Flavonoids: a review of probable mechanisms of action and potential applications

▪ Abstract Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5000 different flavonoids have been described. The six major subclasses of flavonoids include the flavones (e.g., apigenin, luteolin), flavonols (e.g., quercetin, myricetin), flavanones (e.g., naringenin, hesperidin), catechins or flavanols (e.g., epicatechin, gallocatechin), anthocyanidins (e.g., cyanidin, pelargonidin), and isoflavones (e.g., genistein, daidzein). Most of the flavonoids present in plants are attached to sugars (glycosides), although occasionally they are found as aglycones. Interest in the possible health benefits of flavonoids has increased owing to their potent antioxidant and free-radical scavenging activities observed in vitro. There is growing evidence from human feeding studies that the absorption and bioavailability of specific flavonoids is much higher than originally believed. However, epidemiologic studies exploring the role of ...

DIETARY FLAVONOIDS: Bioavailability, Metabolic Effects, and Safety

Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals.

Phenolic secondary metabolites play an important role in plant-derived food quality, as they affect quality characteristics such as appearance, flavour and health-promoting properties. Their content in foods is affected by many factors that influence phenolic stability, biosynthesis and degradation. In terms of their biosynthesis the key enzyme phenylalanine ammonia-lyase (PAL) is especially relevant, as it can be induced by different stress (environmental) conditions. In addition, polyphenol oxidases (PPO) and peroxidases (POD) are the main enzymes responsible for quality loss due to phenolic degradation. The different factors affecting phenolic-related food quality are reviewed. These include internal (genetic) and environmental (agronomic) factors, technological treatments applied during postharvest storage of fruits and vegetables, as well as processing and storage of the processed products. The different strategies that are required to either maintain or enhance the phenolic-related quality of foods are critically reviewed. Genetic modification designed to decrease polyphenol oxidases or peroxidases is not always a feasible method, owing to side problems related to the growth and defence of the plant. Agronomic treatments can be used to enhance the phenolic content and pigmentation of fruits and vegetables, although the information available on this topic is very scarce and even contradictory. Some postharvest treatments (cold storage, controlled or modified atmospheres, etc) can also improve phenolic-related quality, as well as new processing methods such as irradiation (gamma, UV), high-field electric pulses, high hydrostatic pressures and microwaves. Les composes phenoliques, metabolites secondaires des plantes, jouent un role dans la qualite des fruits, au niveau de l'apparence, de la flaveur et des qualites nutritives. L'enzyme cle de leur biosynthese est la phenylalanine ammonium-lyase, regulee par les facteurs environnementaux. La polyphenol oxydase et la peroxydase sont responsables des degradations donc des pertes de qualite. Les differents facteurs internes (genetiques) et externes (agronomiques) affectant la qualite des produits vegetaux sont etudies. Les differentes mesures envisageables (modification genetique, traitements chimiques ou physiques apres recolte) pour modifier le contenu en compose phenoliques et donc la qualite des produits vegetaux sont etudies.

Phenolic compounds and related enzymes as determinants of quality in fruits and vegetables

Health-Promoting Components of Fruits and Vegetables in the Diet

The intake of flavonols, flavones and isoflavones by Japanese women was calculated from our food-phytochemical composition table. The relationship between intake of these phytochemicals and various anthropometric and blood chemistry data was analyzed in a cross-sectional study. The subjects were 115 women volunteers, aged 29-78 y, living in the northern part of Japan. Each subject completed a 3-d dietary record and received a health check up, including urine and blood sampling for biochemical analysis. Total mean intakes of flavonoids (sum of flavonols and flavones) and isoflavones were 16.7 and 47.2 mg/d, respectively. The major source of flavonoids was onions (45.9%) and that of isoflavones was tofu (37.0%). Total intake of isoflavones exceeded that of other dietary antioxidants, such as flavonoids, carotenoids (3.5 mg/d) and vitamin E (8.2 mg/d), and was approximately one half of the vitamin C intake (109 mg/d). The total intake of flavonoids was inversely correlated with the plasma total cholesterol concentration (TC) (r = -0.236, P: < 0.05) and plasma LDL cholesterol concentration (LDL-C) (r = -0.220, P: < 0.05), after the adjustment for age, body mass index and total energy intake. As a single component, quercetin was inversely correlated with both TC (r = -0.261, P: < 0.01) and LDL-C (r = -0. 263, P: < 0.01). Among Japanese, flavonoid and isoflavone intake is the main component among nonnutrient phytochemicals with antioxidant potential in the diet. These results suggest that a high consumption of both flavonoids and isoflavones by Japanese women may contribute to their low incidence of coronary heart disease compared with women in other countries.

Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration.

The protective effect of alpha G-Rutin against ferric nitrilotriacetate (Fe-NTA)-induced renal damage was studied in male ICR mice. Fe-NTA induces renal lipid peroxidation, leading to a high incidence of renal cell carcinoma in rodents. Administration of alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation 30 min after i.p. injection of Fe-NTA (7 mg Fe/kg) most effectively suppressed renal lipid peroxidation. Repeated i.p. injection of Fe-NTA (2 mg Fe/kg/day for the first 3 days and 3 mg Fe /kg/day for 12 days, 5 days a week) causes subacute nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal tubules. A protective effect was observed in mice given alpha G-Rutin 30 min after each Fe-NTA treatment. To elucidate the mechanism of protection by alpha G-Rutin, the pharmacokinetics and hydroxyl radical-scavenging effect of alpha G-Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), respectively. When mice were given alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of alpha G-Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min, alpha G-Rutin inhibited the formation of DMPO-OH in a concentration-dependent manner. Further, chelating activity of alpha G-Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed alpha G-Rutin works as an antioxidant in vivo either by scavenging reactive oxygen species or by chelating ferric ions and this serves to prevent oxidative renal damage in mice treated with Fe-NTA.

Protection by αG-Rutin, a Water-soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

Given n points inside a unit square (circle), let d n (c n ) denote the maximum value of the minimum distance between any two of the n points. The problem of determining d n (c n ) and identifying the configuration of that yields d n (c n ) has been investigated using geometric methods and computer-aided methods in a number of papers. We investigate the problem using a computer-aided search and arrive at some approximations which improve on earlier results for n=59, 73 and 108 for the unit square, and also for n=70, 73, 75 and 77, ⋯ , 80 for the unit circle. The associated configurations are identified for all the above-mentioned improved results.

Maximin Distance for n Points in a Unit Square or a Unit Circle

To evaluate the in vivo antioxidant activity of flavonoids, the time course of the blood plasma level and protective effect against oxidative stress were examined in ICR male mice exposed to γ-rays or ferric nitrilotriacetate (Fe-NTA). Fe-NTA induces renal lipid peroxidation leading to a high incidence of renal cell carcinoma in rodents. We used the flavonoid αG-Rutin, which has been used as a food additive for coloring. Its main component is 4G-α-D-glucopyranosyl-rutin. αG-Rutin is water-soluble. High-performance liquid chromatography (HPLC) analysis showed that αG-Rutin was rapidly absorbed into the circulation. The αG-Rutin concentration reached its highest level 30 min after gastric intubation (50 μmol rutin/kg) and then decreased within 60 min. When mice received αG-Rutin (50 μmol rutin/kg) by single gastric intubation 30 min before γ-irradiation (1.5 Gy), a significant reduction in the frequency of micronucleated reticulocytes (MNRETs) was observed. A single gastric intubation of αG-Rutin (50 μmol rutin/kg) 30 min after intraperitoneal injection of Fe-NTA (7 mg Fe/kg) suppressed renal lipid peroxidation. Furthermore, αG-Rutin given in drinking water ad libitum (3.3 mmol rutin/L) showed a protective effect against subacute nephrotoxicity induced by repeated intraperitoneal injection of Fe-NTA (3–4 mg Fe/kg/day) with increased survival. These results suggest that absorbed αG-Rutin works as an antioxidant in vivo by either scavenging reactive oxygen free radicals or forming a chelating complex with transition metal cations.

Protective Effect of αG-Rutin on Oxidative Stress in Mice

Given n points inside a unit square (circle), let d n (c n ) denote the maximum value of the minimum distance between any two of the n points. The problem of determining d n (c n ) and identifying the configuration of that yields d n (c n ) has been investigated using geometric methods and computer-aided methods in a number of papers. We investigate the problem using a computer-aided search and arrive at some approximations which improve on earlier results for n = 59, 73 and 108 for the unit square, and also for n = 70, 73, 75 and 77,...,80 for the unit circle. The associated configurations are identified for all the above-mentioned improved results.

Rika Mochizuki

Papers

Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration.

Protection by αG-Rutin, a Water-soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

Maximin Distance for n Points in a Unit Square or a Unit Circle

Protective Effect of αG-Rutin on Oxidative Stress in Mice

Maximin distance for n points in a unit square or a unit circle