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polish journal of food and nutrition sciences www.pan.olsztyn.pl/journal/ e-mail: joan@pan.olsztyn.pl Pol. J.

Food Nutr. Sci. 2008, Vol. 58, No. 4, pp. 407-413

QUERCETIN AND ITS DERIVATIVES: CHEMICAL STRUCTURE AND BIOACTIVITY – A REVIEW Małgorzata Materska
Research Group of Phytochemistry, Department of Chemistry, Agricultural University, Lublin
Key words: quercetin, phenolic compounds, bioactivity Quercetin is one of the major dietary flavonoids belonging to a group of flavonols. It occurs mainly as glycosides, but other derivatives of quercetin have been identified as well. Attached substituents change the biochemical activity and bioavailability of molecules when compared to the aglycone. This paper reviews some of recent advances in quercetin derivatives according to physical, chemical and biological properties as well as their content in some plant derived food.

INTRODUCTION In recent years, nutritionists have shown an increased interest in plant antioxidants which could be used in unmodified form as natural food preservatives to  replace synthetic substances [Kaur & Kapoor, 2001]. Plant extracts contain various antioxidant compounds which occur in many forms, thus offering an  attractive alternative to  chemical preservatives. A small intake of these compounds and their structural diversity minimize the  risk of  food allergies. Additionally, the substances isolated from edible plants are the least toxic to  a  human body. For this reason, the  naturally occurring bioactive compounds, that may act in  synergy with drugs in pharmacological applications, can be adapted in “combination therapy”, thus enabling the use drugs at lower concentration but with an  increased efficiency [Russo, 2007]. This strategy can play a major role in the future of cancer prevention [Reddy et al., 2003]. This aspect of research is presently at the developmental phase, but the search for new substances occurring naturally in plants to be used as food preservatives or as a new therapeutic agents shifts the scientists’ focus to, among others, phenolic compounds [Singh, 2002]. Quercetin, a flavonol occurring in fruit and vegetables is a  food component with proven beneficial impact on health [Kaur & Kapoor, 2001]. Its biochemical activity is well documented. It is one of the most potent antioxidants among polyphenols [Formica & Regelson, 1995; Prior, 2003; Rice-Evans et al., 1997]. Quercetin has also been demonstrated to display the  antiviral, antibacterial, anticarcinogenic and antiinflammatory effects [Di Carlo et al., 1999; Formica & Regelson, 1995; Harborne & Williams, 2000]. The  anticarcinogenic properties of  quercetin result from its significant impact on an  increase in  the  apoptosis of  mutated cells, inhibition

of  DNA synthesis, inhibition of  cancerous cell growth, decrease and modification of cellular signal transduction pathways [Erkoc et al., 2003]. In food, quercetin occurs mainly in a bounded form, with sugars, phenolic acids, alcohols etc. After ingestion, derivatives of quercetin are hydrolyzed mostly in the gastrointestinal tract and then absorbed and metabolised [Scalbert & Williamson, 2000; Walle, 2004; Wiczkowski & Piskuła, 2004]. Therefore, the content and form of all quercetin derivatives in  food is significant for their bioavailability as aglycone. Progress in  highly sensitive and high-precision testing equipment made scientists able to isolate and identify compounds which sometimes occur in marginal quantities and are characterised by a highly complex structure. The  number of  new natural plant substances described in literature, including quercetin derivatives, is still increasing. This progress is illustrated by the fact that in the flavonol group, more than 230 new compounds were identified in  the  years 1986-1992  [Harborne 1994], while 180  new structures were isolated in the  years 2001-2003 [Williams & Grayer, 2004]. Research into the  biological properties of  the  flavonoid derivatives has become popular as well. The  list of  investigated substances includes compounds with antioxidant properties as a  potential source of  food preservatives [Smith-Palmer et  al., 2001; Vurma et al., 2006], compounds with antibacterial and antiviral properties as an  alternative to  antibiotics [Chun et al., 2005; Shetty, 2004] as well as substances with allelopathic properties which could replace pesticides and insecticides [Simmonds, 2001; Souto et al., 2000]. This paper focuses on quercetin derivatives most frequently occurring in the  nature to determine the impact of their chemical structure on the physical properties and biological activity.

Author’s address for correspondence: Małgorzata Materska, Agricultural University, Department of Chemistry, Research Group of Phytochemistry, ul. Akademicka 15, 20-950 Lublin, Poland; tel. (48 81) 445 67 49; fax: (48 81) 533 35 49; e-mail: malgorzata.materska@up.lublin.pl © Copyright by Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences

but these compounds occur relatively rarely in nature. 1994.. C-glycosides are another type of quercetin derivatives.. 2005a] and buckwheat [Kalinova et al.. Quercetin 3-O-glycosides occur as monosaccharides with glucose. Oomah & Mazza. 2004]. 2004]. among others. [2004] Slimestad et al. Contents of some quercetin derivatives in plant derived products. 1996].m. [2005] Berardini et al. [2003] Quercetin 3-O-rutinoside (rutin) 35-98 x 103 442-511 10-50 Quercetin 3-O-6’’-acetylglucoside Quercetin 3-methyl ether Quercetin 3. [2005] Chang & Wong [2004] Chang & Wong [2004] Quercetin 3-O-galactoside Quercetin 3-O-glucoside Quercetin 3-O-xyloside Quercetin 3-O-rhamnoside 77-1045 100-690 12-22 9-37 10-278 0-116 113-993 55 109 81-1065 Quercetin 3-O-glucuronide Quercetin 7-O-glucoside Quercetin 3-O-diglucoside Quercetin 3.4’-diglucoside Quercetin 3-O-rhamnoside-7-O-glucoside 0-730 20-120 120-640 169-1372 Nemeth & Piskuła [2007] Materska & Perucka [2005] Kim et al. 2005].. an example of such derivative is rutin: 3-O-rhamnosylglucoside (4). is an example of this derivative. 1999] and peppers [Materska et al.. Glycosides Quercetin O-glycosides are quercetin derivatives with at least one O-glycosidic bond which are widely distributed in  the  plant kingdom. like onion. Quercetin 3-O-glucoside (2) was found. More than half of  flavonol structures identified in  the  past decade are compounds containing alkyl substituents in their molecules [Williams & Grayer. in  beans [Chang & Wong. [2006] Oomah & Mazza [1996] Slimestad et al. Another glycosylation site which occurs in quercetin derivatives is hydroxyl group at C-7  carbon. In  addition to  monosaccharides and disaccharides. 3-O-rhamnoside-7-O-glucoside (6) is such a  compound found in peppers [Materska et al. Yet.1 Content (mg/kg) d. olive oil [Ryan et al. 1994. [2003] Zeng & Wang [2003] Zeng & Wang [2003] Zeng & Wang [2003] Zeng & Wang [2003] Berardini et al. 2004]. Quercetin bounded to disaccharides is also frequently detected in plants. The most References Berardini et al. The  most common quercetin glycosylation site is the  hydroxyl group at C-3  carbon.3’-dimethyl ether . 2004]. and some. the number of compound is labeled in parenthesis. Practically every plant contains compounds of  this group. Quercetin derivatives Source Mango – fruits Plums Blueberry Cranberry Chokeberry Lingonberry Mango-fruits Beans Plums Onions Mango – fruits Mango – fruits Pepper – fruits Cranberry Lingonberry Lettuce Chicory Beans Beans Onions Pepper – fruits Plums Cherries Tomatoes Buckwheat – leaves Buckwheat – seeds Chokeberry Beans Honey Honey 130-365 28-77 18-137 3. rhamnose or xylose. gaTable 1. Quercetin 7-O-glucoside (5) which is found e. [2004] Innocenti et al. 2006. [2005b] Kalinova et al. 2004]. glycosylation at C-7 is more frequently accompanied by C-3 substitution of –OH group.m. Materska lactose. [2005a] Chang & Wong [2004] Yao et al. The content of few common quercetin derivatives in some fruits and vegetables is shown in Table 1. contains five hydroxyl groups whose presence determines the  compound’s biological activity and the  possible number of  derivatives.g.408 CHEMISTRY OF QUERCETIN DERIVATIVES Structure A  molecule of  quercetin (1) (Figure 1)..3 0. sugar chains with three-. in  sage [Lu & Foo. 2000].. 2004]. 76-1470 f. [2005] Kim et al. [2005] Materska & Perucka [2005] Zeng & Wang [2003] Zeng & Wang [2003] Nicolle et al.2 10-49 x 103 710 2-3. [2003] Nemeth & Piskuła [2007] Berardini et al. whereas quercetin 3-O-rhamnoside (3) was detected in spinach [Kuti & Konuru. 1998]. while their chemical structure is shown in  Figure 1. spinach [Kuti & Konuru. four. chokeberries [Slimestad et al. Williams & Grayer. 2003]. [2003] Goncalves et al. Significant quantities of this compound are found in tea [Erlund.and five saccharide moieties have also been identified in quercetin 3-O-glycoside derivatives [Harborne. The  main groups of  quercetin derivatives are glycosides and ethers as well as the less frequently occurring sulfate and prenyl substituents [Harborne.2-9. [2003] Yao et al.3-2. Williams & Grayer. The main groups of quercetin derivatives are characterized below. 2003]. contain vast quantities of  these substances in  highly diversified forms [Fossen et al. 2002] and mango fruit [Berardini et al. [2005] Chang & Wong [2004] Kim et al. These compounds are found in various fruits and vegetables (Table 1) and other anatomical parts of plants [Wiczkowski & Piskuła. ~ 35 146 97 415 118 M. 2004].

2001]. Rha: rhamnose. Quercetin 7. Quercetin 3-O-rhamnoside-7-O-glucoside (7). 6. Z: prenyl. 3. The compounds identified in the recent years include 3-sulfate-7-O-arabinoside (9). Quercetin 3-O-rhamnoside (quercitrin) (4). Quercetin 6-C. caffeic and ferulic acid [Harborne. Quercetin 3-(2’’-acetylgalactoside) (8). Ether derivatives of  quercetin which also contain sugar substituents are frequently found in  nature.  FIGURE 1. 2004]. Quercetin 5-methyl ether (azaleatin) (12). is an example of an acyl derivative of quercetin which was identified in the last decade [Jürgenliemk & Nahrstedt. they were: quercetin 7-methoxy-3-glucoside (15) and quercetin 3’-methoxy-3­ ‑galactoside (16) [Lu & Foo. John’s wort. 1994]. Wide distribution of quercetin ethers is indicated by the fact that nearly every monoether derivative has a common name (Figure 1. Sulfate derivatives of quercetin occur relatively rarely in nature.glucoside (6). 4’-pentahydroxyflavon (quercetin) (2). mostly methanol [Harborne. e.methyl ether (isohramnetin) (14). 2002]. gallic. 2002]. Quercetin and its derivatives. 3’.. . X: rhamnosylglucose. 1994].glucoside (8). 3’.5’-di-C-prenyl quercetin (17) found in paper mulberry [Son et al. found in the cornflower [Flamini et al.methoxy -3-O-galactoside (17).5’-Di-C-prenylquercetin Substituents R1 OH O-Glc O-Rha O-X OH O-Rha OH O-Y O-Sul O-Glc OH OH OH OH O-Glc O-Gal OH R2 OH OH OH OH OH OH OH OH OH OH O-M OH OH OH OH OH OH R3 H H H H H H Glc H H H H H H H H H Z R4 OH OH OH OH O-Glc O-Glc OH OH O-Ara OH OH O-M OH OH O-M OH OH R5 OH OH OH OH OH OH OH OH OH O-Sul OH OH O-M OH OH O-M OH R6 OH OH OH OH OH OH OH OH OH OH OH OH OH O-M OH OH OH R7 H H H H H H H H H H H H H H H H Z Glc: glucose. Quercetin 3-O-glucoside (izoquercetin) (3). 2001]. malonic and 2-hydroxypropionic acid.Quercetin 3-O-rhamnozyl-(1→6)-glucoside (rutin) (5). In addition there are also derivatives containing alkyl substituents. Quercetin 4’. The  number of  naturally occurring quercetin glycosides may be higher due to the fact that sugar moiety can additionally contain acyl and sulfate substituents [Williams & Grayer. Quercetin may contain up to five ether groups in various configurations. 2004] and quercetin 3-O-glucoside3’-sulfate (10). Sul: -SO3Na. The most common hydrocarbon forming such derivatives is prenyl (3-methylbut-2-en). Quercetin 3-(2’’-acetylgalactoside) (9). Such compounds were identified in sage. Quercetin 3-O-glucoside-3’-sulfate (11). compounds 11-14) [Harborne. 7.g. frequent site of C-glycosylation is the C-6 carbon. in 3. Ethers Ether bonds may be formed between every hydroxyl group of a quercetin molecule and an alcohol molecule. found in  saltbush [Williams & Grayer. Y: 2-acetylgalactose. or aromatic acids.methyl ether (tamarixetin) (15). 1994]. 4’-pentahydroxy-6-glucose flavon (7) which was first identified in Ageratina calophylla [Harborne. Quercetin 7-methoxy-3-O-glucoside (16). 1994]. found in St. Quercetin 7-O.. such as acetic. 5. including benzoic.Quercetin and its derivatives – a review 409 Systematic name (common name) (1). Acyl derivatives include links with aliphatic acids. Quercetin 3’. 7. Quercetin 3’.methyl ether (rhamnetin) (13). Ara: arabinose. 4. M: –CH3. Quercetin 3-sulfate-7-O-arabinoside (10). The  lipophilic derivative of  quercetin identified in  the  past decade is 6.

Materska & Perucka.. 2005]. but generally recognized antioxidants. Matetrska & Perucka.. the highest reduction potential is demonstrated by the 4’-OH group in B-ring. such as vitamin C and quercetin. Burda & Oleszek 2001. 1998. Flavonoids. 2005. In  view of  the  number of  factors which determine the chemical properties of quercetin derivatives. In  the  case of  quercetin derivatives. The lower antioxidant activity of  quercetin derivatives is mainly due to  the  blocking of  hydroxyl groups by sugar or alkoxyl substituents. which are cytosol-soluble. it has been shown that the antioxidant activity of a compound is determined by the presence of free hydroxyl groups and their mutual location [Rice-Evans et al. analyses carried out in various model systems have led to the determination of  functional groups in  flavonoid molecules M. 2003]. 2001. 1997. There are many methods for determining antioxidant activity. only isolated derivatives of both quercetin and other flavonoids have been investigated. 2003]. These compounds are particularly widespread in the families Labiatae or Compositae. This change in character from lipophilic to hydrophilic is very significant to plants for glycosidic derivatives of quercetin.. are lipophilic. concluded that in reference to superoxide radicals. Glycosylation of at least one hydroxyl group of quercetin derivatives results in  an  increase of  its hydrophilicity. Materska FIGURE 2. the quercetin molecule has a lipophilic character.. determination of antiradical activity in relation to  peroxide radical. In  reaction with DPPH. Goupy et al. in  comparison to  quercetin. 2005]. the  increased hydrophilicity of  quercetin glycosides modifies the coefficients of distribution between the aqueous and lipid phase. ABSORPTION AND METABOLISM OF QUERCETIN DERIVATIVES Absorption and metabolism of quercetin and its derivatives has attracted much attention in relation to their pro-healthy . [2006]. The most popular tests are: determination of antiradical activity in reaction with DPPH synthetic radical (1.. 2006]. Chemical properties The  most extensively investigated chemical property of  phenolic compounds is their antioxidant activity. 1997]. C-methyl and prenyl derivatives of  flavonoids. its high antiradical activity has been shown to be determined by the presence of 1. Indirect method to determine antioxidant activity is metal ions chelation power. Rice-Evans et al. Even though the presence of a hydroxyl group at the C-3 carbon of quercetin enables the regeneration of the catechol ion through the addition of the proton from the solution [Goupy et al. Williams & Grayer. which is of great significance in lipid systems such as TEAC or β-carotene emulsion [Burda & Oleszek. and most of them involve the description of antioxidant relative ability to  scavenge free radicals in  comparison with a known antioxidant [Rice-Evans et al. which are able to  chelate Fe2+ or Cu2+ ions render them inactive to  participate in  free radical reactions [Morel et al. a research investigating the  scavenging activity of  quercetin derivatives in relation to  radicals does not fully support the theory that 4’-OH in  B ring is mainly responsible for high scavenging power. quercetin derivatives were also demonstrated to  display a  lower activity in  comparison with free aglycone [Cos et al. They can be easily isolated from hydrophilic compounds by immersing plant tissue in  acetone [Williams & Grayer.410 Physical properties Despite the presence of five hydroxyl groups. determination of  antioxidant activity of  compounds in  relation to radicals generated in  the lipid phase. 2006]. antioxidant activity is often accompanied by antiviral and antibacterial activity of these compounds [Chun et al. It was supported by a  research comparing the  antiradical activity of  quercetin and its C(3)-OH and C(4’)-OH glycoside derivatives. while C(3)-OH derivatives of quercetin showed reducing potential comparable with that of free aglycone [Burda & Oleszek. 1997]. In  addition. To date. morin. myricetin and quercetin. e. Wang et al. 2003]. 1995. 2004]. 1993]. Results obtained so  far have enabled determining general relationships. On the other hand. responsible for the  activity in  the  investigated system [Wang et al.2 dihydroxybenzene (catechol) in the B ring [Burda & Oleszek.. In other model systems. 2001. scavenging activity in  a  xanthine/xanthine oxidase system despite a free 4’-OH group in B-ring [Materska et al. kaempferol. 1995]. as well as with chelation of metal ions and inhibition of the activity of oxidases [Bartosz.. Quercetin 3-O-glycoside derivatives such as rutin and quercitrin are characterised by much lower. 2003]. Antioxidants are capable of  neutralizing free radicals which are always present in  food as well as in  cells of  a  human body [Bartosz. Research investigating relationships between the  structure and antioxidant activity of phenolic compounds has been conducted for many years. Additionally.. i. Regarding quercetin reaction with DPPH radical.e..and hydrophilic. Quercetin derivatives can be both lipo. investigating the  antioxidant activity of flavonoid aglycones. including fisetin. quercetin donates two hydrogen atoms and is transformed into a  quinone intermediate (Figure 2). in press]. are also used to this end.. The antioxidant properties of phenolic compounds are linked with their ability to transfer a hydrogen or an electron. etc.g. 2004].. 2003]. glycosilation at C(4’)-OH markedly decreased the H-donating ability [Goupy et al. Wang et al.. β-carotene emulsion system or TEAC (Trolox Equivalent Antioxidant Capacity). can be easier transported to various parts of the plant and stored in vacuoles [Rice-Evans et al.. Trolox is a synthetic antioxidant frequently applied as a reference compound. but the availability of relevant information has been on the rise in the recent years. OH· hydroxyl radical. In general. In addition.1-diphenylpicrylhydrazyl radical). 1997.. flowers or fruits. depending on the type of substituents in the molecule. O-methyl.. including quercetin derivatives. Pathway of oxidative changes in quercetin reaction with DPPH radical in protic solvents [Goupy et al. empirical research is needed to  confirm or exclude the  specific activity. Rotelli et al. 2001]. They are synthesized by glands located on the surface of leaves.

2000]. When administered to rats.. The  anticarcinogenic activity of  tetrasaccharide derivative of quercetin: quercetin 3-O-rhamnosyl (1→6) –O[glucosyl (1→3) rhamnosyl (1→2) – O-glactoside was also demonstrated by Vilegas et al. because in this form quercetin predominates in diet.. After absorption. On the  other hand. 1999]. Simple derivatives such as quercetin mono-glycosides: 3-O-glucoside and 3-O-rhamnoside as well as diglycoside – rutin... Miyazawa et al. quercetin 3-O-rhamnoside minimized damage to the colon. 2004]. A lipophilic quercetin molecule can be easily absorbed by the stomach and then secreted in the bile [Crespy et al. BIOACTIVITY Research into the  bioactivity of  quercetin derivatives and its impact on human health is still at the developmental . 2002].5. 2003. additionally absorption of quercetin glycosides depends on the position and nature of sugar substitutions [Cermak et al. 2003]. have been best investigated to  date. Two other quercetin derivatives – quercetin 3-O-xylose (1→2)–rhamnoside and 3-O-rhamnoside – decreased the  swelling caused by chemically-induced inflammation in mice [Harborne & Williams. 2000]. Scalbert et al. glycosides are hydrolysed by β-glycosidases present in cytosole of small intestine mucosa cells [Day et al. 2006]. 1999].... quercetin is metabolised in analogy with drugs and other extrinsic compounds [Scalbert & Williamson. Rotelli et al. Scalbert & Williamson. 1994]. A  human body needs these substances to absorb and use vitamin C. In addition.. rutin has also been found to display chemopreventive properties. On this basis it has been suggested that cellular effects of flavonoids may be mediated by their interactions with intracellular signalling cascades [Williams et al. For this reason absorption of those compounds is delayed. It has been clearly shown that quercetin aglycone and glycosides are absorbed from the gastrointestinal tract to a different extent.. [1999]. represent a considerable part of these food constituents.. The second mechanism enabling intestinal absorption of  quercetin glycosides assumes the possibility of interacting with sodium-dependent glucose transporter SGLT1 [Wolfram et al. Yet it  is likely that lipophilic ethers of  quercetin are absorbed in analogy to quercetin aglycone.. Williams et al. The successive stages of quercetin metabolism include enzymatically controlled reconjugation reactions.. 2002].3’-trihydroxy-7. 2000]. Similar properties were observed in  methoxyl derivatives of  quercetin: 3.7. 2000]. There are two mechanism enabling intestinal absorption of  quercetin glycosides. 1998].. Quercetin glycosides are not affected by pH conditions of the stomach and pass through the small intestine where they are partially deglycosylated and absorbed [Gee et al. as for many flavonoids. It is common knowledge that metabolic modification of  quercetin derivatives alters their antioxidant properties. are not hydrolyzed by endogenous human enzymes and pass through the small intestine and enter the cecum and colon. 1998]. acting as an agent blocking carcinogenesis induced by heterocyclic amines [Hirose et al.. but the  exact mechanism of  their action is still unresolved. while hydrophilic derivatives with acyl or sulphate substituents must be deconjugated before absorption. After hydrolysis and absorption. and preferred the sugar group at the 3-position [Day et al.. 1993]. 2000].4’-dimethoxyquercetin and 3.4’-dihydroxy-3. sulfated and methylated forms [Day et al. Information on the absorption and metabolism of other than glycosidic derivatives of  quercetin in  a  human body is sparse. 2004]. When investigating the  less known methoxyl derivatives of  quercetin. Quercetin derivatives. 2006. In  the  first. as: glucuronidation.3’-trimetoxyflavon) showed the  antimutagenic activity towards chemically-induced mutagens (umu test). rutin protects liver cells [Janbaz et al. prevented diarrhea and stabilized the  transport of  fluids in  the  colon of rats [DiCarlo et al. quercetin 3-O-rhamnoglucoside and quercetin-3-O-rhamnoside. Investigators have also found that quercetin 3-O-glucoside and rutin contribute to the relaxation of smooth muscles in mammals.4’-dimetoxyflavon) and pachypodol (5. The total flavonoid intake from dietary sources is estimated to be from several hundred miligrams to 1 gram per day [Formica & Regelson. investigations of  protective mechanism of  quercetin and its derivatives on oxidative damages of  in vitro rat C6 glioma cells showed that quercetin but neither rutin and quercitrin [Chen et al.7-dimethoxyquercetin [Harborne & Williams. 2000]. nor 3-O-glucoside and 3-O-acetylglucoside [Zielińska et al.. Hertog et al. Investigations on the  bioavailability and metabolism of quercetin derivatives focused mostly on glycosides.. 2000]. CONCLUSIONS It is common knowledge that flavonoid antioxidants are related to various beneficial effects exerted on human health. The  in vivo investigations of the beneficial and/or toxic action of flavonoids tend toward a theory that products of fla- value. 2004]. e.. where they are hydrolyzed by colon microflora to quercetin and sugar [Scalbert & Williamson. 1995... 2003] were active as cells protectors.Quercetin and its derivatives – a review 411 stage.g. 2002] and suppresses hemoglobin oxidation [Grinberg et al. metabolism of quercetin derivatives in the enterocyte is the rate-limiting step of their bioactivity. 1998. Rutin has also anti-inflammatory properties which are displayed mostly in  respect of  chronic diseases [Obied et al. This β-glycosidase had a high affinity particularly towards flavonol glucosides.. Glycosides of quercetin with a substituent other than glucose. Yet. Graf et al. [2000] concluded that obuine (3. It has been shown that LPH-mediated hydrolysis was the main absorption pathway of quercetin–3-glucoside. 2002. Due to  its antioxidant activity. 2005. 1998. in  vivo concentrations of  flavonoids and their metabolites are lower than those of  antioxidant nutrients such as ascorbic acid and α-tocopherol [Williams et al. glycosides in particular. It is common knowledge that having been ingested both quercetin as quercetin derivatives undergo many metabolic conversions and appear in body tissues almost as glucuronated. they are a  potential substrate for lactose phlorizin hydrolaze (LPH) in the brush border membrane [Day et al.. sulfation or hydroxylation [Scalbert & Williamson. Ample investigations have confirmed a beneficial effect of quercetin derivatives. methylation. In  addition. 2000].

Agric... Proc. Crespy V. Takahashi S. Ameho C. Moutinho­ ‑Pereira J. 2000. Futakuchi M. 37..... Pieters L.Y.Y. Landbo A. 2004]. Kromhout D.. Ieri F. 19... Poel B. 1998. Kosonen T. 179–203 (in Polish). Williams Ch. Berardini N. J.. Erkoc S.. DuPont M..B. 2004.. Gee J. Kim Y. Advances in flavonoid research since 1992. Vrchotova N. Fossen T.. Biochem. Agric. Screening of mango (Mangifera indica L. J... Gilani A. Food Chem.J.. Andersen O. Lin Ch..S. 1994.Y. J. 985–992. while considering quercetin derivatives as food protectors.R. Agric.. 133. Berghe D. Graf B. 6. Knudsen D..J. Nutr..A.... Perttunen K.. Phenolics: blocking agents for heterocyclic amine-induced carcinogenesis. Ogawa K. Mascolo N. 1995. Goupy P. J.. . 618–621.... Harborne J. Biochem..C. Food Chem. 615–622. Estimation of daily intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Day A. Mclauchlan R. 2802–2807. Flavonoids: old and new aspects of a class of natural therapeutic drugs. 631..J. 1993.B.. 2005. 50. DuPont M. 2005. PWN. 557–563. Food Chem. Saeed S. 643–649... Mol. Erlund I. 481–504. 12. 22.W... 2. 33.. Antioxidant capacity and phenolic content in leaf extracts of tree spinach (Cnidoscolus spp. 1998. Morgan M.S.. M. Flavonoids from red onion (Allium cepa). Chun O...P. Food Chem. Chen Ch. epicatechin and rutin in  common buckwheat plants (Fagopyrum esculentum Moech). Dufour C.A.B... Food Chem. 559–564.. Johnson I..). Beifuss U. Antioxidant activity of the main phenolic compounds isolated from hot pepper fruit (Capsicum annuum L..B. Polyphenolics of Salvia – a review.. Kenraali J. 33.Y. 27. 11. Planta Medica.A.. Lu Y.H. Review of the biology of quercetin and related bioflavonoids.. Cermak R. 8. J.). Demigne C. Mulinacci N.. Pharmacol. 73. J.A. Morelli I.. Silva A. Oleszek W. 141–146. 2002. Janbaz K. Food Chem. 15. Rhodes M.. 9. Kuti J.A. Plumb G...J. Phytochemistry. Hirose M... Shirai T. 71–76.. 337–353. Two flavonoids and other compounds from the  aerial parts of  Centaurea brakteata from Italy. Toxicol.. Technol..O. 5330–5335.. 40. Antioxidants in  fruits and vegetables – the  millennium’s health. 51..A.. Fitoterapia.R. Katan M.E. 55. Schieber A. Cos P. 2000. Williamson G.... The Flavonoids. Quercetin. Diaz J.Y. 68. Food Chem. Effect of ripeness and postharvest storage on the  phenolic profiles of  cherries (Prunus avium L.. Regelson W. Rachmilewitz E.. 1994.A..S.. 281–285. 1061–1080. Rad... ed.412 vonoid metabolism may modulate lipid and protein kinases. 53.. 6694–6699. 49. 2001.. 19–25... 436. 17. Antognoli E.. Izzo A. Rhodes M. Conrad J.. 54. Vincieri F. 56. Pharmacol. Goncalves B. Nutr. Food Chem. Williamson G.. Int... pp. Di Carlo G. Morgan M.. 2001.. Besson C. FEBS Lett. 18. 468.. 1999.S. Gallori S. Faulds C. 29. Ying L.. Distribution of vitamin E. 2002.G. Capasso F.. 523–530. Chen T.. Agric. 2002. 1563–1570. 53. Formica J. Fezer R. Wong Y.. 703–725. J.. 166–170.T.W. Protective effect of rutin on paracetamol.. 2003. Agric. 35.J....G. 1999. FEBS Lett.. J... 53. 2005.Y. 31. 2002.C.. 20. 7. 52.A. 1998. Konuru H. Food Chem. Phytochemistry. 14. 36... Aro A. pp. 117–121.N. Calomme M. 71–75. 2000. Foo L.. 30. 2004. Clin.. 21–29. Wolffram S. 2003. Chapman & Hall. Druga twarz tlenu (The  Second Face of  Oxygen). 34. 545–553. Warszawa.. 39–44. anthocyanins and pectin.. 1995.. Ridley S. 10. Food Chem..... Food Sci. 52. J. Agric. Nat. Quantification of polyphenolics and their antioxidant capacity in fresh plums.. Theoretical investigation of quercetin and its radical isomers.. 3. Free. Materska 16. 6497–6502.J. Agric. Chun S. Protective effects of rutin against hemoglobin oxidation. Agric... 6509–6515. Phytochemistry. J. 2001.. J. Kapoor H... Rosa E.... Morand C. Vattem D. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase.F.. 25..C. Rat gastrointestinal tissues metabolize quercetin.. 117–140.. Carle R. Phenolic compounds from Hypericum perforatum. Maenpaa J.. Identification of flavonoids in Hakmeitau beans (Vigna sinensis) by high performance liquid chromatography-electrospray mass spectrometry (LC-ESI/MS). 4.. Structure-activity realtionship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers... Toxicology. Moon H. Evaluation of  the  phenolic content in  the  aerial parts of different varieties of Cichorium intybus L. Chen Y... Landgraf S. 1750–1756. Flamini G. Kaur Ch. Canada F. Tox. Grinberg L.. Eur. Lee Ch..S.. 21... 52. J. the  antioxidant and antimicrobial activity of unchanged compounds must be confirmed.... 113–126. Agric. Newmark H. Pedersen A. Quercetin inhibition of ROS. 57.J. Kroon P. 48. Phenolic antioxidants from clonal oregano (Origanum vulgare) with antimicrobial activity against Helicobacter pylori. Biol. 2003... Perucka I. Med. Remesy C. Nutr. Agric. Materska M. Hu J. Milbury P.. Jürgenliemk G. Cimanga K. Keskin N... Rhodes M.B..Ch. Deglycosylation of  flavonoid and isoflavonoid glycosides by human small intestine and liver β-glucosidase activity. Vlietinck A. 1998. Burda S. J. squalene. Nahrstedt A. Agric.F. 65. Food Chem.. J. 23. 20. J. Hertog M. acting as signalling molecules rather than as antioxidants [Williams et al. Phytochemistry.T.L. The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. Quantitative kinetic analysis of hydrogen transfer reactions from dietary polyphenols to the DPPH radical.J.. Hollman P. Harborne J. Struct.. 32...B. Meyer A. Erkoc F. 26.. 13.. 25. 59. 2005. 2006. London. Wu Ch. 24.P. 2003.. 2774–2779. Loonis M. Day A. Food Chem. Lin Y. Giaccherini C.. Prod. Manach C. Blumberg J..A. 88. 2006. Alfthan G..C.). 61. Life Sci. Cancer.K. REFERENCES 1..V... Innocenti M. Parantainen J.O. 136. 2004. Advances in Research Since 1986. 28.K. J. Kalinova J. 378–382. 809–816... 51. 223. On the  other hand.dependent and –independent apoptosis in rat glioma C6 cells..) cultivars for their contents of  flavonol O. Food Chem.. Dangles O. 47. Triska J..... Quercetin glucosides interact with the intestinal glucose transport pathway. Chang Q.H. but not its glycosides is absorbed from the rat stomach.. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers.and xanthone C-glycosides. Dolnikowski G. Antioxidant and antiradical activities of flavonoids.T. 2006. Shetty K. J. Kim D.. 5.H...and CCl4 –induced hepatotoxicity in  rodents.M.M. Bartosz G.. Jeng J.

Remesy Ch. Miller J. Williams Ch.. 39. 81–86. Williamson G.. 642–647... Simmonds M. Giske N. Planta Medica (in press). Rogoliński J. 72. 53... 832.... Revisions received October 2007 and February 2008. Nutr. 2001. 2004. Grayer R. J. 38.H. 51. Kwon H. Piacente S. Food Nutr. 64. 18. Allen M. Materska M... Ryan D. Cogrel P. Med. Food Chem.D. 570–578. 69.. Datta N..Quercetin and its derivatives – a review 413 54.. Pelzer L.J. 51.. J. Proc.K. Robards K.. Agric... 2000. Lamaison J-L. Flavonoids from black chokeberries. Mazza G. 13.. Wu M. Role of  proline-linked pentose phosphate pathway in biosynthesis of plant phenolics for functional food and environmental applications: a review. Manach C.W.... Sanommiya M. Prior R. 1996.... Bioactivity and analysis of biofenols recovered from olive mill waste. Smith-Palmer A... A. Flavonoids. 159–168. 54. Fraisse D... Hung J. Crit. Shetty K.. Papyriflavonol A. Pharmacol. Scalbert A. Agric. Pharmacother.. 47.J. accepted February 2008..... 47–53. Russo G.E.. 13/54... 2002. Sci. 44. Biochem. Scalbert A. 829–837.. Cillard J. J. Dietary intake and bioavailability of polyphenols. 61–68. Nemeth K. Nutr. Odhav B.W.R.Ch..S..W.. Ecol. Pasdeloup N.. Piskuła M. Amouroux P. 502–509. 9798–9804. 276–282. Distinctive antioxidant and antiinflammatory effects of flavonols. 2073–2085.S.. 2003. Pharm. 57. Ślosarek K.. 48.E. Stochmal A. 48.. Materska M. Williams R. Rock E.. Kang S.. Free Rad.... 62. Res. 533–544.. Isolation and structure elucidation of two new flavonoid glycosides from the infusion of  Maytenus aquifolium leaves. 26.. Anthocyanins and other flavonoids. 44. Chem.C. Vilegas W. 2003.. 630–635. Ther... 2003. 36. 60. Agric. Prenzler P. 41. 2003. 42. Reddy L. Agric. Stockman R. Nicolle C. Use of phenolic compounds for sensitizing Listeria monocytogenes to  high-pressure processing.. Env. a new prenylated flavonol from Broussonetia papyrifera. 2004. Bedgood N. 1993.. Trends Plant Sci..K. 43. 13–19. 56. Carnat A.. Nutr. Effect of 3-O-glycosylation of quercetin in 3-O rhamnosidic derivative on superoxide radical scavenging activity and reduction of DNA damages after X-ray radiation of human lymphocytes. Quercetin-3-glucoside is transported by the  glucose carrier SGLT1 across the  brush border membrane of rat small intestine. 47. Food Chem. J. Pol. Bioch.. 37. Food Comp.D.. Agric. Morel I. Food Chem. Prod. Clin. 2003.. Yen J.. 87–96. 45. 1999. 2000. 70. Rev. Chang H. 61.. 55. Pharmacol.J.. Michel H. Bronowicka Ostra. Received June 2007. Natural products for cancer prevention: a  global perspective. Agric. Turek E. J. 1997. Martos I.E. Agric.L. Effects of  quercetin and quercetin-3-O-glycosides on oxidative damage on rat C6 glioma cells. Torskangerpoll K.. 456–458.. 2007. Food Microbiol. Flavonoids and antioxidative activities in buckwheat.. Antioxidant and iron-chelating activities of  the  flavonoids catechin. Slimestad R. Relationships between phenolics and soil microorganisms in spruce forests: significance for natural regeneration. Vurma M.. 2004.. 2005b.. Tox. 2003.S. Ferreres F. 63. Pizza C. 49. 58. Murthy C. Comparative study of  flavonoids in  experimental models of inflammation. De la Rocha N.. Wang S.. Flavonoids: antioxidants or signalling molecules? Free Rad. 59.T.. 463–470... 245–252. Food Chem.. Biol.J. 99–113. Food flavonoids. Oomah B. Phytochemistry. Juarez A.. 2005. processing. Shellhammer T. 152–159. Pellissier F. Antioxidant properties of phenolic compounds.. 1999.P. Tomas-Barberan F.. 823–837. Food Sci. Kim H. 2002.. Son K. Johannessen T. Paganga G. 601–606. 40. 36. Absorption and metabolism of  flavonoids. 789–803. 2004. Chiapusio G. Pharm. Zeng W. Chrom. 74. . Chung Y. 81.. Lavee S. 67. 4.. Biomed...K.. 2003. Ader P... Anal.. Fyfe L.. Am. Med. 47. 3114–3119.. Rice-Evans C..A. J. 84.K. J. Nutr.. Int.. 403–406.. Nakamura S. Perucka I. Ins and outs of  dietary phytochemicals in  cancer chemoprevention... 53. Biol.. Walle T. 132. 53.. Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in  vitro models. 2005a.Y. J. Evaluation of the antiulcer activity of the infusion. Nat.S. Lian T. Cillard P..... Yao L. Agric. Jayaprakasha G. 263–269. Zielińska M. Determination of phenolic compounds in  olives by reversed-phase chromatography and mass spectrometry.. 2006. Piskuła M. J. Rice-Evans C. Absorption and metabolism of polyphenols in the gut and impact on health. 50. Souto X. Importance of flavonoids in insect-plant interactions: feeding and oviposition. 36.J.... Gülden M. Food Nutr. 66... 2. Oxygen radical absorbing capacity of phenolics in  blueberries. Obied H. 2006. Food Chem. J. Fitoterapia... Oleszek W.. Nateland H. Food content. 72–76. Tu Y.. 130. Quantitative and qualitative determination of  flavonoids and phenolic acid derivatives from pericarp of  hot pepper fruit cv. Rep. J. 12/53. Food Microbiol..L. Food Chem. Pol. 2000.. Antimutagenic activity of  flavonoids from Pogostemon cablin. 56. 2025–2034. 2004.E. 101–114. Remesy Ch.. 2004. J. Wang L. Stewart J.. Sergent O. 78. 52... 2007.. 2002. 50. 56... 68... Blöck M. cranberries. Food Agric. Food Chem. 838–849. Miyazawa M. Kosaka H.D. 48. Characterisation and variation of antioxidant micronutrients in lettuce (Lactuca sativa folium).P. Sci. 106. 539–573.. J.. Singh R. Food Chem... J. Konopacka M. Guardia T.. J.. Verheul M. Perucka I.... Robards K.. Bhoola K.H. Brissot P.. Pharmacol.H. chokenberries and lingonberries. Wolfram S. Fruits and vegetables in the prevention of cellular oxidative damage.. quercetin and diosmetin on ironloaded rat hepatocyte cultures. 21. 45. 46.. Singanusong R. The potential application of plant essential oils as natural food preservatives in soft cheese.. 1746–1750. J. 2061–2069.E. Lescoat G. Rotelli A. Spencer P...N. Seibert H. J.. Morand Ch.. Okuno Y. J. Sci. Aronia melanocarpa. 39.O. absorption and metabolism of onion flavonoids. Wiczkowski W.A. Slimestad R.A. Seasonal variations in  the  level of plant constituents in greenhouse production of Cherry tomatoes. Bioch.... 18. 65. Yousef A. phenolic acids and abscisic acid in  Australian and New Zeland Leptospermum honeys.. Food Chem. Rastrelli L.K.. 2001... 2001.H.J.K. 397–409..