2013 http://informahealthcare.com/ijf ISSN: 0963-7486 (print), 1465-3478 (electronic) Int J Food Sci Nutr, 2013; 64(7): 907–913 ! 2013 Informa UK Ltd. DOI: 10.3109/09637486.2013.798268 COMPREHENSIVE REVIEW The pharmacological use of ellagic acid-rich pomegranate fruit Coskun Usta 1 , Semir Ozdemir 2 , Michele Schiariti 3 , and Paolo Emilio Puddu 3 1 Department of Pharmacology, 2 Department of Biophysics, Faculty of Medicine, Akdeniz University, Antalya, Turkey, and 3 Department of Cardiovascular, Respiratory, Nephrological and Geriatrical Sciences, Laboratory of Biotechnologies Applied to Cardiovascular Medicine, Sapienza, University of Rome, Rome, Italy Abstract In recent years, the therapeutic use of non-drug substances such as herbal and medicinal foods is increasing progressively. Of these substances, Punica granatum L., which is an ancient and highly distinctive fruit, has been proposed for treatment of several different illnesses. Ellagic acid (EA) is one of those biological molecules found in pomegranate and may have therapeutic potential in many diseases. EA has been detected not only in pomegranate but also in a wide variety of fruits and nuts such as raspberries, strawberries, walnuts, grapes and black currants, and is becoming an increasingly popular dietary supplement over recent years. Similar to other ellagitannins (ETs), EA is quite stable under physiological conditions in the stomach. EA and ETs as active agents induce vasorelaxation, oxygen free radical scavenging, hypolipidemic, anti- inflammatory and anti-carcinogenic activities in various animal preparations call an attention to the need for designing adequate tests in humans to assess these potentially useful properties in diseased states. Keywords Ellagic acid, ellagitannins, polyphenols, Punica granatum L History Received 24 January 2013 Revised 8 April 2013 Accepted 15 April 2013 Published online 23 May 2013 Introduction Throughout the past decades, there has been a significantly increased use of dietary supplements such as vitamins, herbals and medicinal foods in the general population. From 1990 to 1997, more than 15 million adults in the United States reported using herbal supplements in conjunction with prescribed medica- tions (Eisenberg et al., 1998). In addition, from 1997 to 2002, there was a further increase of more than 50% in the consumption of dietary supplements (Tindle et al., 2005). The pomegranate, Punica granatum L., is an ancient, mystical and highly distinctive fruit. In addition to its historical uses, pomegranate is found in several medicinal systems for a variety of ailments. Over the past decade, significant progress has been made in establishing the pharmacological mechanisms of pom- egranate and its individual responsible constituents. Current research seems to indicate that the most therapeutic- ally beneficial pomegranate constituents are ellagitannins (ETs; including ellagic acid (EA)), punicic acid, flavonoids, anthocya- nidins, anthocyanins and estrogenic flavonols and flavones (Espı ´n et al., 2007; Quideau & Feldman, 1996). Pomegranate’s con- sumption has been associated with cardiovascular health benefits, since it contains relevant amounts of phenolic anti-oxidants, and particularly ETs, considered responsible, at least in part, for these physiological properties (Larrosa et al., 2010). These polyphenols contained in pomegranate and different fruits and nuts are described in the category of hydrolysable tannins, phytochemicals of the non-flavonoid polyphenol group, including ETs, which release EA upon hydrolysis and under the physiological conditions of the gastrointestinal tract (Falsaperla et al., 2005). EA content of several food products can be quite high. EA, a polyphenol compound found in a wide variety of fruits and nuts, such as raspberries, strawberries, walnuts, grapes, and black currants, is becoming an increasingly popular dietary supplement over the recent years because it can be easily extracted and used (Devipriya et al., 2007b). There is a relatively high content of EA in raspberries (1500 mg/g dry weight), strawberries (630 mg/g dry weight), cranberries (120 mg/g dry weight), walnuts (590 mg/g dry weight), pecans (330 mg/g dry weight) and other plant foods (Figure 1; Bala et al., 2006). Although several functions of EA are described, the mechanism of its biological functionality is not very well-understood. Commonly found in many plants, EA exhibits powerful anti- carcinogenic and anti-oxidant properties, propelling it to the forefront of pomegranate research (Hassoun et al., 2004; Priyadarsini et al., 2002; Rukkumani et al., 2004). There are promising results showing that phytochemicals may exert their benefits in the prevention and therapy of many diseases including cancer, atherosclerosis and alcoholism, partially based on their ability to quench reactive oxygen species and thereby protecting critical cellular targets (i.e. DNA, proteins and lipids) from oxidative insult (Mertens-Talcott & Percival, 2005; Murakami et al., 2002). Recently, ETs and EA appear among the topics of interest in medicine and food science. This review will concentrate on the EA and aims at pointing to the important potential characteristics of EA and ETs in pomegranate (P. granatum L.) and other fruits and nuts, from a large body of evidence in animal preparations and clinical investigations, to foster interest in pharmacological and nutritional properties that may have indeed application to human disease states. To accomplish this, Medline English literature was searched, without restrictions, for EA both in animal and human investigations. Correspondence: Coskun Usta, MD, Department of Pharmacology, Faculty of Medicine, Akdeniz University, Antalya, Turkey. Tel: +90 242-2496921. E-mail: fcusta@akdeniz.edu.tr Int J Food Sci Nutr Downloaded from informahealthcare.com by AMS on 01/27/14 For personal use only.