Berry Flavonoids and Phenolics: Bioavailability and Evidence of Protective Effects
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Downloaded from British Journal of Nutrition (2010), 104, S67–S90 doi:10.1017/S0007114510003958 q The Authors 2010 https://www.cambridge.org/core Berry flavonoids and phenolics: bioavailability and evidence of protective effects Daniele Del Rio1, Gina Borges2 and Alan Crozier2* . IP address: 1Human Nutrition Unit, Department of Public Health, University of Parma, Via Volturno 39, 43100 Parma, Italy 2Plant Products and Human Nutrition Group, School of Medicine, College of Medical, Veterinary and Life Sciences, Graham Kerr 170.106.202.8 Building, University of Glasgow, Glasgow G12 8QQ, UK (Received 25 January 2010 – Accepted 24 February 2010) , on 24 Sep 2021 at 06:36:04 Berries contain vitamin C and are also a rich source of phytochemicals, especially anthocyanins which occur along with other classes of phenolic compounds, including ellagitannins, flavan-3-ols, procyanidins, flavonols and hydroxybenzoate derivatives. This review examines studies with both human subjects and animals on the absorption of these compounds, and their glucuronide, sulphate and methylated metabolites, into the cir- culatory system from the gastrointestinal tract and the evidence for their localisation within the body in organs such as the brain and eyes. The involvement of the colonic microflora in catabolising dietary flavonoids that pass from the small to the large intestine is discussed along with the potential fate and role of the resultant phenolic acids that can be produced in substantial quantities. The in vitro and in vivo bioactivities of these , subject to the Cambridge Core terms of use, available at polyphenol metabolites and catabolites are assessed, and the current evidence for their involvement in the protective effects of dietary polyphenols, within the gastrointestinal tract and other parts of the body to which they are transported by the circulatory system, is reviewed. Dietary polyphenols: Bioavailability: Metabolism: Matrix effects: Protective effects Flavonoids and phenolic compounds in berries and other and it has been used in taxonomy, as well as for the detection selected fruits of adulteration of juices and wines. Blackcurrants are charac- terised by the presence of the rutinosides and glucosides of Berries contain vitamin C and are a rich source of phytochem- delphinidin and cyanidin, with the rutinosides being the icals, in particular anthocyanins. They also contain most abundant. Other anthocyanins occur but at much lower ellagitannins, flavan-3-ols, procyanidins, flavonols and hydro- concentrations. While redcurrants are very closely related to xybenzoate derivatives. The anthocyanins are conjugated British Journal of Nutrition blackcurrants, they contain mainly cyanidin diglycosides anthocyanidins, which provide the distinctive and vibrant pal- with cyanidin monoglucosides present only as minor com- https://www.cambridge.org/core/terms ette of colours found in berries. There are six main anthocya- ponents. Strawberries (Fragaria £ ananassa), blackberries nidins distributed throughout the plant kingdom: cyanidin, (Rubus spp.) and red raspberries (R. idaeus) are all from the malvidin, delphinidin, peonidin, petunidin and pelargonidin Rosaceae family but they have a diverse anthocyanin content. (Fig. 1). They form O-linked conjugates with a number of The major anthocyanins in raspberries and blackberries are sugars, in particular glucose, sophorose, rutinose, rhamnose, derivatives of cyanidin, while in strawberries, pelargonidin- galactose, arabinose and xylose. 3-O-glucoside predominates. The major components in blue- Concentrations of phytochemicals in berries will be influ- berries are malvidin-3-O-arabinoside and the 3-O-galactosides enced by many factors including environmental conditions, of cyanidin, delphinidin, petunidin and malvidin, with many degree of ripeness, cultivar, cultivation site, processing and minor anthocyanins also being present. Cranberries belong storage of the fruit(1 – 3). The structures of the predominant to the Ericaceae, the same family as blueberries, but have cya- . anthocyanins are summarised in Fig. 2 and are listed in nidin- and peonidin-based compounds as their major antho- https://doi.org/10.1017/S0007114510003958 more detail along with other flavonoids and phenolic com- (4 – 16) cyanins (Table 1, Fig. 2). pounds in Table 1 . There is much variety, and while Flavonols and other flavonoids are commonly quantified as some fruits, such as redcurrants (Rubus idaeus) and elderberry the aglycone after acid or enzyme hydrolysis to remove sugar (Sambucus nigra), contain derivatives of only one type of residue(17,18). Using this approach, the myricetin, quercetin anthocyanin (i.e. cyanidin), a wide array of anthocyanins is and kaempferol content of edible berries had been esti- found in blueberry (Vaccinium corymbosum), bilberry mated(19). Quercetin was found to be highest in bog whortle- (Vaccinium myrtillus) and blackcurrant (Ribes nigrum). In berry (Vaccinium uliginosum) (158 mg/kg) and bilberry general, the anthocyanin profile of a tissue is characteristic, (17–30 mg/kg). In blackcurrant cultivars, myricetin was the Abbreviations: Cmax, peak plasma concentration; Tmax, maximum time. * Corresponding author: A. Crozier, fax þ44 141 3305394, email [email protected] Downloaded from S68 D. Del Rio et al. R1 A variety of hydroxycinnamates, including chlorogenic https://www.cambridge.org/core 3′ OH acids, are also found in berries but usually they are present in low concentrations(24), although in other fruits, including HO 7 O+ 5′ R apples, 5-O-caffeoylquinic acid can accumulate in more sub- 2 stantial concentrations. Concord purple grapes (Vitis labrusca) 5 3 OH contain the hydroxycinnamate–tartaric acid conjugates couta- OH ric acid and caftaric acid (Fig. 7)(23). IP address: Anthocyanidin R1 R2 Colour Bioavailability of flavonoids and phenolic compounds Pelargonidin H H Orange-red Following the ingestion of dietary flavonoids which, with the notable exception of flavan-3-ols, exist in planta predomi- 170.106.202.8 Cyanidin OH H Red nantly as glycoside conjugates, absorption of some but not Delphinidin OH OH Pink all components into the circulatory system occurs in the small intestine(25). Typically, this is associated with hydroly- Peonidin OCH3 H Bluish purple sis, releasing the aglycone, as a result of the action of lactase , on phloridizin hydrolase in the brush border of the small intestine 24 Sep 2021 at 06:36:04 Petunidin OCH3 OH Purple epithelial cells. Lactase phloridizin hydrolase exhibits broad substrate specificity for flavonoid-O-b-D-glucosides, and the Malvidin OCH OCH Redish purple 3 3 released aglycone may then enter the epithelial cells by passive diffusion as a result of its increased lipophilicity and Fig. 1. Anthocyanidin structures. its proximity to the cellular membrane(26). An alternative site of hydrolysis is a cytosolic b-glucosidase within the epi- , subject to the Cambridge Core terms of use, available at most abundant flavonol (89–203 mg/kg), followed by thelial cells. In order for cytosolic b-glucosidase-mediated quercetin (70–122 mg/kg) and kaempferol (9–23 mg/kg). In hydrolysis to occur, the polar glucosides must be transported comparison, the total anthocyanin content of red raspberries into the epithelial cells, possibly with the involvement of the is approximately 600 mg/kg(11,12). Specific flavonol glycosides active Na-dependent GLUT-1(27). Thus, it has been accepted that have been identified in berries include quercetin-3-O- that there are two possible routes by which the glucoside con- glucoside, quercetin-3-O-rutinoside, quercetin-3-O-galactoside jugates are hydrolysed, and the resultant aglycones appear in and quercetin-3-O-xylosylglucuronide, myricetin-3-O-gluco- the epithelial cells, namely ‘lactase phloridizin hydrolase/ side, myricetin-3-O-galactoside and myricetin-3-O-rutinoside diffusion’ and ‘transport/cytosolic b-glucosidase’. However, (Fig. 3, Table 1). a recent investigation, in which Na-dependent GLUT-1 was Berries can contain the flavan-3-ol monomers (þ)-catechin expressed in Xenopus laevis oocytes, indicated that SLGT1 and (2)-epicatechin as well as dimers, trimers and polymeric does not transport flavonoids and that glycosylated flavonoids, proanthocyanidins (Fig. 4). The concentration of the polymers and some aglycones, have the capability to inhibit the GLUT(28). is usually greater than the monomers, dimers and trimers, and Before passage into the bloodstream, the aglycones undergo British Journal ofoverall Nutrition cranberries are a particularly rich source of these com- metabolism forming sulphate, glucuronide and/or methylated (5,20) pounds (Table 2) . metabolites through the respective action of sulphotrans- https://www.cambridge.org/core/terms The hydroxybenzoate, ellagic acid (Fig. 5), has been ferases, UDP-glucuronosyltransferases and catechol-O-meth- reported in berries, particularly raspberries (5·8 mg/kg), straw- yltransferases. There is also efflux of at least some of the berries (18 mg/kg) and blackberries (88 mg/kg)(21). Indeed, metabolites back into the lumen of the small intestine, and ellagic acid has been described as being responsible this is thought to involve members of the ATP-binding for . 50 % of total phenolics quantified in strawberries and cassette family of transporters including multidrug resistance raspberries(22). In reality, however, free ellagic acid levels protein and P-glycoprotein. Once in the bloodstream, metab- are generally low, although substantial quantities are detected olites can be subjected to phase II metabolism