Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health (original) (raw)

Introduction

Ellagitannins (ETs) are bioactive polyphenols that are abundant in some fruits, nuts and seeds such as pomegranates, black raspberries, raspberries, strawberries, walnuts and almonds (Amakura et al., 2000, Clifford and Scalbert, 2000). ETs, which belong to the hydrolyzable tannin class of polyphenols, are complex derivatives of ellagic acid (EA) (Quideau & Feldman, 1996). Hydrolysis of ETs with acids or bases yields hexahydroxydiphenic acid (HHDP), which spontaneously lactonizes to EA. This reaction has been utilized for the detection and quantification of ETs as EA equivalents after acid hydrolysis of food samples (Daniel et al., 1989). Also, in the human gastrointestinal tract, ingested dietary ETs are hydrolyzed to release EA. Both ETs and EA are largely metabolized by the colon microbiota of different mammals, including rats (Cerdá, Llorach, Cerón, Espín, & Tomás-Barberán, 2003), pigs (Espín et al., 2007) and humans (Cerdá et al., 2004, Larrosa et al., 2006, Larrosa et al., 2006). In all these cases, both EA and ETs produce dibenzopyranones known as urolithin A (3,8-dihydroxy-6H-dibenzopyran-6-one) and its monohydroxylated analog known as urolithin B (Cerdá et al., 2004). Therefore, in the intestine EA seems to be transformed by lactone-ring cleavage, decarboxylation and dehydroxylation reactions (Selma, Espin, & Tomás-Barberan, 2009).

In contrast to the rather limited distribution of gallotannins in nature, ETs are typical constituents of many plant families (Niemetz & Gross, 2005). With more than 500 natural products characterized so far, ETs form the largest group of known tannins (Khanbabaee & van Ree, 2001). They also play an important role in human nutrition and are endowed with numerous biological properties, including antioxidant (Mullen et al., 2002a, Seeram et al., 2005, Zafrilla et al., 2001), anticancer (Larrosa et al., 2006, Larrosa et al., 2006, Narayanan et al., 2005), anti-atherosclerotic (Aviram et al., 2004, Yu et al., 2005), anti-inflammatory (Masamune et al., 2005), antihepatotoxic (Lin, Hsu, Lin, & Hsu, 2001), antibacterial (Akiyama, Fujii, Yamasaki, Oono, & Iwatsuki, 2001) and anti-HIV replication (Martino et al., 2004, Nonaka et al., 1990) activities.

Section snippets

Chemistry of ellagitannins and ellagic acid

The observation that many tannins can be fractionated hydrolytically into their components, for example by treatment with hot water, acids, bases or with tannases, led to the classification of such tannins as ‘hydrolyzable tannins’ (Khanbabaee & van Ree, 2001). Non-hydrolyzable oligomeric and polymeric proanthocyanidins are classified as condensed tannins (Khanbabaee & van Ree, 2001). Therefore, the term ‘hydrolyzable tannins’ includes both the gallotannins and the ETs. It should also be

Sources of ellagitannins and ellagic acid

ETs and EA are consumed constantly in fruit, seeds, and in the foods or beverages based on fruit juices and jams, etc. (Clifford & Scalbert, 2000). Berries of the family Rosaceae (cloudberry, raspberry, rose hip, and strawberry) contain high levels of EA equivalents, whereas minor levels are found in sea buckthorn (family Elaeagnaceae).

Pomegranate is a rich source in the ET punicalagin (Fig. 1). Raspberry and strawberry extracts mainly contain the ET sanguiin H-6 (Fig. 1), as well as various EA

Dietary intake of ellagitannins and ellagic acid

Polyphenols are common constituents of foods of plant origin and represent major antioxidants in our diet. Dietary intake of polyphenols was estimated at about 1

g/day by Scalbert and Williamson (2000). More recently, the mean daily intake of polyphenols in the Spanish diet was estimated between 2590 and 3016

mg/day (Saura-Calixto, Serrano, & Goñi, 2007). There is no accurate information available on dietary intake of polyphenols; only a few estimations are available in the literature and the

Metabolism of ellagitannins and ellagic acid

Although there is little information on the absorption and metabolism of ETs in humans; studies with rats, mice and Iberian pigs have contributed to shedding light on ET metabolism.

Previous studies of rat intestinal contents showed that ETs could be hydrolyzed to EA at the pH found in the small intestine and cecum (Daniel, Ratnayake, Kinstle, & Stoner, 1991). These authors suggested that the cecum microbiota could also participate in hydrolysis. Further studies on EA have found that 10% of the

Microbiota and the derived metabolites of ellagitannins and ellagic acid

ET and EA consumption is associated with the urinary excretion of dibenzopyran-6-one metabolites, mainly urolithin A and urolithin B, which are also observed in plasma as conjugates after consumption of EA derivatives (Cerda, Periago, et al., 2005). The large inter-individual variability observed in the production and excretion of these metabolites, and the fact that urolithins are excreted independently of the ET consumed, would suggest microbial involvement and their production in the colon

Biological effects of ellagitannins, ellagic acid and their derived metabolites

Like other polyphenols, ETs, EA and their derived metabolites possess a wide range of biological activities, which suggest that they could have beneficial effects on human health. ET, EA and derived metabolites have antioxidant functions, estrogenic and/or anti-estrogenic activities and anti-inflammatory and prebiotic effects.

Health and ellagitannins, ellagic acid and their derived metabolites

Epidemiological evidence indicates that ETs and EA may be protective against certain chronic diseases (Arts and Hollman, 2005, Seeram, 2008). Although discrepancies are observed between in vivo and in vitro experiments, then in vitro results often do not match the findings in the in vivo studies. This could be explained by the low bioavailability of the antioxidant ETs and EA. Moreover, both polyphenols are metabolized to urolithins, which have been reported as a less potent antioxidant

Future prospects

Evidence indicates that ETs, EA and their derived metabolites may be protective against certain chronic diseases and although recent decades have witnessed an increased understanding of some of the potential action mechanisms of ETs, EA and their derived metabolites in cancer prevention, research efforts should attempt to shed light on the action mechanisms at the cellular and molecular levels. Research focusing on nutrigenomics (effects of nutrients on the genome, proteome, and metabolome) and

Acknowledgments

Landete, J.M. has a postdoctoral contract with the research program “Juan de la Cierva” (MICINN, Spain). English text was revised by F. Barraclough.