Stress-responsive dihydroxy B-ring-substituted flavonoids have great potential to inhibit the generation of reactive oxygen species (ROS) and reduce the levels of ROS once they are formed, i.e., to ...perform antioxidant functions. These flavonoids are located within or in the proximity of centers of ROS generation in severely stressed plants. Efficient mechanisms have been recently identified for the transport of flavonoids from the endoplasmic reticulum, the site of their biosynthesis, to different cellular compartments. The mechanism underlying flavonoid-mediated ROS reduction in plants is still unclear. ‘Antioxidant’ flavonoids are found in the chloroplast, which suggests a role as scavengers of singlet oxygen and stabilizers of the chloroplast outer envelope membrane. Dihydroxy B-ring substituted flavonoids are present in the nucleus of mesophyll cells and may inhibit ROS-generation making complexes with Fe and Cu ions. The genes that govern the biosynthesis of antioxidant flavonoids are present in liverworts and mosses and are mostly up-regulated as a consequence of severe stress. This suggests that the antioxidant flavonoid metabolism is a robust trait of terrestrial plants. Vacuolar dihydroxy B-ring flavonoids have been reported to serve as co-substrates for vacuolar peroxidases to reduce H2O2 escape from the chloroplast, following the depletion of ascorbate peroxidase activity. Antioxidant flavonoids may effectively control key steps of cell growth and differentiation, thus acting regulating the development of the whole plant and individual organs.
Female hop cones are used extensively in the brewing industry, but there is now increasing interest in possible uses of hops for non-brewing purposes, especially in the pharmaceutical industry. Among ...pharmaceutically important compounds from hops are flavonoids, having proven anticarcinogenic, antioxidant, antimicrobial, anti-inflammatory and estrogenic effects. In this review we aim to present current knowledge on the biotransformation of flavonoids from hop cones with respect to products, catalysis and conversion. A list of microbial enzymatic reactions associated with gastrointestinal microbiota is presented. A comparative analysis of the biological activities of hop flavonoids and their biotransformation products is described, indicating where further research has potential for applications in the pharmaceutical industry.
•Hops are not only a basic brewing raw material, but extracts can be used as health remedies•Many hop flavonoids and their biotransformation products have proven biological activities–anticarcinogenic, antioxidant, antimicrobial, anti-inflammatory and estrogenic effects.•There are many biotransformation reactions applicable to hop flavonoids, resulting in many new molecules with different biological activities.•Biotransformation reactions of flavonoids can be applied in the pharmaceutical industry.
Epidemiologic studies demonstrate inverse associations between flavonoid intake and chronic disease risk. However, lack of comprehensive databases of the flavonoid content of foods has hindered ...efforts to fully characterize population intakes and determine associations with diet quality.
Using a newly released database of flavonoid values, this study sought to describe intake and sources of total flavonoids and 6 flavonoid classes and identify associations between flavonoid intake and the Healthy Eating Index (HEI) 2010.
One day of 24-h dietary recall data from adults aged ≥ 20 y (n = 5420) collected in What We Eat in America (WWEIA), NHANES 2007-2008, were analyzed. Flavonoid intakes were calculated using the USDA Flavonoid Values for Survey Foods and Beverages 2007-2008. Regression analyses were conducted to provide adjusted estimates of flavonoid intake, and linear trends in total and component HEI scores by flavonoid intake were assessed using orthogonal polynomial contrasts. All analyses were weighted to be nationally representative.
Mean intake of flavonoids was 251 mg/d, with flavan-3-ols accounting for 81% of intake. Non-Hispanic whites had significantly higher (P < 0.001) intakes of total flavonoids (275 mg/d) than non-Hispanic blacks (176 mg/d) and Hispanics (139 mg/d). Tea was the primary source (80%) of flavonoid intake. Regardless of whether the flavonoid contribution of tea was included, total HEI score and component scores for total fruit, whole fruit, total vegetables, greens and beans, seafood and plant proteins, refined grains, and empty calories increased (P < 0.001) across flavonoid intake quartiles.
A new database that permits comprehensive estimation of flavonoid intakes in WWEIA, NHANES 2007-2008; identification of their major food/beverage sources; and determination of associations with dietary quality will lead to advances in research on relations between flavonoid intake and health. Findings suggest that diet quality, as measured by HEI, is positively associated with flavonoid intake.
• Background New roles for flavonoids, as developmental regulators and/or signalling molecules, have recently been proposed in eukaryotic cells exposed to a wide range of environmental stimuli. In ...plants, these functions are actually restricted to flavonols, the ancient and widespread class of flavonoids. In mosses and liverworts, the whole set of genes for flavonol biosynthesis - CHS, CHI, F3H, FLS and F3'H - has been detected. The flavonol branch pathway has remained intact for millions of years, and is almost exclusively involved in the responses of plants to a wide array of stressful agents, despite the fact that evolution of flavonoid metabolism has produced > 10 000 structures. • Scope Here the emerging functional roles of flavonoids in the responses of present-day plants to different stresses are discussed based on early, authoritative views of their primary functions during the colonization of land by plants. Flavonols are not as efficient as other secondary metabolites in absorbing wavelengths in the 290-320 nm spectral region, but display the greatest potential to keep stress-induced changes in cellular reactive oxygen species homeostasis under control, and to regulate the development of individual organs and the whole plant. Very low flavonol concentrations, as probably occurred in early terrestrial plants, may fully accomplish these regulatory functions. • Conclusions During the last two decades the routine use of genomic, chromatography/mass spectrometry and fluorescence microimaging techniques has provided new insights into the regulation of flavonol metabolism as well as on the inter- and intracellular distribution of stress-responsive flavonols. These findings offer new evidence on how flavonols may have performed a wide array of functional roles during the colonization of land by plants. In our opinion this ancient flavonoid class is still playing the same old and robust roles in presentday plants.
Flavonoids are among the most investigated phytochemicals due to their pharmacological and therapeutic activities. Their ability to chelate with metal ions has resulted in the emergence of a new ...category of molecules with a broader spectrum of pharmacological activities. However, the biological significance of these flavonoid–metal ion complexes is yet to be completely explored. Moreover, no concerted efforts have been made to elucidate their molecular targets and mechanisms of action. This review attempts to provide a snapshot of the various biological activities reported for flavonoid–metal ion complexes and their potential as therapeutic agents. Understanding the mechanism of action and the influence of structure will provide a strong basis to design novel flavonoid–metal ion complexes of therapeutic significance.
Enzyme promiscuity is evolutionarily advantageous to plants for gaining new enzyme functions when adapting to environmental challenges. However, this promiscuity can negatively affect the expression ...of genes encoding for plant enzymes in microorganisms. Here, we show that refining the promiscuity of flavonoid 3'-hydroxylase (F3'H) and 4'-
-methyltransferase (F4'OMT) improves (2
)-hesperetin production in
. First, we employed inverse molecular docking to screen a highly substrate-specific ThF3'H from
, which could selectively convert 100 mg L
(2
)-naringenin to (2
)-eriodictyol but not (2
)-isosakuranetin, with a cytochrome P450 reductase from
. Second, we employed a directed evolution approach to restrict the promiscuity of MpOMT from
. The strain harboring the MpOMT
mutant presented a remarkably increased preference for (2
)-eriodictyol. Finally, 27.5 mg L
(2
)-hesperetin was produced, while only minor amounts of (2
)-eriodictyol and (2
)-isosakuranetin accumulated as byproducts. This value represents a 14-fold increase in (2
)-hesperetin compared to the parental strain, along with a dramatic reduction in side products. Our work highlights the benefit of alleviating the promiscuity of plant enzymes when engineering production of natural products by microbial cell factories.
The natural flavonoids, especially their glycosides, are the most abundant polyphenols in foods and have diverse bioactivities. The biotransformation of flavonoid aglycones into their glycosides is ...vital in flavonoid biosynthesis. The main biological strategies that have been used to achieve flavonoid glycosylation in the laboratory involve metabolic pathway engineering and microbial biotransformation. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoid glycosides using biotechnology, as well as the impact of glycosylation on flavonoid bioactivity. Uridine diphosphate glycosyltransferases play key roles in decorating flavonoids with sugars. Modern metabolic engineering and proteomic tools have been used in an integrated fashion to generate numerous structurally diverse flavonoid glycosides. In vitro, enzymatic glycosylation tends to preferentially generate flavonoid 3- and 7-O-glucosides; microorganisms typically convert flavonoids into their 7-O-glycosides and will produce 3-O-glycosides if supplied with flavonoid substrates having a hydroxyl group at the C-3 position. In general, O-glycosylation reduces flavonoid bioactivity. However, C-glycosylation can enhance some of the benefits of flavonoids on human health, including their antioxidant and anti-diabetic potential.
In the urinary system, urolithiasis is the third prevalent disorder which causes severe pain in individuals. Urinary stones are composed of calcium oxalate (CaOx) and calcium phosphate in ...approximately 80% of patients. Although various drugs and surgery operations are used to treat the disease, side effects of drugs and the high recurrence after therapy in patients cannot be ignored. Flavonoids are a large group of plant polyphenols with presumed beneficial effects on several common diseases. Whereas, a very few have reached clinical use. The results of recent studies have shown that the plant flavonoids could effectively inhibit the formation of CaOx stones in vitro and in vivo, correlating with their diuretic, antioxidant, anti-inflammatory, antibacterial properties and other protective effects. Thus, the flavonoids or flavonoid-rich plant extracts endowed with anti-urolithiasis activities and probable mechanisms of actions were reviewed. In addition, we also put forward some issues needed to be concerned in future investigations as well as offered prospects and challenges for developing the plant flavonoids into drugs for stone prevention.
Findings from existing prospective observational studies on the protective associations of flavonoid intake and the risk of Alzheimer disease and related dementias (ADRD) are inconsistent largely due ...to limitations of these studies.
To examine the prospective relation between total and 6 classes of dietary flavonoid intake and risk of ADRD and Alzheimer disease (AD) while addressing limitations of earlier observational studies.
We used data from the Framingham Heart Study Offspring Cohort exams 5 through 9. Participants were ADRD-free with a valid FFQ at baseline. Flavonoid intakes were updated at each exam to represent the cumulative average intake across the 5 exams, and were expressed as percentile categories of intake (≤15th, >15th to 30th, >30th to 60th, >60th) to handle their nonlinear relation with ADRD and AD. Cox proportional hazards regression was used to estimate the HRs for the association between the flavonoid intakes and incidence of ADRD and AD.
Over an average follow-up of 19.7 y in 2801 participants (mean baseline age = 59.1 y; 52% females), there were 193 ADRD events of which 158 were AD. After multivariate and dietary adjustments, individuals with the highest (>60th percentile) intakes of flavonols, anthocyanins, and flavonoid polymers had a lower risk of ADRD relative to individuals with the lowest intakes (≤15th percentile), with HRs (95% CI; P-trend) of 0.54 (0.32, 0.90; P = 0.003) for flavonols, 0.24 (0.15, 0.39; P < 0.001) for anthocyanins, and 0.58 (0.35, 0.94; P = 0.03) for flavonoid polymers. The same pattern of associations was seen with AD for flavonols and anthocyanins but not for flavonoid polymers.
Our findings imply that higher long-term dietary intakes of flavonoids are associated with lower risks of ADRD and AD in US adults.
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