviour changes in rat model. Twenty four rats were taken in this study. Their baseline behavioural parameters were noted and group was separated randomly in four. Rats were pretreated with piper nigrum and Alzheimer's disease was induced. Biochemical and histopathological changes were noted at the end of experiment. There was marked decrease in cholinesterase level, amyloidal plaque formation in rats brain who were pretreated with piper nigrum. At the same time there was decrease in escape latency time (ELT) and increase in memory in piper treated rats. Piper nigrum prove to be effective for prevention of Alzheimer's disease. This finding has to be confirmed with studies including larger population. Further research on cholinesterase inhibitors, role of flavonoids on prevention of neurodegeneration in Alzheimer's disease can be encouraged.

Flavonoids of Echinps latifolius suppress Wnt signaling in adjuvant arthritis rats

The role of flavonoids of Echinps latifolius (FELT) in Wnt signaling was investigated in adjuvant arthritis (AA) rats. The therapeutic effects of FELT on AA rats were detected by rat arthritis score and MTT. The effect of FELT gavage treatment on the Wnt signaling key gene β-catenin, C-myc and cyclin D1 in synovium from AA rats was detected by Real-time qPCR, and the effects of FELT gavage treatment on the upstream negative regulation gene SFRP 1,2,4,5 in synovium from AA rats were detected by Real-time qPCR. The results showed that FELT gavage treatment significantly inhibited arthritis score and MTT values in AA rats, significantly inhibited the expression of the Wnt signaling gene β-catenin, C-myc and cyclin D1, significantly up-regulated the expression of the up- stream negative regulation gene SFRP 1,2,4. FELT has a better therapeutic effect for AA rats.

Methyl-methoxylpyrrolinone and flavinium nucleus binding signatures on falcipain-2 active site.

Following the increasing reports of human toxicity and plasmodium resistance to artemisinin and its derivatives, falcipain-2 (FP-2) is now emerging as the choice antimalarial drug target. Coincidentally, FP-2 is the in vivo target of naturally occurring, therapeutically safe flavonoids (stenopalustroside, myricetin, and fisetin) and symplostatin (symplostatin 4) compounds known to exhibit potent in vitro and in vivo antiplasmodial actions. Here, the structural bases for their inhibitory actions have been studied using molecular dynamics simulation. Myricetin and fisetin act as proton transfer tunnel breakers by inserting between His174 and Cys42, which are key active site residues of FP-2, stenopalustroside inhibits the polarization of His174 by Asn173; a major preparatory step for Cys42/His174 proton transfer process. The roles of flavonoids are favored by T-shaped pi-pi interactions with His174. Symplostatin 4 inserts its methyl-methoxylpyrrolinone moiety into the active site where its proton acceptor function prepares Cys42 for nucleophilic attack on the Michael α,β-unsaturated bonds on its 4(S)-amino-2(E)-pentenoate moiety. Further analyses of the structures identified a unique bridge formed on FP-2 active site groove by stenopalustroside and symplostatin 4 during interaction with the sub-site I of FP-2, whereas fisetin preferentially interacts with sub-site II and myricetin interacts with sub-site III residues. Ultimately, symplostatin-4, myricetin, and fisetin were better than stenopalustroside at trapping FP-2 in its inactive state as revealed by comparative RSMD plots with X-ray structures of FP-2 co-crystallized with inhibitors. Comparative estimates of free energy of binding using the Molecular Mechanics-Poisson Boltzmann Surface Area (MMPBSA) method suggested that His174 protonation may further enhance stenopalustroside-FP-2 interaction. The unique binding signatures of the ligands within the FP-2 active site groove and its sub-sites may explain the subtle differences in their IC50 values and their mechanism of inhibition.

Beyond Organoleptic Characteristics: The Pharmacological Potential of Flavonoids and their Role in Leukocyte Migration and in L‐Selectin and β2‐Integrin Expression During Inflammation

Flavonoids are compounds responsible for several organoleptic characteristics of plant-derived foods. They are also bioactive compounds with antiinflammatory role. Different mechanisms for this activity have been reported, but their effects on cell migration are not fully understood. In the present study, the role of flavonoids on leukocyte migration in vivo was investigated, using the carrageenan-induced pleurisy model and intravital microscopy in rats. It was found that quercetin (1), rutin (2), flavone (5), apigenin (6) and flavonol (7) reduced cell migration to the pleural cavity and inhibited rolling, adhesion and transmigration. Additionally, flow cytometry assays showed that the in vitro treatment with all compounds (15-60 µM) did not cause cell death and 1 inhibited the cleavage of L-selectin and the β2-integrin expression, whereas 2 and 7 only inhibited the β2-integrin expression. Together, data herein presented clearly show the ability of flavonoids to inhibit in vivo neutrophil influx into inflamed tissue, by acting in different mechanisms of neutrophil migration.

The role of flavonoids in false positive digoxin assays caused by the consumption of hibiscus flower and rose hip tea

The role of flavonoids in false positive digoxin assays caused by the consumption of hibiscus flower and rose hip tea

Role of flavonoids on oxidative stress and mineral contents in the retinoic acid-induced bone loss model of rat

Reactive oxygen species play a role in a number of degenerative conditions including osteoporosis. Flavonoids as phyto-oestrogens exert physiological effects against oxidative stress diseases. We developed a retinoic acid-induced bone loss model of rats to assess whether flavonoids and alendronate as positive control have role against oxidative stress and mineral contents in osteoporosis in vivo. Three-month-old female rats of the Y59 strain were given quercetin, chrysin, naringenin (100 mg kg(-1)) or alendronate (40 mg kg(-1), a positive control) immediately before retinoic acid treatment (80 mg kg(-1)) once daily for 14 days by a single intragastric (i.g.) application. In the second part of the study, we assessed the effect of those flavonoids on the skeletal system of healthy rats using single i.g. application on the respective flavonoids during 14 days. Twenty-four hours after the treatment, we analysed bone mineral density and the total content of bone calcium and phosphorus in the femur, the geometric and physical characteristics of thigh bones and lipid peroxidation and glutathione levels of liver and kidney cells. All flavonoids improved the decrease in bone weight coefficient, the length and the diameter of the bone, the content of bone ash and calcium and phosphorus content induced by retinoic acid. Chrysin and quercetin showed promise as preventive agents. Flavonoids were superior to alendronate according to some criteria. These results suggest that the dietary flavonoids could reduce retinoic acid-induced oxidative stress and bone loss and that flavonoids may be useful therapeutics for prevention of skeletal diseases.

Involvement of kaempferol in the defence response of virus infected Arabidopsis thaliana

The roles of several phenolic compounds in plant defence response have been extensively studied, yet little is known about the role of flavonoids in plant-virus interaction. Quantitative and qualitative changes of selected phenolics in Arabidopsis thaliana induced by Cucumber mosaic virus containing satellite RNA (CMVsat) infection were analysed accompanied by plant hormone, chalcone synthase and pathogenesis-related gene expression analysis. Lower leaves of infected plants had a lower concentration of total phenolics compared to control plants. The concentration of kaempferol in upper leaves of all infected plants was significantly lower compared to control plants, while the expression of the chalcone synthase gene in those leaves was in most cases upregulated. All infected plants had a higher concentration of indole-3-acetic acid in lower leaves, which was accompanied with a lower concentration of kaempferol in upper leaves. Our research demonstrates a correlation between kaempferol and indole-3-acetic acid in response to CMVsat infection in Arabidopsis. We demonstrated two different metabolic patterns in infected plants suggesting the activation of two different defence responses. We also propose kaempferol to be an important part of the auxin-dependent defence response which limits systemic movement of CMVsat and that this defence response is activated prior to the well-known salicylic acid dependent defence response. Further research on kaempferol and its role in Arabidopsis-CMVsat interaction will improve our understanding on the role of flavonoids in plant defence.