Phoenix dactylifera L.

Food Research International 44 (2011) 1812–1822

Contents lists available at ScienceDirect

Food Research International j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / f o o d r e s

A review of the chemistry and pharmacology of the date fruits (Phoenix dactylifera L.) Manjeshwar Shrinath Baliga a,⁎, Bantwal Raghavendra Vittaldas Baliga b, Shaun Mathew Kandathil c, Harshith P. Bhat d, Praveen Kumar Vayalil e a

Department of Research and Development, Father Muller Hospital Road, Mangalore, Karnataka, 575003, India Department of Pharmacology, Father Muller Hospital Road, Mangalore, Karnataka, 575003, India Department of Biotechnology, MS Ramaiah Institute of Technology, Bangalore 560054, Karnataka, India d Research Centre, Maharani Lakshmi Ammani Women's College, Malleswaram 18th Cross, Bangalore 560012, Karnataka, India e Department of Pathology, BMRII 336, University of Alabama at Birmingham, Alabama, 35294, USA b c

a r t i c l e

i n f o

Article history: Received 2 April 2010 Accepted 6 July 2010 Keywords: Phoenix dactylifera Dates Phytochemistry Pharmacology Traditional uses

a b s t r a c t Phoenix dactylifera L., commonly known as the date palm is a primeval plant and has been cultivated for its edible fruit in the desert oasis of the Arab world for centuries. The fruits are a rich source of carbohydrates, dietary fibers, certain essential vitamins and minerals. The date pits are also an excellent source of dietary fiber and contain considerable amounts of minerals, lipids and protein. In addition to its dietary use the dates are of medicinal use and are used to treat a variety of ailments in the various traditional systems of medicine. Phytochemical investigations have revealed that the fruits contain anthocyanins, phenolics, sterols, carotenoids, procyanidins and flavonoids, compounds known to possess multiple beneficial effects. Preclinical studies have shown that the date fruits possess free radical scavenging, antioxidant, antimutagenic, antimicrobial, anti-inflammatory, gastroprotective, hepatoprotective, nephroprotective, anticancer and immunostimulant activities. This review presents a comprehensive analysis of the phytochemistry and validated pharmacological properties of date fruits and the seeds. © 2010 Elsevier Ltd. All rights reserved.

1. Introduction Phoenix dactylifera L. (synonyms Palma major Garsault and Phoenix cycadifolia Hort. Attens ex Regel) commonly known as the date palm (Picture 1) is an important plant in the scorched regions of Southwest Asia and North Africa (Al Farsi and Lee, 2008; Dowson, 1982; Zaid, 1999). The fruits which are the most commonly used part are an important source of nutrition, especially in the arid regions where due to the extreme conditions, very few plants can grow. In conversational languages dates are known as Sugar Palm (English), Nakhal (Arabic), Khajur (Hindi and Urdu), Karchuram (Tamil, Malayalam) and Karjura (Kannada) (Al-Shahib and Marshall, 2003; Zaid, 1999). Date fruits are a good source of low cost food and are an integral part of Arabian diet. For Muslims all over the world dates are of religious importance and are mentioned in many places in the Quran. They are customarily used to break the day long fast during the holy month of Ramadan (Al Farsi and Lee, 2008; Al-Shahib and Marshall, 2003; Dowson, 1982). Date palms are monocotyledon, dioecious and can grow up to an altitude of 1500 m in well-drained soils. Currently they are cultivated in the Middle East, North Africa, parts of Central and South America, ⁎ Corresponding author. Father Muller Medical College, Father Muller Hospital Road, Kankanady, Mangalore, Karnataka, 575003, India. Tel.: + 91 824 2238331 (office); fax: + 91 824 2437402, + 91 824 2436352. E-mail address: [email protected] (M.S. Baliga). 0963-9969/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.foodres.2010.07.004

Southern Europe, India and Pakistan (Al-Shahib and Marshall, 2003; Chandra et al., 1992; Dowson, 1982; Zaid, 1999). In the late 1800s some of the best varieties of dates (Medjool, Khalas, Deglet Noor) were introduced in the warm regions of southern California, Arizona and Texas from Arabia and with time the plants have naturalized to these parts of the world (Al Farsi and Lee, 2008; Dowson, 1982). As per recent information, USA today earns the highest export price for dates in the world (Al Farsi and Lee, 2008). Information also suggest that the world production of dates has increased from about 4.60 million tons in 1994 to 6.9 million tons in 2004 and expectations are that their cultivation will continue to increase (Al Farsi and Lee, 2008). 2. Dietary use of dates Date fruit consist of 70% carbohydrates, most of which is in the form of sugars. Because of this the fruits are a high source of energy and it is approximated that 100 g of the flesh can provide 314 kcal of energy (Al Farsi and Lee, 2008). Drying of date decreases the water activity and this increases the sugar concentration. Because of this the shelf life of dry dates are high and are available for extended periods of time (Al-Shahib and Marshall, 2003). The fruits are also used as a sweetener in the preparation of beer (Al-Shahib and Marshall, 2003). The date pits which are a waste product have been used for centuries in the Arab world to make caffeine-free drink. Recently, date pit powders are also marketed and are a source of choice to people

M.S. Baliga et al. / Food Research International 44 (2011) 1812–1822

1813

Picture 1. Photograph of a date palm.

preferring a non-caffeinated coffee with coffee-related flavor. Date pits are also ground and added to the feed of domesticated animals and observations suggest they are devoid of any harmful effects. Date pits are rich in protein (5.1 g/100 g), fat (9.0 g/100 g), dietary fiber (73.1 g/100 g), phenolics (3942 mg/100 g), and antioxidants (80,400 μmol/100 g) (Al Farsi and Lee, 2008), and may be of use in enhancing the nutritional value of incorporated food products (Habib and Ibrahim, 2009). 3. Varieties of dates Estimates are that based on the shape and organoleptic properties of the fruits, there are more than 600 varieties of dates (Ahmed et al., 1995; Zaid, 1999). Some of the important date varieties grown around the world are Aabel, Ajwah, Al-Barakah, Amir Hajj, Abid Rahim, Barhe, Baht, Bekreri, Bomaan, Bouhattam, Barakawi, Bireir, Deglet Noor, Dabbas, Dayri, Empress, Fard, Ftimi, Garn ghzal, Halawi, Haleema, Hayany, Iteema, Jabri, Kenta, Khadrawy, Khlas, Kenta, Kodary, Korkobbi, Khusatawi, Lulu, Maktoomi, Maghool, Manakbir, Mermilla, Medjool, Mejraf, Mishriq, Nabtat-seyf, Naptit Saif, Nefzaoui, Raziz, Rotab, Rotbi, Sagai, Smiti, Shikat alkahlas, Sagay, Shishi, Shikat alkahlas, Sokkery, Saidi, Sayir, Sekkeri, Shabebe, Sellaj, Sultana, Tagyat, Tamej, Thoory, Umeljwary, Umelkhashab, Zahidi and Bericcha Pazham (Al Noimi and Al-Amir, 1980; Al-Shahib and Marshall, 2003; Chaira et al., 2009; Chandra et al., 1992; Habib and Ibrahim, 2009). Dates are influenced by environmental conditions and this has at times led to ‘cultivars’ with similar morphological characters being given the same varietal name e.g. Khalas Oman and Khalas Bahraini (Al Noimi and Al-Amir, 1980; Fadel et al., 2006).

Picture 2. Photograph of a date fruits one single bunch (2a) and on the palm (2b).

productive palm can support up to ten bunches and yield about 100 kg of fruit (Zaid, 1999) (Picture 2b). The sweetness and texture of date fruit is closely related to the maturity and ripeness stage (Zaid, 1999). During the growth and development of the date fruit, several external and internal changes are observed with color and chemical composition. Based on the Arabic practice dates are classified in to five stages viz. Hababouk, Kimri, Khalal, Rutab and Tamar and the same terms have been internationally accepted (Al-Shahib and Marshall, 2003; Fadel et al., 2006; Zaid, 1999).

4. Date fruiting and the stages 4.1. The Hababouk stage The date palm fruits once in a year and post pollination pass through five stages of development to reach full maturity. The whole process is lengthy and takes approximately seven months. When ripe the fruit may be yellow to reddish brown in color (Picture 2a). Dates are found in clusters and each bunch may weigh about 10 kg. A fully

Is the first stage and post fertilization lasts for four to five weeks. The fruits are immature and completely covered by the calyx leaving only one sharp end of the ovary visible. The fruit in this stage is pea sized and weighs about a gram (Ahmed et al., 1995; Al Noimi and Al-

1814


Amir, 1980; Zaid, 1999; Al-Shahib and Marshall, 2003; Fadel et al., 2006) (Picture 3). 4.2. The Khimri stage (Also called green stage) The date development in this stage is the longest and lasts for a total of nine to fourteen weeks. There is a visible transition from a small berry to the characteristic oblong shape. The fruit is green in color, quite hard, with a dry weight composition of 80% moisture and 50% sugar (glucose and fructose). It is usually bitter and unsuitable for eating (Ahmed et al., 1995; Al Noimi and Al-Amir, 1980; Al-Shahib and Marshall, 2003; Fadel et al., 2006; Zaid, 1999) (Picture 3). 4.3. Khalal stage (also called as color stage) In this stage, depending on the variety, the color changes from green to greenish yellow, yellow, pink, scarlet or red. This stage extends for six weeks and the fruit is physiologically mature, hard and ripe. The fruit attains maximum weight and size at the end of this stage. A rapid increase in the sugar concentration results following decrease in the water content (around 50–85% moisture content) (Ahmed et al., 1995; Al Noimi and Al-Amir, 1980; Fadel et al., 2006; Zaid, 1999) (Picture 3). 4.4. Rutab stage (Also called soft ripe stage) This stage lasts between two to four weeks. The apex starts ripening and the texture of the fruit becomes soft. The astringency from the previous stage is gradually lost and the fruit starts acquiring brown or black color. Due to the consistent loss of moisture content the weight further decreases. There is a gain in total sugars and solids with concomitant increase in the rate of conversion of sucrose to simpler sugars (Ahmed et al., 1995; Al Noimi and Al-Amir, 1980; Fadel et al., 2006; Zaid, 1999) (Picture 3). 4.5. Tamar stage (full ripe stage or final stage in the ripening) This is the last stage of ripening and the date appears dehydrated. The semi-dry and dry dates will have nearly 50% each of sucrose and reducing sugars. On a bunch, the fruits ripen over a month and not simultaneously. In most varieties, the skin adheres to the soft flesh and wrinkles as the inner flesh shrinks. The color of the skin and of the underlying flesh darkens with time (Ahmed et al., 1995; Al Noimi and Al-Amir, 1980; Fadel et al., 2006; Zaid, 1999) (Picture 3). 5. Proximate composition of date fruits and seeds Date pulps contain easily digestible sugars (70%), mainly glucose, sucrose and fructose; dietary fibers and contain less proteins and fats (Al Farsi and Lee, 2008). They also contain vitamins like riboflavin, thiamine, biotin, folic and ascorbic acid that are essential for the body (Table 1) (Al Farsi and Lee, 2008). The pulps are rich in iron, calcium, cobalt, copper, fluorine, magnesium, manganese, potassium, phosphorus, sodium, copper, sulfur, boron, selenium and zinc (Table 1) (Al Farsi and Lee, 2008; Ali Mohamed and Khamis, 2004). Consumption of hundred grams of dates can provide over 15% of the recommended daily allowance for selenium, copper, potassium and magnesium (Al Farsi and Lee, 2008). In many varieties, potassium can be found at a concentration as high as 0.9% in the flesh while it is as high as 0.5% in some seeds. Other minerals and salts that are found in various proportions include boron, calcium, cobalt, copper, fluorine, iron, magnesium, manganese, potassium, phosphorus, sodium and zinc (Table 1). Additionally, the seeds also contain aluminum, cadmium, chloride, lead and sulfur in various proportions. Dates contain elemental fluorine that is useful in protecting teeth against decay

Table 1 Composition of the various essential nutrients and phytochemicals in dates (Al Farsi and Lee, 2008). Composition Moisture (g/100 g) Fat (g/100 g) Ash (g/100 g) Protein (g/100 g) Amino acids (mg/100 g) Alanine Arginine Aspartic acid Cysteine Glutamic acid Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Carbohydrates (g/100 g) Fructose Glucose Sucrose Fiber (g/100 g) Soluble Insoluble Total Minerals (mg/100 g) Mg Na Ca P K Mn Fe Zn Cu Se Vitamin (μg/100 g) A (Retinol) B1 (Thiamin) B2 (Riboflavin) B3 (Niacin) B6 (Pyridoxal) B9 (Folate) C (Ascorbic acid) α-Carotenoids (μg/100 g) β-Carotenoids (μg/100 g) Zeaxanthin (μg/100 g) β-Zeaxanthin (μg/100 g) Lutein (μg/100 g) Neoxanthin (μg/100 g) Phenolics (mg/100 g) Anthocyanins (mg/100 g)

Lowest reported

Highest reported

7.2 0.1 1.0 1.1

50.4 1.4 1.9 2.6

30 34 59 13 100 42 0.1 4 41 42 4 25 36 29 23 7 15 52.6 13.6 17.6 0.5

133 148 309 67 382 268 46 55 242 154 62 67 148 128 95 92 156 88.6 36.8 41.4 33.9

0.4 3.03 3.57

1.3 7.4 10.9

31.0 1.00 5.00 35.0 345.0 0.01 0.10 0.02 0.01 0.24

150 261 206 74 1287 0.4 1.5 0.6 0.8 0.4

3.0 50 60 1274 165 39 400 3.0 2.5 33.0 9.0 28.0 184 3.91 0.2

44.7 120 160 1610 249 65 16,000 3.0 146 33.0 9.0 541 381 661 1.5

(Al Farsi et al., 2005a; Al Farsi and Lee, 2008; Ali Mohamed and Khamis, 2004). When compared to the pulp, date pits contain higher quantity of protein and fat and are also high in dietary fiber (Al Farsi and Lee, 2008). Recently, Habib and Ibrahim (2009) have studied the nutritional quality (dietary fiber, proximate analysis and micronutrients) of eighteen leading varieties of date pits of the Khalas, Barhe, Lulu, Shikat alkahlas, Sokkery, Bomaan, Sagay, Shishi, Maghool, Sultana, Fard, Maktoomi, Naptit Saif, Jabri, Kodary, Dabbas, Raziz


Picture 3. Different stages of date ripening.

and Shabebe cultivated in the United Arab Emirates. The authors observed that depending on the variety, significant but variable amounts of macronutrients and micronutrients were observed among the different varieties and also that these pits are excellent sources of dietary fiber (Habib and Ibrahim, 2009). 6. Phytochemistry of date fruits and seeds The date fruit pulp is rich in phytochemicals like phenolics, sterols, carotenoids, anthocyanins, procyanidins, and flavonoids (Table 1). The ratio and concentrations of these constituents depend on the type of the fruit, stage of fruit picking, location and soil conditions. These phytochemicals also contribute to the nutritional and organoleptic properties of the fruits (Abdelhak et al., 2005; Abdul and Allaith, 2008; Al Farsi et al., 2005b; Ahmed et al., 1995; Fayadh and Al-Showiman, 1990; Hulme, 1970). In the following section each of these are addressed. 6.1. Phenolic acids Phenolic acids constitute one of the main classes of secondary metabolites and in recent years have been a subject of intense study. It contains a hydroxylated benzene ring with one or more carboxyl groups attached directly or indirectly to it (Fig. 1). Mansouri et al. (2005) analyzed the phenolic profile of seven Algerian varieties of date and observed that they contain p-coumaric, ferulic and sinapic acids, some cinnamic acid derivatives and three different isomers of 5-o-caffeoyl shikimic acid (Fig. 1). Studies with three varieties of Omani dates have shown the presence of both free (protocatechuic acid, vanillic acid, syringic acid, and ferulic acid) and bound phenolic acids (gallic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid, syringic acid, p-coumaric acid, ferulic acid, and o-coumaric acid) (Al Farsi et al. (2005b)) (Fig. 1). Comparative studies with fresh and dried Fard dates have shown that a significant increase in phenolic content ensues on drying, possibly due to the degradation of tannins and maturation of degradative enzymes at higher temperatures (Al Farsi et al., 2005b). Recently, Chaira et al. (2009) have also observed that among the common date cultivars of Tunisian, the Mermella variety had the lowest (5.73 mg/100 g fresh weight), while the Korkobbi variety had the highest phenolic content (54.66 mg/100 g fresh weight). 6.2. Sterols Sterols, or steroid alcohols are a subgroup of steroids with a hydroxyl group at the 3-position of the A-ring and are amphipathic lipids. Sterols of plants are called phytosterols and possess myriad health benefits (Liolios et al., 2008). Kikuchi and Miki (1978) analyzed the sterols of date fruit and observed that they contain cholesterol, campesterol, stigmasterol, β-sitosterol and isofucosterol (Fig. 2).

Fig. 1. Structures of phenolic acids present in dates.

1815

1816


stage and that during the ripening process, the levels of provitamin A increases slightly in the Deglet-Noor variety while in Tantebougte and Hamraya its levels decreased (Boudries et al., 2007). Analysis of the total carotenoid contents in both fresh and dried varieties of Fard, Khasab and Khalas suggest that loss of carotenoids occurs during sundrying (Al Farsi et al., 2005b).

6.4. Procyanidins Procyanidins are condensed tannins and the main precursors of blue-violet and red pigments in fruits, vegetables, nuts, seeds, flowers, and barks (Fine, 2000). Using acetone–water–acetic acid solvent extraction method, Hong et al. (2006) extracted procyanidins from Deglet Noor variety of dates in the Khalal stage of maturity. Chemical analysis suggests that the procyanidin existed as higher molecular weight polymers, undecamers through heptadecamers, and decamers (Hong et al., 2006) (Fig. 4).

6.5. Flavonoids

Fig. 2. Structures of sterols present in dates.

6.3. Carotenoids Carotenoids are a class of natural fat-soluble pigments, and impart bright coloration to the plants. They are an important source of vitamin A and protect the cell from the deleterious effects of free radicals by acting as antioxidants (Di Mascio et al., 1991). Studies have also shown that dates contain the carotenoids; lutein, β-carotene and neoxanthin (Boudries et al., 2007) (Fig. 3). In the Algerian fresh date varieties of Deglet Noor, Tantebouchte and Hamraya, the β-carotene content is reported to be 6.4, 3.3 and 2.5 μg/100 g, while that of the lutein was 156, 28 and 33.6 μg/100 g respectively (Boudries et al., 2007; Al Farsi and Lee, 2008). A significant decline in the carotenoid levels occurs during the transition from the khalal through tamar

Fig. 3. Structures of carotenoids present in dates.

Flavonoids present in plants possess diverse health benefits, which includes antioxidant and radical scavenging activities, reduction of certain chronic diseases, prevention of some cardiovascular disorders and certain kinds of cancerous processes (Tapas et al., 2008). Hong et al. (2006) assessed the flavonoid content in the Deglet Noor variety during the Khalal stage of maturity and identified thirteen flavonoid glycosides of luteolin, quercetin, and apigenin (Fig. 5). It was also observed that both methylated and sulfated forms of luteolin and quercetin are present as mono-, di-, and triglycosylated conjugates while apigenin is present only as the diglycoside. Quercetin and luteolin formed primarily O-glycosidic linkages whereas apigenin was present as the C-glycoside. As of today, dates also have the unique distinction of being the only food to contain flavonoid sulfates (Hong et al., 2006). Chaira et al. (2009) recently reported that among the famous Tunisian dates the highest content of flavonoids was present in the Korkobbi variety (54.46 quercetin equivalents/100 g fresh weight).

Fig. 4. Structures of procyanidins present in dates.


Fig. 5. Structures of flavanoids present in dates.

1817

fertility (Khare, 2007; Zaid, 1999). Dried dates are also of use in Ayurveda, the traditional Indian system of medicine. The fruit pulp is regarded to be antitussive, expectorant, demulcent, laxative, diuretic and restorative (Khare, 2007). Consumption of dates is believed to be strengthening for the body, to prevent premature graying of hair, wrinkle formation and to give the skin a lustrous healthy look. The date kernels have also been reported to exhibit anti-aging properties and to reduce wrinkling of skin in women (Bauza, 2002).The date pulp is boiled in milk until soft and used as a tonic especially for pregnant and lactating mothers (Puri et al., 2000). Dried fruit are pounded and mixed with almonds, quince seed, pistachio nuts, spices and sugar and the mixture, which is highly nutritious, is given to pregnant women and new mothers (Chandra et al., 1992; Puri et al., 2000). Dates are also given to infants with teething problems as are believed to harden the gums (Zaid, 1999). The consumption of date boiled with black pepper and cardamom is supposed to alleviate headaches, dry coughs, lethargy, mild fever and loss of appetite (Zaid, 1999). Chewing of dry dates every morning is supposed to increase immunity against common cold and to relieve asthma (Zaid, 1999). Regular consumption of date is beneficial in ameliorating cough, rheumatism, burning sensation, nephropathy, gastropathy, bronchitis and sexual debility (Selvam, 2008). It is demulcent, expectorant, nutrient, emetic, laxative, aphrodisiac, and is good for the heart. It is prescribed for gastroenteritis, coughs, respiratory diseases, asthma, chest complaints, fevers, high blood pressure and fatigue (Khare, 2007; Selvam, 2008).

6.6. Anthocyanins

7.2. Experimentally validated uses

Anthocyanins (Fig. 6) are water-soluble vacuolar pigments and may appear in red, purple, or blue. They are widely distributed in many fruits, vegetables, cereal grains and flowers and are of potential health benefits (Wang et al., 1997). Studies by Al Farsi et al. (2005b) have shown that among the analyzed fresh date varieties, the highest amount of anthocyanins were detected in the Khasab (1.5 mg/100 g), followed by the Fard (0.9 mg/100 g) and Khalas (0.87 mg/100 g) varieties and that a direct correlation existed between the levels of anthocyanin and the fruit color. Anthocyanins were detected only in fresh dates, indicating that they may be destroyed upon sun-drying (Al Farsi et al., 2005b).

Scientific research on the date palm was scanty until 1969. However, by the early 1970s, due to the interest of Food and Agricultural Organization and keenness of policy makers of Arabian Countries, scientific endeavors were initiated on botanical, horticultural and pharmacological aspects of date palm (Anwar, 2006). In the following sections the reported pharmacological studies are addressed under the sub titles of in vitro studies, animal studies and clinical studies, accordingly as well as in Table 2.

7. Biological and pharmacological activities of dates 7.1. Traditional medicinal applications Since antiquity, both fruits and pits of dates have been of use in the various traditional and folk systems of medicines where date palms are found to be growing (Duke, 1992; Khare, 2007). An ethnomedicinal survey conducted by Tahraoui et al. (2007) in the south-eastern Morocco has shown that dates are traditionally used to treat hypertension and diabetes (Tahraoui et al., 2007). In ancient Egypt date was used as an important ingredient in various aphrodiasiac and tonic confections. The regular consumption of date palm pollen and the male flowers was believed to be an aphrodisiac and to enhance

Fig. 6. Structures of anthocyanin present in dates.

7.2.1. In vitro studies 7.2.1.1. Antioxidant activity. In vitro studies by Vayalil (2002) for the first time have shown that the aqueous extract of date fruit was a potent scavenger of superoxide and hydroxyl radicals and to inhibit iron-induced lipid peroxidation and protein oxidation in the rat brain homogenate in a concentration-dependent manner (Vayalil, 2002). Subsequently, other investigators have confirmed these observations with different varieties of date (Abdul and Allaith, 2008; Al Farsi et al., 2005b; Mansouri et al., 2005). Recently, Chaira et al. (2009) evaluated the antioxidant activity of Tunisian date. The study showed that the Korkobbi variety possessed the best lipoperoxyl radical scavenging activity, while the Rotbi variety was very effective in scavenging the hydroxyl radicals. The Trolox equivalent antioxidant capacity value observed to be Korkobbi N Bouhattam N Baht = Smiti N Bekreri = Garn ghzal N Mermilla = Kenta N Nefzaoui = Rotbi. The authors suppose that the highest level of flavonoids in the Korkobbi variety was responsible for the highest antiradical effects (Chaira et al., 2009). Animal studies have also shown that oral feeding of p-coumaric acid present in date increases the expression of antioxidant enzyme genes in rat cardiac tissue (Yeh et al., 2008). The observed antioxidant activity of dates has, been attributed to phenolic compounds, anthocyanins, flavonoid glycosides and procyanidins present in it and that sun-drying and ripening decrease the antioxidant activity (Abdul and Allaith, 2008; Al Farsi et al., 2005b). Selenium present in dates is also reported to contribute to the antioxidant effects. Multiple studies have shown that this essential trace element exerts its antioxidant function mainly in the form of selenocysteine residues

1818


Fig. 7. Pharmacological activities of date fruit (arrow up increase and arrow up decrease).

that are an integral constituent of ROS-detoxifying selenoenzymes (GPx, thioredoxin reductases and possibly selenoprotein P (Steinbrenner and Sies, 2009) When considered in total it is very evident

that the presence of diverse phenolic compounds and selenium may have been responsible for the observed free radical scavenging and antioxidant effects (Ferguson et al., 2004).

Table 2 Effect of date fruits in exerting the various pharmacological properties in experimental systems of study.

7.2.1.2. Antimutagenic activity. Studies by Vayalil (2002) have shown that the date fruit extract possessed antimutagenic properties in the Ames mutagenicity assay. The extract caused a dose-dependent inhibition of benzo (a) pyrene-induced mutagenecity on Salmonella tester strains TA-98 and TA-100 with metabolic activation. A low concentration of 3.6 mg/plate and 4.3 mg/plate was found to cause 50% inhibition of His + revertants formation in TA-98 and TA-100, respectively (Vayalil, 2002). The date components proanthocyanidins (Dauer et al., 1998), anthocyanins (Gasiorowski et al., 1997), βcarotene (Brockman et al., 1992) and phenolic acids (Birosová et al., 2005) are all reported to possess antimutagenic effects. Dates are rich in selenium and studies have also shown that at low concentration selenium possess antimutagenic effects against diverse mutagens and carcinogens (Hocman, 1988; Lin et al., 1984; Martin et al., 1981). Cumulatively the presence of all these components in the date fruit may have been responsible for the observed antimutagenic effects in Ames test and needs validation in the animal systems of studies.

Pharmacological property In vitro studies 1. Antioxidant activity

2. Antimutagenic activity 3. Antiheamolytic activity 4. Antiviral activity

5. Antifungal activity

Animal studies 1. Anti-inflammatory activity

2. Action on gastrointestinal tract 3. Antihyperlipidemic activity 4. Hepatoprotective activity

5. Nephroprotective activity 6. Anticancer activity 7. Immunostimulant activity 8. Gonadotropic activity

Observation and references

Scavenges free radical, inhibit iron-induced lipid peroxidation and protein oxidation (Vayalil, 2002; Al Farsi et al., 2005b; Mansouri et al., 2005; Abdul and Allaith, 2008; Chaira et al., 2009). Inhibits benzo (a) pyrene-induced mutagenecity in the Ames test (Vayalil, 2002). Inhibits haemolytic activity of streptolysin O (Abuharfeil et al., 1999). Prevent lytic activity of Pseudomonas phage ATCC 14209-B1 on Pseudomonas aeroginosa (Jassim and Naji, 2008). Antifungal activity against Candida albicans and C. krusei (Shraideh et al., 1998).

Increase plasma antioxidant (Vitamin C, E, A, βcarotene) levels and decrease lipid peroxides. Reduce swelling, ESR and plasma fibrinogen (Doha and Al-Okbi, 2004). Increase gastrointestinal transit time, reduces ethanolinduced gastric ulceration (Al Qarawi et al., 2003, 2005). Reduce plasma triglycerides, total and LDL cholesterol (Salah and Al-Maiman, 2005; El-Mougy et al., 1991). Prevent dimethoate-induced hepatotoxicity—decrease hepatic markers (ALT, AST, alkaline phosphatase, GGT and LDH), decrease vacuolization, necrosis, congestion, inflammation and enlargement of sinusoids. Has protective effect against CCl4 induced hepatotoxicity (Saafi et al., 2010; Al Qarawi et al., 2004). Prevents gentamicin-induced renal damage and reduce levels of creatinine and urea (Al Qarawi et al., 2008). Regression of Sarcoma-180 tumour in mice (Ishurda and John, 2005). Enhance both cell mediated and humoral immunity (Puri et al., 2000). Increase FSH, LH, testosterone, oestrogen—increase spermatogenesis, sperm count, growth (El-Mougy et al., 1991; Elgasim et al., 1995; Ali et al., 1999).

7.2.1.3. Effect on hemolytic activity of Streptococcus pyogenes. In vitro studies have shown that date extract effectively slowed the growth of S. pyogenes. Incubation of the bacteria for 24 h with date fruit extract at 5, 10 and 20% dilution caused a 30.8%, 64.7% and 88.5% decrease in the microbial number when compared with the concurrent (date extract free medium) cohorts. Further at low concentrations the date extract neutralized the hemolytic activity of the streptococcal exotoxin, streptolysin O, probably due to erythrocyte membrane stabilization and inhibition of streptolysin O enzyme. Fractionated studies showed that the inhibitory substance was steroidal in nature and not proteinaceous as deproteinization of the extract did not decrease its inhibitory effect (Abuharfeil et al., 1999). Independent investigations have shown that the anthocyanins, carotenoids, procyanidins and flavonoids present in dates are known to possess membrane protective effects (Hocman, 1988; Tapas et al., 2008) and it is quite possible that these compounds may have protected the erythrocyte membrane from damage. 7.2.1.4. Antiviral activity. The crude acetone extract of the pit of date fruit (Phoenix dactylifera L.) was evaluated for its antiviral activity


against lytic Pseudomonas phage ATCC 14209-B1, using Pseudomonas aeruginosa ATCC 25668 as the host cell (Jassim and Naji, 2008). The date pit extract inhibited the infectivity of Pseudomonas phage ATCC 14209-B1 and completely prevented bacterial lysis. The antiviral activity of date pits was found to be mediated by binding to the phage, with minimum inhibitory concentration of b10 mg/ml (Jassim and Naji, 2008). In milieu of these observations antiviral studies should be extended to other viruses important to humans. 7.2.1.5. Antifungal activity. Shraideh et al. (1998) reported that treatment of Candida albicans with the extract of Barhi date caused distortion, weakening and partial collapse of the cell wall. At high concentrations drastic damage in the form of cell lysis, leakage of cytoplasmic material and eventual cell death was observed. In total these results suggest that the date extract phytochemicals may have multiple effects on Candida and with further studies may be of therapeutic uses. In vitro studies have shown that flavonoids possess antifungal activities against C. albicans and C. krusei, and that their presence in the extract may have been responsible for the observed antifungal effects (Orhan et al., 2009; Ozçelik et al., 2006). 7.2.2. Animal studies 7.2.2.1. Anti-inflammatory properties. Excess generation of free radicals generated from activated inflammatory leukocytes, especially under conditions of chronic inflammation is highly deleterious and aggravates arthritis, diabetes, etc. Therefore, for better health and vitality their control is extremely important. Studies have shown that both methanolic and aqueous extract of date fruit pulp and the methanolic extract of date seeds possess anti-inflammatory activity in the rat adjuvant arthritis model in rats. The extracts increased the plasma antioxidant state (vitamin C, E, A and β-carotene) levels and decreased the levels of lipid peroxides. Of all the extracts the methanolic extract of the pulp was most effective in reducing the foot swelling, ESR and plasma fibrinogen. The extracts increased the body weight gain and food efficiency ratio suggesting its benefit. Acute toxicity studies with mice showed that the methanolic extract and aqueous extract of the pulp were safe up to 6 g/kg, while the LD50 for the methanolic extract of the seed was 6.75 g/kg (Doha and AlOkbi, 2004). Innumerable studies have shown that the date constituents proanthocyanidin (Subarnas and Wagner, 2000), flavonoids (Robak and Gryglewski, 1996), polyphenols (Gescher, 2004), βcarotene (Uteshev et al., 2000), and the mineral selenium (Roberts, 1963) possess anti-inflammatory effects in different models of study and may have contributed for the beneficial effects. 7.2.2.2. Gastrointestinal protective activity. Dates are anecdotally reputed to be useful against peptic ulcers, and the fact that Muslims customarily consume more of dates during the fasting month of Ramadan, could be possibly to protect the gastric mucosa from the damaging effects of the gastric acid (Al Qarawi et al., 2005). Feeding rats with aqueous and ethanolic undialyzed extracts of dates and date pits have been observed to cause a concentration-dependent increase in gastrointestinal transit time. These observations lend credence to the ethnomedicinal claim that dates may be useful to humans with gastric ulcers and also as a natural laxative (Al Qarawi et al., 2003). The aqueous and ethanolic extracts of date fruits were observed to be effective in ameliorating the ethanol-induced gastric ulceration in rats. The gastroprotective activity is postulated to be multi-factorial and may include antioxidant action (Al Qarawi et al., 2005). The Date constituents proanthocyanidin (Iwasaki et al., 2004), flavonoids (Mota et al., 2009), cyanidin 3-glucoside (Li et al., 2008), β-carotene (Garamszegi et al., 1989), β-sitosterol (Xiao et al., 1992) and selenium (Parmar et al., 1988) possess gastroprotective effects against different ulcerogens and this may have contributed to the observed effects.

1819

7.2.2.3. Antihyperlipidemic activity. Coronary heart disease is strongly related to decrease in the concentrations of high density lipoprotein cholesterol and increase in the low density lipoprotein cholesterol. Salah and Al-Maiman (2005) have reported that feeding the defatted date seed flour containing diet at 1.5%, 2.5% and 5.2% to rats reduced the plasma triglycerides, total cholesterol and low density lipoprotein (Salah and Al-Maiman, 2005). Similar observations have also been observed when date seed fibers (2.5%) were fed to rats (El-Mougy et al., 1991). Preclinical studies have shown that the phytochemicals caffeic acid (Lafay et al., 2005), β-sitosterol (Wong, 2001), proanthocyanidin (Bagchi et al., 2003), catechin (Auger et al., 2005), quercetin (Auger et al., 2005; Kamada et al., 2005), anthocyanins (Finné Nielsen et al., 2005) and selenium present possess cardioprotective and antihyperlipidemic effects in various animal models of study and contributed to the observed effects (Dhingra and Bansal, 2005, 2006; Kaur and Bansal, 2009). 7.2.2.4. Hepatoprotective activity. Liver diseases remain one of the serious health problems and no satisfactory protective drugs are available. Recently, Saafi et al. (2010) have also reported that date fruit extract protected rats against dimethoate-induced hepatotoxicity. When compared to the dimethoate alone treated controls, treatment of rats with date extract decreased the levels of the hepatic markers enzymes (transaminases, alkaline phosphatase, gammaglutamyl transferase and lactate dehydrogenase), hepatic levels of malondialdehyde and concomitantly increased the levels of antioxidant enzymes (Saafi et al., 2010). The histopathological observations were in congruence to the biochemical observations and a decrease in the level of vacuolization, necrosis, congestion, inflammation and enlargement of sinusoids were observed (Saafi et al., 2010). Studies have shown that feeding rats with the aqueous extract of date flesh or pits significantly reduced CCl4-induced elevation in plasma enzyme and bilirubin concentration. The histopathological studies confirmed the biochemical observations that date extract possess hepatoprotective effects. (Al Qarawi et al., 2004). Studies have confirmed that selenium (Hafeman and Hoekstra, 1977); anthocyanin (Obi et al., 1998), ferulic acid (Srinivasan et al., 2005), caffeic acid (Añón et al., 1992; Janbaz et al., 2005) and quercetin (Janbaz et al., 2005), chlorogenic acids (Añón et al., 1992), β-carotene (Seifert et al., 1995), proanthocyanidins (Ipatova et al., 2003), apigenin (Zheng et al., 2005) and luteolin (Domitrović et al., 2008), the date constituents have all been reported to possess hepatoprotective effects against the CCl4-induced hepatic damage in rodents. It is logical to assume that the presence of these compounds may have contributed for the hepatoprotective effects of the date extract. 7.2.2.5. Nephroprotective activity. Nephrotoxicity is a common side effect of pharmacological agents (like analgesics, antibiotics, cytostatics and other drugs) and its prevention or amelioration is important. Al Qarawi et al. (2008) investigated the renoprotective effect of date fruit extract on gentamicin-induced nephrotoxicity in rats. Gentamicin treatment significantly increased the plasma concentrations of creatinine and urea and induced a marked necrosis of the renal proximal tubules. Feeding of date flesh and pit extract reduced the levels of plasma creatinine and urea concentrations and ameliorated gentamicin-induced damage to the proximal tubular regions of the rat kidneys (Al Qarawi et al., 2008). Previous studies have shown that selenium (Ademuyiwa et al., 1990) and quercetin (Abdel-Raheem et al., 2009) possess protective effects against the gentamicin-induced nephrotoxicity in rats and that they may have been responsible for the beneficial effects. 7.2.2.6. Anticancer activity. Studies by Ishurda and John (2005) for the first time have shown that the glucans prepared from the date fruits possess antineoplastic effects in experimental system of study. The authors observed a dose dependant anticancer activity with an

1820


optimum activity at a dose of 1 mg/kg in mice bearing Sarcoma-180 solid tumors. The authors hypothesize that the observed antitumor activity could be correlated to their (1 → 3)-β-d-glucan linkages (Ishurda and John, 2005). To corroborate these observations studies by Fullerton et al. (2000) have shown that the β-glucan, isolated from the Maitake mushroom also exerted antineoplastic effects on the cultured metastatic prostatic cancer cells (PC-3) in vitro. Treatment with the β-glucan containing media caused a dose-dependent increase in apoptosis, which concomitantly decreased the cell viability of the PC-3 cells in vitro (Fullerton et al., 2000). A similar mechanism of action may have very well initiated for the observed tumor regression of the Sarcoma-180 when administered with the glucans isolated from the dates. 7.2.2.7. Immunostimulatory activity. Immune activation is an effective as well as protective approach against infectious diseases. Immunostimulants enhance the overall immunity of the host, and present a nonspecific immune response against the microbial pathogens. They also work to heighten humoral and cellular mediated immune responses, by either enhancing cytokine secretion, or by directly stimulating B- or Tlymphocytes (Puri et al., 2000). Ingestion of phytochemicals to support the immune system or to combat infections has been a long standing traditional practice. Feeding of ethanol extract of dry dates to parturated mice enhanced both cell mediated and humoral immunity (Puri et al., 2000). Experimental studies have shown that selenium (Sheffy and Schultz, 1979), carotenoids (Chew, 1993), quercetin (Akbay et al., 2003), kaempherol (Akbay et al., 2003) and isorhamnetin (Akbay et al., 2003) possess immunostimulatory effects and may be responsible for the observed effects. 7.2.2.8. Gonadotropic activity. Dates have been used as an important ingredient in various aphrodisiacs and tonic confections in the various traditional medicines and scientific studies have validated this. Date extracts have been shown to increase sperm count in guinea pigs and to enhance spermatogenesis and increase the concentration of testosterone, follicle stimulating hormone, and luteinizing hormone in rats (El-Mougy et al., 1991). Incorporation of date pits in the animal feed is also observed to enhance growth and this was ascribed to an increase in the plasma level of estrogens (Elgasim et al., 1995) or testosterone (Ali et al., 1999). The date phytochemicals genistein (Eustache et al., 2009; Roberts et al., 2000), vitamin A (Bartlett et al., 1989) and selenium (Jana et al., 2008) have all been reported to protected testicular functions against various stress and possess gonadotropic activity, and their presence compounds may have contributed to the observed effects. 7.2.3. Clinical Studies Recently, Rock et al. (2009) studied the effect of two varieties of dates (Medjool and Hallawi) on serum oxidative status, glucose and lipid levels in healthy human subjects. The volunteers were advised to consume 100 g/day of either variety of dates for a period of 4 weeks, after which they were tested for variations in the mentioned serum parameters. A significant decrease in the levels of triacylglycerol was observed, possibly due to the high dietary fiber content in dates. Although an increase in the serum glucose level concentrations on postprandial samples was observed, the fasting serum glucose levels remained unaltered. The decreased serum triacylglycerol levels and oxidative stress during the month of date consumption was suggested to be the reason for the significantly unaffected serum cholesterol levels. The presence of a variety of phenolic compounds especially the ferulic acid and coumaric acid derivatives may have been responsible for the observed free radical scavenging effects. The Hallawi date consumption showed a decrease in basal serum oxidative stress and the susceptibility of serum to AAPH [2, 2′-azobis (2-amidinopropane) hydrochloride]-induced lipid peroxidation. The presence of higher phenolic concentration, catechins (antioxidants) as well as the

different absorption, metabolism and bioactivity of the various phenolic compounds in Hallavi dates, attributes to the increased antioxidant property, higher FRAP as well as serum high density lipoprotein-associated PON1 activity as compared to the Medjool variety. These results justifies the various in vitro studies; showing that dates in general and the Hallawi variety in particular are beneficial and can be included in our regular diet, without having to worry on its adverse affects (Rock et al., 2009). 8. Conclusion The information accrued in the past four decades suggest that dates possess diverse medicinal uses including antihyperlipidemic, anticancer, gastroprotective, hepatoprotective and nephroprotective activities (Fig. 7) and thereby serving as an important healthy food in the human diet. The observed pharmacological properties may be attributed to the presence of a high concentration of minerals and various other phytochemicals of diverse chemical structure. The presence of compounds such as phenolics with a potential to scavenge free radicals, increase antimutagenic effects and to stimulate the immune system may contribute towards the various pharmacological effects. Dates also contain vitamins (A, B1, B2, B3, B6, B9 and C) which are essential for carbohydrates, fat, protein metabolism, synthesis of DNA and as an antioxidant to protect tissues from oxidative stress. The presences of insoluble fibers like cellulose, hemicelluloses, pectin, and lignin which are present in the date flesh are important for the health of the digestive tract especially in reducing the risk of bowel cancer, and diverticular disease as well as in improving the cardiac vitality. Dates are rich sources of selenium, copper, potassium, and magnesium and moderate of manganese, iron, phosphorus and calcium; and their regular consumption are reported to provide the required RDA/AI at least in part. The high potassium and low sodium contents in dates are desirable for people suffering from hypertension. On an average dates contain 0.8 μg Se, which is nearly 5.6 fold more than the RDA/AI. Selenium is an oligoelement with essential biological functions and its presence may have partly been responsible for the myriad beneficial effects. While all pharmacological studies have been with rodents and validated dates clinical applicability; in vitro studies with relevant assays will help in understanding the mode of action responsible for the various pharmacological properties. The required information when available will enhance our knowledge and appreciation for the use of dates in our daily diet. Due to its abundance and low cost, dates remain a species with tremendous potential and countless possibilities for further investigation. Considering the fact that dates are relatively cheap, nutritious and is devoid of toxic effects it is safe to suggest that their consumption should be recommended on a daily basis for better health, vitality and vigor. Acknowledgments The authors MSB, BRVB are grateful to Rev. Fr. Patrick Rodrigus (Director), Rev. Fr. Denis D'Sa (Administrator) and Dr. Sanjeev Rai (Chief of Medical Services) and Dr. Jai Prakash Alva (Dean), of Father Muller Charitable Institutions for their unstinted support. MSB and HPB are also grateful to Prof. TL Shantha, director and Prof MB Nagaveni, Maharani Lakshmi Ammani Women's College, for their help and support. References Abdelhak, M., Guendez, E., Eugene, K., & Kefalas, P. (2005). Phenolic profile and antioxidant activity of the Algerian ripe date palm fruit (Phoenix dactylifera). Food Chemistry, 89, 411−420.

M.S. Baliga et al. / Food Research International 44 (2011) 1812–1822 Abdel-Raheem, I. T., Abdel-Ghany, A. A., & Mohamed, G. A. (2009). Protective effect of quercetin against gentamicin-induced nephrotoxicity in rats. Biological & Pharmaceutical Bulletin, 32, 61−67. Abdul, A., & Allaith, A. (2008). Antioxidant activity of Bahraini date palm (Phoenix dactylifera L.) fruit of various cultivars. International Journal of Food Science and Technology, 43, 1033−1040. Abuharfeil, N. M., Saeb El, S., Yousef, M., & Abdul-Karim, J. S. (1999). Effect of date fruits, Phoenix dactyliferia L., on the hemolytic activity of Streptolysin O. Pharmaceutical Biology, 37, 335−339. Ademuyiwa, O., Ngaha, E. O., & Ubah, F. O. (1990). Vitamin E and selenium in gentamicin nephrotoxicity. Human and Experimental Toxicology, 9, 281−288. Ahmed, A. I., Ahmed, A. W. K., & Robinson, R. K. (1995). Chemical composition of date varieties as influenced by the stage of ripening. Food Chemistry, 54, 305−309. Akbay, P., Basaran, A. A., Undeger, U., & Basaran, N. (2003). In vitro immunomodulatory activity of flavonoid glycosides from Urtica dioica L.. Phytotherapy Research, 17, 34−37. Al Farsi, M., Alasalvar, C., Morris, A., Baron, M., & Shahidi, F. (2005a). Comparison of antioxidant activity, anthocyanins, carotenoids, and phenolics of three native fresh and sun-dried date (Phoenix dactylifera L.) varieties grown in Oman. Journal of Agricultural and Food Chemistry, 53, 7592−7599. Al Farsi, M., Alasalvar, C., Morris, A., Baron, M., & Shahidi, F. (2005b). Compositional and sensory characteristics of three native sun-dried date (Phoenix dactylifera L.) varieties grown in Oman. Journal of Agricultural and Food Chemistry, 53, 7586−7591. Al Farsi, M. A., & Lee, C. Y. (2008). Nutritional and functional properties of dates: a review. Critical Reviews in Food Science and Nutrition, 48, 877−887. Al Noimi, J., & Al-Amir, G. (1980). Physiology and morphology of date palm. Al-Basra University, Iraq: Faculty of Agriculture. Al Qarawi, A. A., Abdel-Rahman, H., Ali, B. H., Mousa, H. M., & El-Mougy, S. A. (2004). Protective effect of extracts from dates (Phoenix dactylifera L.) on carbon tetrachloride-induced hepatotoxicity in rats. The International Journal of Applied Research in Veterinary Medicine, 3, 176−180. Al Qarawi, A. A., Abdel-Rahman, H., Ali, B. H., Mousa, H. M., & El-Mougy, S. A. (2005). The ameliorative effect of dates (Phoenix dactylifera L.) on ethanol-induced gastric ulcer in rats. Journal of Ethnopharmacology, 98, 313−317. Al Qarawi, A. A., Abdel-Rahman, H., Mousa, H. M., Ali, B. H., & El-Mougy, S. A. (2008). Nephroprotective Action of Phoenix dactylifera in gentamicin-induced nephrotoxicity. Pharmaceutical Biology, 46, 227−230. Al Qarawi, A. A., Ali, B. H., Al-Mougy, S. A., & Mousa, H. M. (2003). Gastrointestinal transit in mice treated with various extracts of date (Phoenix dactylifera L.). Food Chemical Toxicology, 41, 37−39. Ali Mohamed, A. Y., & Khamis, A. S. (2004). Mineral ion content of the seeds of six cultivars of Bahraini date palm (Phoenix dactylifera). Journal of Agricultural and Food Chemistry, 52, 6522−6525. Ali, B. H., Bashir, A. K., & Al Hadrami, G. (1999). Reproductive hormonal status of rats treated with date pits. Food Chemistry, 66, 437−441. Al-Shahib, W., & Marshall, R. J. (2003). The fruit of the date palm: Its possible use as the best food for the future. International Journal of Food Science and Nutrition, 54, 247−259. Añón, M. T., Ubeda, A., & Alcaraz, M. J. (1992). Protective effects of phenolic compounds on CCl4-induced toxicity in isolated rat hepatocytes. Zeitschrift für Naturforschung. C. Journal of biosciences, 47, 275−279. Anwar, M. A. (2006). Phoenix dactylifera l: a bibliometric study of the Literature on date palm. Malaysian Journal of library and Information Science, 11, 41−60. Auger, C., Teissedre, P. L., Gérain, P., Lequeux, N., Bornet, A., Serisier, S., Besançon, P., Caporiccio, B., Cristol, J. P., & Rouanet, J. M. (2005). Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. Journal of Agricultural and Food Chemistry, 53, 2015−2021. Bagchi, D., Sen, C. K., Ray, S. D., Das, D. K., Bagchi, M., Preuss, H. G., & Vinson, J. A. (2003). Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutation Research, 523–524, 87−97. Bartlett, J. M., Weinbauer, G. F., & Nieschlag, E. (1989). Quantitative analysis of germ cell numbers and relation to intratesticular testosterone following vitamin A-induced synchronization of spermatogenesis in the rat. The Journal of Endocrinology, 123, 403−412. Bauza, E. (2002). Date palm kernel extract exhibits antiaging properties and significantly reduces skin wrinkles. International Journal of Tissue Reactions, 24, 131−136. Birosová, L., Mikulásová, M., & Vaverková, S. (2005). Antimutagenic effect of phenolic acids. Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, 149, 489−491. Boudries, H., Kefalas, P., & Hornero-Méndez, D. (2007). Carotenoid composition of Algerian date varieties (Phoenix dactylifera) at different edible maturation stages. Food Chemistry, 101, 1372−1377. Brockman, H. E., Stack, H. F., & Waters, M. D. (1992). Antimutagenicity profiles of some natural substances. Mutation Research, 267, 157−172. Chaira, N., Smaali, M. I., Martinez-Tomé, M., Mrabet, A., Murcia, M. A., & Ferchichi, A. (2009). Simple phenolic composition, flavonoid contents and antioxidant capacities in water–methanol extracts of Tunisian common date cultivars (Phoenix dactylifera L.). Internaltional Journal of Food Sciences and Nutrition, 60, 316−329. Chandra, A., Chandra, A., & Gupta, I. C. (1992). Date palm research in Thar Desert. Jodhpur (India): Scientific Publishers. Chew, B. P. (1993). Role of carotenoids in the immune response. Journal of Dairy Science, 76, 2804−2811. Dauer, A., Metzner, P., & Schimmer, O. (1998). Proanthocyanidins from the bark of Hamamelis virginiana exhibit antimutagenic properties against nitroaromatic compounds. Planta Medica, 64, 324−327.

1821

Dhingra, S., & Bansal, M. P. (2005). Hypercholesterolemia and apolipoprotein B expression: regulation by selenium status. Lipids in Health and Disease, 5(4), 28. Dhingra, S., & Bansal, M. P. (2006). Modulation of hypercholesterolemia-induced alterations in apolipoprotein B and HMG-CoA reductase expression by selenium supplementation. Chemico-biological Interactions, 161, 49−56. Di Mascio, P., Murphy, M. E., & Sies, H. (1991). Antioxidant defense systems: the role of carotenoids, tocopherols, and thiols. The American Journal of Clinical Nutrition, 53, 194S−200S. Doha, M. A., & Al-Okbi, S. Y. (2004). In vivo evaluation of antioxidant and antiinflammatory activity of different extracts of date fruits in adjuvant arthritis. Polish Journal of Food and Nutrition Sciences, 13, 397−402. Domitrović, R., Jakovac, H., Grebić, D., Milin, C., & Radosević-Stasić, B. (2008). Dose- and time-dependent effects of luteolin on liver metallothioneins and metals in carbon tetrachloride-induced hepatotoxicity in mice. Biological Trace Element Research, 126, 176−185. Dowson, V. H. W. (1982). Date Production and Protection. FAO Plant Production and Protection Paper No. 35. Food and Agriculture Organization of the United Nations. Rome. Duke, J. A. (1992). Handbook of phytochemicals of GRAS herbs and other economic plants. Boca Raton, FL, USA: CRC Press. Elgasim, E. A., Alyousif, Y. A., & Homeida, A. M. (1995). Possible hormonal activity of date pits and flesh fed to meat animals. Food Chemistry, 52, 149−150. El-Mougy, S. A., Abdel-Aziz, S. A., Al-Shanawany, M., & Omar, A. (1991). The gonadotropic activity of Palmae in mature male rats. Alexandria Journal of Pharmaceutical Sciences, 5, 156−159. Eustache, F., Mondon, F., Canivenc-Lavier, M. C., Lesaffre, C., Fulla, Y., Berges, R., Cravedi, J. P., Vaiman, D., & Auger, J. (2009). Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility. Environmental Health Perspectives, 117, 1272−1279. Fadel, M. A., Kurmestegy, L., Rashed, M., & Rashed, Z. (2006). Fruit color properties of different cultivars of dates (Phoenix dactylifera, L.).Agricultural Engineering International: the CIGR E journal, VIII (Manuscript FP 05 005). Fayadh, J. M., & Al-Showiman, S. S. (1990). Chemical composition of date palm (Phoenix dactylifera L.). Journal of the Chemical Society of Pakistan, 12, 84−103. Ferguson, L. R., Philpott, M., & Karunasinghe, N. (2004). Dietary cancer and prevention using antimutagens. Toxicology, 198, 147−159. Fine, A. M. (2000). Oligomeric proanthocyanidin complexes: history, structure, and phytopharmaceutical applications. Alternative Medicine Review: A Journal of Clinical Therapeutic, 5, 144−151. Finné Nielsen, I. L., Elbøl Rasmussen, S., Mortensen, A., Ravn-Haren, G., Ma, H. P., Knuthsen, P., Hansen, B. F., McPhail, D., Freese, R., Breinholt, V., Frandsen, H., & Dragsted, L. O. (2005). Anthocyanins increase low-density lipoprotein and plasma cholesterol and do not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits. Molecular Nutrition & Food Research, 49, 301−308. Fullerton, S. A., Samadi, A. A., Tortorelis, D. G., Choudhury, M. S., Mallouh, C., Tazaki, H., & Konno, S. (2000). Induction of apoptosis in human prostatic cancer cells with betaglucan (Maitake mushroom polysaccharide. Molecular Urology, 4, 7−13. Garamszegi, M., Jávor, T., Sütö, G., Vincze, A., Tóth, G., & Mózsik, G. (1989). Effect of atropine, PGF2 alpha and cimetidine on the beta-carotene induced cytoprotection in ethanol-treated rats. Acta Physiologica Hungarica, 73, 221−224. Gasiorowski, K., Szyba, K., Brokos, B., Kołaczyńska, B., Jankowiak-Włodarczyk, M., & Oszmiański, J. (1997). Antimutagenic activity of anthocyanins isolated from Aronia melanocarpa fruits. Cancer Letters, 28, 37−46. Gescher, A. (2004). Polyphenolic phytochemicals versus non-steroidal anti-inflammatory drugs: which are better cancer chemopreventive agents? Journal of Chemotherapy, 16, 3−6. Habib, H. M., & Ibrahim, W. H. (2009). Nutritional quality evaluation of eighteen date pit varieties. International Journal of Food Sciences and Nutrition, 60, 99−111. Hafeman, D. G., & Hoekstra, W. G. (1977). Protection against carbon tetrachlorideinduced lipid peroxidation in the rat by dietary vitamin E, selenium, and methionine as measured by ethane evolution. The Journal of Nutrition, 107, 656−665. Hocman, G. (1988). Chemoprevention of cancer: selenium. The International Journal of Biochemistry, 20, 123−132. Hong, Y. J., Tomas-Barberan, F. A., Kader, A. A., & Mitchell, A. E. (2006). The flavonoid glycosides and procyanidin composition of Deglet Noor dates (Phoenix dactylifera). Journal of Agricultural and Food Chemistry, 54, 2405−2411. Hulme, A. C. (1970). The biochemistry of fruits and their products, Vol 1, London and New York: Academic Press. Ipatova, O. M., Prozorovskaia, N. N., Rusina, I. F., & Prozorovskiĭ, V. N. (2003). Antioxidant properties of a leaf extract from Aronia (Aronia melanocarba) containing proanthocyanidins. Biomeditsinskaia Khimiia, 49, 165−176. Ishurda, O., & John, F. K. (2005). The anti-cancer activity of polysaccharide prepared from Libyan dates (Phoenix dactylifera L.). Carbohydrate Polymers, 59, 531−535. Iwasaki, Y., Matsui, T., & Arakawa, Y. (2004). The protective and hormonal effects of proanthocyanidin against gastric mucosal injury in Wistar rats. Journal of Gastroenterology, 39, 831−837. Jana, K., Samanta, P. K., Manna, I., Ghosh, P., Singh, N., Khetan, R. P., & Ray, B. R. (2008). Protective effect of sodium selenite and zinc sulfate on intensive swimminginduced testicular gamatogenic and steroidogenic disorders in mature male rats. Applied Physiology, Nutrition, and Metabolism, 33, 903−914. Janbaz, K. H., Saeed, S. A., & Gilani, A. H. (2005). Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. Phytomedicine, 11, 424−430. Jassim, S. A. A., & Naji, M. A. (2008). In vitro evaluation of the antiviral activity of an extract of date palm (Phoenix dactylifera L.) pits on a pseudomonas phage. Evidencebased complementary and alternative medicine, 15, 1−6.

1822


Kamada, C., Da Silva, E. L., Ohnishi-Kameyama, M., Moon, J. H., & Terao, J. (2005). Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high cholesterol-fed rabbit. Free Radical Research, 39, 185−194. Kaur, H. D., & Bansal, M. P. (2009). Studies on HDL associated enzymes under experimental hypercholesterolemia: possible modulation on selenium supplementation. Lipids in Health and Disease, 16(8), 55. Khare, C. P. (2007). Indian medicinal plants: An illustrated dictionary. : Springer Reference. Kikuchi, N., & Miki, T. (1978). The separation of date (Phoenix dactylifera) sterols by liquid chromatography. Mikrochimica Acta, 69, 89−96. Lafay, S., Gueux, E., Rayssiguier, Y., Mazur, A., Rémésy, C., & Scalbert, A. (2005). Caffeic acid inhibits oxidative stress and reduces hypercholesterolemia induced by iron overload in rats. International Journal for Vitamin and Nutrition Research, 75, 119−125. Li, C. Y., Xu, H. D., Zhao, B. T., Chang, H. I., & Rhee, H. I. (2008). Gastroprotective effect of cyanidin 3-glucoside on ethanol-induced gastric lesions in rats. Alcohol, 42, 683−687. Lin, W. S., Scrimshaw, C., & Kapoor, M. (1984). Selenium suppresses the metabolism of benzo[a]pyrene by rat-liver extracts, and exerts a dual effect on its mutagenicity. Xenobiotica, 14, 893−902. Liolios, C. C., Sotiroudis, G. T., & Chinou, I. (2008). Fatty acids, sterols, phenols and antioxidant activity of Phoenix theophrasti fruits growing in Crete, Greece. Plant Foods for Human Nutrition, 64, 52−61. Mansouri, A., Embarek, G., Kokkalouc, E., & Kefalas, P. (2005). Phenolic profile and antioxidant activity of the Algerian ripe date palm fruit (Phoenix dactylifera). Food Chemistry, 89, 411−420. Martin, S. E., Adams, G. H., Schillaci, M., & Milner, J. A. (1981). Antimutagenic effect of selenium on acridine orange and 7, 12-dimethylbenz[alpha]anthracene in the Ames Salmonella/microsomal system. Mutation Research, 82, 41−46. Mota, K. S., Dias, G. E., Pinto, M. E., Luiz-Ferreira, A., Souza-Brito, A. R., Hiruma-Lima, C. A., Barbosa-Filho, J. M., & Batista, L. M. (2009). Flavonoids with gastroprotective activity. Molecules, 14, 979−1012. Obi, F. O., Usenu, I. A., & Osayande, J. O. (1998). Prevention of carbon tetrachlorideinduced hepatotoxicity in the rat by H. rosasinensis anthocyanin extract administered in ethanol. Toxicology, 131, 93−98. Orhan, D. D., Ozçelik, B., Ozgen, S., & Ergun, F. (2009). Antibacterial, antifungal, and antiviral activities of some flavonoids. Microbiological Research. Ozçelik, B., Orhan, I., & Toker, G. (2006). Antiviral and antimicrobial assessment of some selected flavonoids. Zeitschrift fur Naturforschung. C, Journal of Biosciences, 61, 632−638. Parmar, N. S., Tariq, M., & Ageel, A. M. (1988). Gastric anti-ulcer and cytoprotective effect of selenium in rats. Toxicology and Applied Pharmacology, 92, 122−130. Puri, A., Sahai, R., Singh, K. L., Saxena, R. P., Tandon, J. S., & Saxena, K. C. (2000). Immunostimulant activity of dry fruits and plant materials used in Indian traditional medical system for mothers after childbirth and invalids. Journal of Ethnopharmacology, 71, 89−92. Robak, J., & Gryglewski, R. J. (1996). Bioactivity of flavonoids. Polish Journal of Pharmacology, 48, 555−564. Roberts, M. E. (1963). Antiinflammation studies. II. Antiinflammatory properties of selenium. Toxicology and Applied Pharmacology, 5, 500−506. Roberts, D., Veeramachaneni, D. N., Schlaff, W. D., & Awoniyi, C. A. (2000). Effects of chronic dietary exposure to genistein, a phytoestrogen, during various stages of development on reproductive hormones and spermatogenesis in rats. Endocrine, 13, 281−286. Rock, W., Rosenblat, M., Borochov-Neori, H., Volkova, N., Judeinstein, S., Elias, M., & Aviram, M. (2009). Effects of date (Phoenix dactylifera L., Medjool or Hallawi

Variety) consumption by healthy subjects on serum glucose and lipid levels and on serum oxidative status: a pilot study. Journal of Agricultural and Food Chemistry, 57, 8010−8017. Saafi, E. B., Louedi, M., Elfeki, A., Zakhama, A., Najjar, M. F., Hammami, M., & Achour, L. (2010). Protective effect of date palm fruit extract (Phoenix dactylifera L.) on dimethoate induced-oxidative stress in rat liver.Experimental and Toxicologic Pathology (Electronic publication ahead of print). Salah, A., & Al-Maiman (2005). Effect of date palm (Phoenix dactylifera) seed fibers on plasma lipids in rats. Journal of King Saud University, 17, 117−123. Seifert, W. F., Bosma, A., Hendriks, H. F., van Leeuwen, R. E., van Thiel-de Ruiter, G. C., Seifert-Bock, I., Knook, D. L., & Brouwer, A. (1995). Beta-carotene (provitamin A) decreases the severity of CCl4-induced hepatic inflammation and fibrosis in rats. Liver, 15, 1−8. Selvam, A. B. D. (2008). Inventory of vegetable crude drug samples housed in botanical survey of India, Howrah. Pharmacognosy Reviews, 2, 61−94. Sheffy, B. E., & Schultz, R. D. (1979). Influence of vitamin E and selenium on immune response mechanisms. Federatioin Proceedings, 38, 2139−2143. Shraideh, Z. A., Khaled, H., Abu-Elteen, & Sallal, A. K. J. (1998). Ultrastructural effects of date extract on Candida albicans. Mycopathologia, 142, 119−123. Srinivasan, M., Rukkumani, R., Ram Sudheer, A., & Menon, V. P. (2005). Ferulic acid, a natural protector against carbon tetrachloride-induced toxicity. Fundamental & Clinical Pharmacology, 19, 491−496. Steinbrenner, H., & Sies, H. (2009). Protection against reactive oxygen species by selenoproteins. Biochimica et Biophysica Acta, 1790, 1478−1485. Subarnas, A., & Wagner, H. (2000). Analgesic and anti-inflammatory activity of the proanthocyanidin shellegueain A from Polypodium feei METT. Phytomedicine, 7, 401−405. Tahraoui, A., El-Hilaly, J., Israili, Z. H., & Lyoussi, B. (2007). Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in southeastern Morocco (Errachidia province). Journal of Ethnopharmacology, 110, 105−117. Tapas, A. R., Sakarkar, A. M., & Kakde, R. B. (2008). Flavonoids as nutraceuticals: A review. Tropical Journal of Pharmaceutical Research, 7, 1089−1099. Uteshev, D. B., Kostriukov, E. B., Karabinenko, A. A., Kovaleva, V. L., Makarova, O. V., & Storozhakov, G. I. (2000). The anti-inflammatory activity of intal and beta-carotene in a model of experimental granulomatous lung inflammation. Patologicheskaia fiziologiia i èksperimental'naia terapiia, 2, 19−22. Vayalil, P. K. (2002). Antioxidant and antimutagenic properties of aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae). Journal of Agricultural and Food Chemistry, 50, 610−617. Wang, H., Cao, G., & Prior, R. (1997). Oxygen radical absorbing capacity of anthocyanins. Journal of Agricultural and Food Chemistry, 45, 304−309. Wong, N. C. (2001). The beneficial effects of plant sterols on serum cholesterol. The Canadian Journal of Cardiology, 17, 715−721. Xiao, M., Yang, Z., Jiu, M., You, J., & Xiao, R. (1992). The antigastroulcerative activity of beta-sitosterol-beta-D-glucoside and its aglycone in rats. Hua Xi Yi Ke Da Xue Xue Bao, 23, 98−101. Yeh, C. T., Ching, L. C., & Yen, G. C. (2008). Inducing gene expression of cardiac antioxidant enzymes by dietary phenolic acids in rats. The Journal of Nutritional Biochemistry, 20, 163−171. Zaid, A. (Ed.). (1999). Date palm cultivation. Rome: United Nations FAO Plant Production and Protection Paper. Zheng, Q. S., Sun, X. L., Xu, B., Li, G., & Song, M. (2005). Mechanisms of apigenin-7-glucoside as a hepatoprotective agent. Biomedical and Environmental Sciences, 18, 65−70.