**2. The constituents of pomegranate and derived products**

Along with olives, figs and grapes, pomegranates are among the first plants to have been cultivated by man. Pomegranate (*Punica granatum* L.) is considered one of the oldest known edible fruit that is mentioned in the Koran, the Bible, the Jewish Torah, and the Babylonian Talmud as 'Food of Gods' that is symbolic of plentyness, fertility and prosperity (Madihassan, 1984; Aviram et al., 2000; Seeram et al., 2006). The pomegranate, a mystical and highly distinctive fruit, is the predominant member of two species comprising the *Punicaceae* family. The genus name Punica, was the Roman name for Carthage, where the best pomegranates were known to grow. Pomegranate is known by the French as grenade, the Spanish as granada (derived from the ancient city of Granada), and literally translates to seeded ("granatus") apple ("ponium") (Jurenka, 2008).

In ancient Greek mythology, the edible part of pomegranate known as the "fruit of the dead", containing considerable amounts of saccharides, polyphenol, and available in Hades for its residents. Hades benefitted amorously when six pomegranate seeds from his kingdom sealed for him the betrothal of the daughter of Zeus and Demeter. The

The Therapeutic Potential of Pomegranate and Its Products for Prevention of Cancer 333

Pomegranate juice Anthocyanins; glucose; ascorbic acid; phenolics such as

Pomegranate leaves Ellagitannins (punicalin and punicafolin); flavonols such as luteolin and apgenin Pomegranate flower Gallic acid, triterpenoids such as ursolic,maslinic and

About 50% of the total fruit weight corresponds to the peel, which is an important source of bioactive compounds such as phenolics, flavonoids, ellagitannins (ETs), and proanthocyanidin compounds (Li et al., 2006), minerals (Mirdehghan & Rahemi, 2007), and complex polysaccharides (Jahfar et al., 2003). Significant variations in organic acids, phenolic compounds, sugars, water-soluble vitamins, and minerals of pomegranates have been

The edible part of the pomegranate fruit consists of 40% arils and 10% seeds. The arils are comprised of approximately 80% juice and 20% seed. The juice of arils contain 85% water, 10% total sugars (glucose, sucrose, and fructose) (Melgarejo & Artes, 2000), and 1.5% pectin, organic acids (citric, malic, tartaric, succinic, fumaric, ascorbic acid) (Tezcan et al., 2009), fatty acids (i.e. conjugated linoleic acid, linoleic acid, punicic acid and eleostearic acid) (Fadavi et al., 2006) and amino acids (i.e. proline, valin, and methionine) (Seppi & Franciosi, 1980), and bioactive compounds (phenolics and flavonoids) (Dahham et al., 2010). Pomegranate fruit is a rich source of two types of polyphenolic compounds: anthocyanins and hydrolyzable tannins, which account for 92% of the antioxidant activity of the whole fruit (Gil et al., 2000). The soluble polyphenol content in pomegranate juice varies between 0.2 and 1.0% depending on variety (Narr Ben et al., 1996). The seeds are a rich source of lipids; of which comprised to 12% to 20% of total seed weight and characterized by a high content of polyunsaturated (*n*-3) fatty acids such as linolenic, linoleic, and other lipids such as punicic acid, oleic acid, stearic acid, and palmitic acid (Ozgul-Yucel, 2005). The seeds also contain protein, crude fibers, vitamins, minerals, pectin, sugars, polyphenols, isoflavones (mainly genistein), the phytoestrogen coumestrol, and the sex steroid, estrone (Singh et al.,

Pomegranate flowers (*gulnar*) contain a variety of secondary metabolites: i) polyphenols, including gallic acid (Huang et al., 2005b), ellagic acid and ethyl brevifolin-carboxylate (Wang et al., 2006), and ii) triterpene acids consisting of oleanolic, ursolic (Huang et al., 2005a), maslinic and asiatic (Batta & Rangaswami, 1973). In folk medicine the decoction of flowers is used to stop bleeding and purging (Sivarajan & Balachandran, 1994; Jafri et al.,

Pomegranate seed oil Punicic acid; ellagic acid; fatty acids; sterols

flavonoids

asiatic acid

Pomegranate roots and bark Ellagitannins; piperidine alkaloids

reported by various researchers (Davidson et al., 2009; Tezcan et al., 2009).

1990; Singh & Sethi, 2003; El-Nemr et al., 2006; Syed et al., 2007).

Table 2. Phytochemicals of Pomegranate (Jurenka, 2008).

mineral elements; aminoacids

ellagic acid, gallic acid, caffeic acid, catechin, epigallocatechin gallate (EGCG), quercetin, rutin;

Phenolic compounds like punicalagins, gallic acid, catechin, EGCG, quercetin, rutin, anthocyanidins, other

Plant Component Constituents

Pomegranate pericarp (peel,

rind)

Babylonians regarded the seeds as an agent of resurrection, the Persians as conferring invincibility on the battle field and for ancient Chinese alchemical adepts; the bright red juice was mythopoetically regarded as a "soul concentrate", a synonym to human blood, conferring to longevity and immortality (Dahham et al., 2010). Since ancient times, the pomegranate has been used extensively in the folk medicine of many cultures as a "healing food" in order to eliminate parasites, as an antihelmintic and vermifuge, antipyretic, and to treat and cure aphtae, ulcers, diarrhea, acidosis, dysentery, hemorrhage, microbial infections, and respiratory pathologies. It also features prominently in the ceremonies, art, and mythology of the Egyptians and Greeks, and was the personal emblem of Maximilian, the Holy Roman Emperor (Longtin, 2003; Larrosa et al., 2010; Lee et al., 2010).

The pomegranate fruit is round, with leathery skin or rind, typically yellow, overlaid with light or deep pink or rich red. The edible part of the fruit, the arils can be preserved as syrup or used for juice, jam, jelly, wine, vinegar, and fruit leather production, and can be an alternative to flavoring and coloring used in beverages (Maestre et al., 2000; Fadavi et al., 2005; Ozgen et al., 2008; Al-Said et al., 2009; Mousavinejad et al., 2009; Akbarpour et al., 2010).

#### **2.1 Chemical composition of pomegranates**

The pomegranate tree can be divided into several anatomical compartments: seed, juice, peel, leaf, flower and root bark, each of which is widely used in therapeutic and food formulas, and cosmetics due in large part to the scientifically supported health benefits on arteriosclerosis, cholesterol levels and cancer prevention.The other parts are good source of tannins, dyes, and alkaloids (Khan, 2009; Viuda-Martos et al., 2010; Wang et al., 2010). The chemical composition of the pomegranate and its products depends on the cultivar, growing region, and climate, the fruit's stage of maturity, cultural practices and manufacturing systems (Badenes et al., 1998; Dumas et al., 2003; Toor et al., 2006; Raffo et al., 2006, Borochov-Neori et al., 2009; Zarei et al., 2011). Tables 1 & 2 show the chemical composition of pomegranate fruit and phytochemicals in pomegranate and its parts.


\*Values per 100 g of edible portions

Table 1. Chemical Composition of Pomegranate\* (Yilmaz, 2007).

Babylonians regarded the seeds as an agent of resurrection, the Persians as conferring invincibility on the battle field and for ancient Chinese alchemical adepts; the bright red juice was mythopoetically regarded as a "soul concentrate", a synonym to human blood, conferring to longevity and immortality (Dahham et al., 2010). Since ancient times, the pomegranate has been used extensively in the folk medicine of many cultures as a "healing food" in order to eliminate parasites, as an antihelmintic and vermifuge, antipyretic, and to treat and cure aphtae, ulcers, diarrhea, acidosis, dysentery, hemorrhage, microbial infections, and respiratory pathologies. It also features prominently in the ceremonies, art, and mythology of the Egyptians and Greeks, and was the personal emblem of Maximilian,

The pomegranate fruit is round, with leathery skin or rind, typically yellow, overlaid with light or deep pink or rich red. The edible part of the fruit, the arils can be preserved as syrup or used for juice, jam, jelly, wine, vinegar, and fruit leather production, and can be an alternative to flavoring and coloring used in beverages (Maestre et al., 2000; Fadavi et al., 2005; Ozgen et

The pomegranate tree can be divided into several anatomical compartments: seed, juice, peel, leaf, flower and root bark, each of which is widely used in therapeutic and food formulas, and cosmetics due in large part to the scientifically supported health benefits on arteriosclerosis, cholesterol levels and cancer prevention.The other parts are good source of tannins, dyes, and alkaloids (Khan, 2009; Viuda-Martos et al., 2010; Wang et al., 2010). The chemical composition of the pomegranate and its products depends on the cultivar, growing region, and climate, the fruit's stage of maturity, cultural practices and manufacturing systems (Badenes et al., 1998; Dumas et al., 2003; Toor et al., 2006; Raffo et al., 2006, Borochov-Neori et al., 2009; Zarei et al., 2011). Tables 1 & 2 show the chemical composition

the Holy Roman Emperor (Longtin, 2003; Larrosa et al., 2010; Lee et al., 2010).

al., 2008; Al-Said et al., 2009; Mousavinejad et al., 2009; Akbarpour et al., 2010).

of pomegranate fruit and phytochemicals in pomegranate and its parts.

Moisture 72.6-86.4% Protein 0.05-1.6% Fat 0.01-0.9% Mineral elements 0.36-0.73% Fibre 3.4-5.0% Carbohydrates 15.4-19.6% Calcium 3.0-12.0 mg Phosphorus 8.0-37.0 mg Iron 0.3-1.2 mg Sodium 3.0 mg Magnesium 9.0 mg Ascorbic acid (Vitamin C) 4.0-14.0 mg Thiamine (Vitamin B1) 0.01 mg Riboflavine (Vitamin B2) 0.012-0.03 mg Niacine 0.18-0.3 mg

Table 1. Chemical Composition of Pomegranate\* (Yilmaz, 2007).

**2.1 Chemical composition of pomegranates** 

Constituent

\*Values per 100 g of edible portions


Table 2. Phytochemicals of Pomegranate (Jurenka, 2008).

About 50% of the total fruit weight corresponds to the peel, which is an important source of bioactive compounds such as phenolics, flavonoids, ellagitannins (ETs), and proanthocyanidin compounds (Li et al., 2006), minerals (Mirdehghan & Rahemi, 2007), and complex polysaccharides (Jahfar et al., 2003). Significant variations in organic acids, phenolic compounds, sugars, water-soluble vitamins, and minerals of pomegranates have been reported by various researchers (Davidson et al., 2009; Tezcan et al., 2009).

The edible part of the pomegranate fruit consists of 40% arils and 10% seeds. The arils are comprised of approximately 80% juice and 20% seed. The juice of arils contain 85% water, 10% total sugars (glucose, sucrose, and fructose) (Melgarejo & Artes, 2000), and 1.5% pectin, organic acids (citric, malic, tartaric, succinic, fumaric, ascorbic acid) (Tezcan et al., 2009), fatty acids (i.e. conjugated linoleic acid, linoleic acid, punicic acid and eleostearic acid) (Fadavi et al., 2006) and amino acids (i.e. proline, valin, and methionine) (Seppi & Franciosi, 1980), and bioactive compounds (phenolics and flavonoids) (Dahham et al., 2010). Pomegranate fruit is a rich source of two types of polyphenolic compounds: anthocyanins and hydrolyzable tannins, which account for 92% of the antioxidant activity of the whole fruit (Gil et al., 2000). The soluble polyphenol content in pomegranate juice varies between 0.2 and 1.0% depending on variety (Narr Ben et al., 1996). The seeds are a rich source of lipids; of which comprised to 12% to 20% of total seed weight and characterized by a high content of polyunsaturated (*n*-3) fatty acids such as linolenic, linoleic, and other lipids such as punicic acid, oleic acid, stearic acid, and palmitic acid (Ozgul-Yucel, 2005). The seeds also contain protein, crude fibers, vitamins, minerals, pectin, sugars, polyphenols, isoflavones (mainly genistein), the phytoestrogen coumestrol, and the sex steroid, estrone (Singh et al., 1990; Singh & Sethi, 2003; El-Nemr et al., 2006; Syed et al., 2007).

Pomegranate flowers (*gulnar*) contain a variety of secondary metabolites: i) polyphenols, including gallic acid (Huang et al., 2005b), ellagic acid and ethyl brevifolin-carboxylate (Wang et al., 2006), and ii) triterpene acids consisting of oleanolic, ursolic (Huang et al., 2005a), maslinic and asiatic (Batta & Rangaswami, 1973). In folk medicine the decoction of flowers is used to stop bleeding and purging (Sivarajan & Balachandran, 1994; Jafri et al.,

The Therapeutic Potential of Pomegranate and Its Products for Prevention of Cancer 335

juices in Turkish market were a good source for minerals such as potassium (1283.30 mg/L), calcium (107.53 mg/L), sodium (96.02 mg/L), phosphorus (76.54 mg/L) and magnesium (67.22 mg/L). The high mineral content of pomegranate juices could contribute to the daily

Pomegranate can be consumed as fresh, fruit juice, fermented fruit juice, dried aril, frozen aril, minimally-processed aril, canned aril, jam, jelly, wine, vinegar, paste, fruit leather and

Pomegranate arils can either be consumed fresh or procesed (dried, frozen, canned and minimally-processed). The conventional utilization of wild pomegranate fruit lies in the drying seeds along with pulp (arils), which constitute a traditional product called as '*Anardana*' (Pruthi & Saxena, 1984). The dehydrated arils are acidic (7.8–15.4%), help in improving mouth-feel and digestion, and are widely used as acidulent in culinary preparations. The dried anardana contains acid (5.8-15.4%), total sugars (9.3-17.5%) and crude fiber as compared to fresh fruit. To obtain frozen arils the arils are put into polyethylene bags either with syrup of 15° Brix or coated with solid sugar and frozen in a chest freezer. For canned arils, used generally as an appartiser, the arils were put into metal tins with syrup of 15° Brix and sterilised for 10 minutes. In the production of minimallyprocessed pomegranate aril pomegranates are chilled to 0°C, selected, washed and dried with a current of air at room temperature. They are conditioned in polyethylene bags that were heat-sealed and conserved in a chamber at 0°C for 10-15 days. These arils are used as a

Pomegranate juice can be extracted by using a spiral-type screw press without crushing the seeds. The juice is clarified by heating in a flash pasteurizer at 79-82°C cooling, settled for 24 hours and filtered. The clear juice can be preserved by heat treatment or by using chemicals. The use of sulphur dioxide is banned for pomegranate due to loss of colour by bleaching action of SO2. Pomegranate juice represents one of the foods recently promoted for its health benets since a glass of pomegranate juice contains about 40% of the Recommended Daily

Pomegrenate syrup of 60° Brix with an added acidity of 1.5% as citric acid has a bright purplish-red colour and a delightful taste and flavour. It was preserved by pasteurization. Preparation of jelly on a small-scale from sweet-sour pomegranates is described by Adsule et al. (1992) and Singh & Singh (2004). When making the jellies, approximately 50% of the total anthocyanins present in the juice of are lost. During storage at 5°C, certain colour differences were observed, which indicates that the pH was not the only parameter

For preparation of wine, the whole furits are pressed without crushing or juice may be extracted from pomegranate grains, which gives a yield of 76 to 85% (Adsule & Patil, 1995). Sugar is added to the juice to obtain 22-23° Brix. The juice is fermented as in the same manner of red grape wine. The wine is flash pasteurized at 60°C and bottled hot (Singh &

Pomegranate seed is a residue obtained from pomegranate juice production, ranging between 40 and 100 g/kg of fruit weight (Fadavi et al., 2006; Lansky & Newman, 2007). The

intake of these constituents in the human diet.

garnish for desserts and salad (Al-Maiman & Ahmad, 2002).

Allowance (RDA) of Vitamin C (Singh & Singh, 2004).

responsible for this characteristic.

Singh, 2004).

**2.2 Pomegranate fruit derived products** 

in flavoring products.

2000). The polyphenols in pomegranate flowers have strong antioxidant activity (Oswa et al., 1987); ellagic acid had a marked inhibitory effect on the occurrence and development of tumours in mice (Boukharta et al., 1992), triterpenes show antimutagenic and anticarcinogenic effects (Ovesná et al., 2004); and oleanolic acid significantly enhanced acute glucose-stimulated insulin secretion at basal and stimulatory glucose concentrations in pancreatic b-cell , and such effects may contribute to the antidiabetic properties (Teodoro et al., 2008).

Pomegranate fruit extracts/constituents possesses immense biological activities such as anticarcinogenic (Whitley et al., 2003; Afaq et al., 2005), antibacterial (Akiyama et al., 2001; Prashanth et al., 2001; Duman et al., 2009), antidiarrhoeal (Das et al., 1999), antifungal (Dutta et al., 1998), antiulcer (Gharzouli et al., 1999), antioxidant activity and free radical scavenging capability (Schubert et al., 1999; Aviram et al., 2000; Festa et al., 2001), strengthening of the immune system (Lee et al., 2008), prevention of heart disease (Johanningsmeier & Harris, 2011) and liver fibrosis (Thresiamma & Kuttan, 1996), and inhibition of lipid peroxidation even at lower concentrations than vitamin E (Rosenblat et al., 2003). All these therapeutical activities are related to the presence of diverse '*phenolic compounds'*, including gallic acid, protocatechinunic acid, chlorogenic acid, caffeic acid, ferulic acid, coumaric acid, and catechin and hydrolysable tannins (such as punicalin, pedunculagin, punicalagin, corilagin, casuarinin, punicacortein, granatin and ellagic acid), and anthocyanins (delphinidin, cyanidin and pelargonidin 3-glucosides and 3,5 diglucosides) (Amakura et al., 2000; Noda et al., 2002; Poyrazoglu et al., 2002; Kulkarni & Aradya, 2005; Viuda-Martos et al., 2010).

The bright colour of pomegranate flowers and arils is due to anthocyanins (Afaq et al., 2005); however, only one anthocyanin compound (i.e. pelargonidin-3,5-diglucoside) has yet been identified in pomegranate flowers using HPLC (Miguel et al., 2009), whereas in pomegranate juice, principally cyanidin-3-*O*-glucoside, cyanidin-3,5-di-*O*-glucoside, delphinidin-3-*O*-glucoside, delphinidin-3,5-di-*O*glucoside, pelargonidin-3-*O*-glucoside, and pelargonidin-3,5-di- *O*-glucoside, have been reported (Lansky & Newman 2007; Jaiswal et al., 2010).

Tannins, high-molecular-weight plant polyphenols, are divided into 3 chemically and biologically distinct groups: condensed tannins or proanthocyanidins, hydrolyzable tannins or elagitannins (ETs), and gallotannins (GTs) (Seeram et al., 2005). Pomegranate leaves contain unique tannins such as punicalin and punicafolin, and also have glycosides of apigenin, a avone with progestinic (Zand et al., 2000) and anxiolytic (Paladini et al., 1999) properties. Pomegranate peel are rich in hydrolyzable tannins, mainly punicalin, pedunculagin, and punicalagin (Seeram et al., 2006), which differ from proanthocyanidins in their chemical structures. In addition to ETs, pomegranate peel contains hydroxybenzoic acids such as gallagic, ergot alkaloid (EA), and EA glycosides (Amakura et al., 2000); anthocyanidins are principally cyanidin, pelargonidin, and delphinidin (Noda et al., 2002) and flavonoids such as kaempferol, luteolin, and quercetin (Van Elswijk et al., 2004).

Al-Maiman & Ahmad (2002) showed the amounts of potassium, calcium and sodium were highest in both juice and seeds followed by magnesium, phosphorous, zinc, iron and copper. The authors stated that pomegranate can be a good source of nutrients and variation could originate from the pomegranate cultivar, and agro-climatic. Akpinar-Bayizit (2010) reported that although processing steps include clarification and filtration, the pomegranate juices in Turkish market were a good source for minerals such as potassium (1283.30 mg/L), calcium (107.53 mg/L), sodium (96.02 mg/L), phosphorus (76.54 mg/L) and magnesium (67.22 mg/L). The high mineral content of pomegranate juices could contribute to the daily intake of these constituents in the human diet.
