What are dates fruit
Dates (Phoenix dactylifera) commonly known as date palm fruit, have been a staple food of the Middle East and the Indus Valley for thousands of years. There is archaeological evidence of dates cultivation in the area between the Euphrates and the Nile Rivers from 3,700 BC. Dates is thought to be native to the Arabian Peninsula regions, possibly originating from what is now southern Iraq 1. At a very early time, dates palm was introduced by humans to northern India, North Africa, and southern Spain and it has a major economic role in the arid zones 2. Saudi Arabia, one of the most important countries for date palm cultivation, has >10% of the world’s date palm trees (14% of the date production) and nearly 340 of ~2,000 varieties recorded around the world are grown there 3. Dates palm fruit tree (Phoenix dactylifera L.) is a strict dioecious evergreen tree capable of living over 100 productive years.
Date palm fruits are berry containing a single seed enclosed by fibrous parchment like endocarp, fleshy mesocarp and the fruit skin (pericarp). Different region give different dates which vary in shape, size, and weight. Also, they can vary in their organoleptic, physical and chemical characteristics 4. Dates is oblong in shape though certain verities might reach near spherical shape. Date palm tree starts fruiting at an average age of 5 years with an average production of 400–600 kg/tree/year and continues to produce for up to 60 years. Egypt, Iran, Algeria, Saudi Arabia, Iraq, Pakistan, Sudan, Oman, UAE, and Tunisia are the top ten date producing countries. Over 100 million date palm trees scatter on ca. 1.3 million hectare worldwide 5. The biggest contributed area is the Asian continent including Middle Eastern countries (833,351 hectare), followed by Africa with 416,695 out of which 392, 200 hectare in North Africa alone 6.
The edible part of the date palm tree has been recognized to possess many medicinal properties when consumed alone or in mixture with other medicinal herbs 7. In recent years, a huge interest in the abundant health promoting properties of date fruits had led to many pharmacological studies (in test tube and in animals) as well as the identification and quantification of different classes of phytochemicals 8. The date fruits are highly nourishing and may have numerous potential health benefits. The protective effects of fruits against chronic diseases are ascribed to bioactive non-nutrients called phytochemicals. Phytochemicals have gained increased interest among several investigators, including clinicians due to their antioxidant activity, cholesterol-lowering properties, and other potential health benefits such as chemoprevention of cancer, prevention of diabetes and cardiovascular diseases 9.
Figure 1. World map of the top ten dates fruit producing countries in 2014
The five stages of pre-maturation, maturation and ripening of dates are Hababauk, Kimri, Khalal, Rutab, and Tamer (Figure 2) 10. Depending on the maturity and ripeness stages during growth and development of the dates, different external and internal changes are observed with color, sweetness, texture and chemical composition 6. Dates contains many nutrients such as: carbohydrates, proteins, fat, minerals and vitamins 4.
The most important quality attributes to grade dates are color, flavor (sugar level), moisture (26–30%) and absence of defects such as insect, damage, cracks and surface damage. Dates fruit is good source of high nutritional value food.
Figure 2. The five growth stages of a date fruit by days post pollination
DPP = days post pollination[Source 10]
Dates provide a wide range of essential nutrients and dates is rich in carbohydrates, dietary fibers, proteins, minerals and vitamin B complex, such as thiamine (B1), riboflavin (B2), niacin (B3), pantothenic (B5), pyridoxine (B6), and folate (B9) 11. Dates flesh is found to be low in fat and protein but rich in sugars, mainly fructose and glucose. The sugar content of ripe dates is about 65%; the remainder consists of protein, fiber, and trace elements including boron, cobalt, copper, fluorine, magnesium, manganese, selenium, and zinc. It is a high source of energy, as 100 g of flesh can provide an average of 277-282 kcal (calories). Arab Bedouins historically subsisted on dates and camel milk 12. In more details, carbohydrates forms 75% of date fruit and are mostly fructose and glucose in equal ratio while date proteins are rich in amino acids that contain acidic side chain but poor in methionine and cysteine, which their side chain composed of sulfur. Minerals in date fruits are calcium, iron, magnesium, selenium, copper, phosphorus, potassium, zinc, sulfur, cobalt, fluorine, manganese, and boron 9.
Dates provide a wide range of essential nutrients, and are a very good source of dietary potassium. The date’s capacity for retaining high nutrient value when dried made it a mainstay of desert region food staples. Ten minerals were reported in dates, the major being selenium, copper, potassium, magnesium and chromium. The consumption of 100 g of dates can provide over 15% of the recommended daily allowance from these minerals. Vitamin B-complex is the major vitamin in dates. Dietary fiber (6.7-8.0 g/100 g), insoluble dietary fiber was the major fraction of dietary fiber in dates. Dates are a good source of antioxidants, mainly carotenoids and phenolics. Date seeds contain higher protein (5.1 g/100 g) and fat (9.0 g/100 g) as compared to the flesh. Date seeds are also high in dietary fiber (73.1 g/100 g), phenolics (3942 mg/100 g) and antioxidants (80400 μ mol/100 g). The caffeic acid glycoside 3-O-caffeoylshikimic acid (also known as dactylifric acid) and its isomers, are enzymic browning substrates found in dates.
A recent nutritional assessment and antioxidant analysis of 22 dates fruit varieties growing in Sultanate of Oman 13. The results of the date fruits (dried/tamar stage) revealed significantly higher moisture (15%-21%), dry matter (78%-86%), ash content (1.0%-2.0%), fiber (1.0%-2.5%), fat (0.1%-0.7%), protein (1.8%-3.8%), nitrogen (0.25%-0.55%), carbohydrates (74.5%-82.4%), and energy values (307-345.5 kcal/100 g). The antioxidant activity ranged between 40% and 86% depending upon the type of date and location. Overall, Khalas, Fardh and Khasab have significantly higher nutritional attributes; however, other varieties such as Barshi, Qush LuLu, Handal, and Khunaizi also have comparable nutritional values 13.
Figure 3. Deglet noor dates
Table 1. Dates (deglet noor) nutrition facts
|Nutrient||Unit||Value per 100 g||date, pitted 7.1 g|
|Total lipid (fat)||g||0.39||0.03|
|Carbohydrate, by difference||g||75.03||5.33|
|Fiber, total dietary||g||8||0.6|
|Vitamin C, total ascorbic acid||mg||0.4||0|
|Vitamin B-12, added||µg||0||0|
|Vitamin A, RAE||µg||0||0|
|Vitamin A, IU||IU||10||1|
|Lutein + zeaxanthin||µg||75||5|
|Vitamin E (alpha-tocopherol)||mg||0.05||0|
|Vitamin E, added||mg||0||0|
|Vitamin D (D2 + D3)||µg||0||0|
|Vitamin K (phylloquinone)||µg||2.7||0.2|
|Fatty acids, total saturated||g||0.032||0.002|
|Fatty acids, total monounsaturated||g||0.036||0.003|
|Fatty acids, total polyunsaturated||g||0.019||0.001|
|18:3 n-6 c,c,c||g||0||0|
|20:2 n-6 c,c||g||0||0|
|20:5 n-3 (EPA)||g||0||0|
|22:5 n-3 (DPA)||g||0||0|
|22:6 n-3 (DHA)||g||0||0|
|Fatty acids, total trans||g||0||0|
|Proanthocyanidin polymers (>10mers)||mg||0||0|
Figure 4. Medjool dates
Figure 2. Dates (medjool) nutrition facts
|Nutrient||Unit||Value per 100 g||date, pitted 24 g|
|Total lipid (fat)||g||0.15||0.04|
|Carbohydrate, by difference||g||74.97||17.99|
|Fiber, total dietary||g||6.7||1.6|
|Vitamin C, total ascorbic acid||mg||0||0|
|Vitamin A, RAE||µg||7||2|
|Vitamin A, IU||IU||149||36|
|Lutein + zeaxanthin||µg||23||6|
|Vitamin D (D2 + D3)||µg||0||0|
|Vitamin K (phylloquinone)||µg||2.7||0.6|
|Fatty acids, total trans||g||0||0|
Phytochemicals in date fruits
Phytochemicals are plant-derived chemicals which may give health benefits when taken as a medicine drug or as a part of daily diet. They are classified into two main categories: primary metabolites, which occur in all cells and play an essential role in the reproduction and metabolism of those cells, for example nucleic acids, the common amino acids and carbohydrates (sugars); secondary metabolites such as terpenes (a group of lipids), phenolics (derived from carbohydrates), alkaloids (derived from amino acids) which are characteristic of a limited range of species and have a biological effect on other organism 15. Many of biologically active constituents of medicinal, commercial and poisonous plants are classified as secondary metabolites.
Dates fruit is rich in phytochemicals such as carotenoids, polyphenols (e.g., phenolic acids, isoflavons, lignans, and flavonoids), tannins, and sterols 16. The concentration and composition of these constituents are widely varied depending on several parameters, including date variety, stage of fruit picking, storage, postharvest processing, the geographical origin of the dates and soil conditions 17. Several researchers have reported that the chemical constituents and functional composition of date fruits are dramatically changed during date maturing period with increasing in levels of reducing sugars, while fiber, mineral, and vitamin levels decreasing steadily 17.
The currently characterized polyphenols and average amounts in dried and fresh dates and date seeds are listed in Table 3. Nineteen different flavonoid glycosides of luteolin, quercetin, and apigenin have been found to exist in dates in methylated and sulfated forms. Analysis of mass spectral data has suggested that sulfates are linked to these flavonol glycosides as opposed to phenolic hydroxyls, making dates the only fruit or vegetable known to contain flavonoid sulfates. Anthocyanins have only been found to exist in fresh fruit, and carotenoids decrease rapidly as the fruit ripens 18. Total phenolic content in fresh dates is six times higher than in dried dates 19. However, the processes that allow drying and thus preservation of dates affect the bioavailability of the polyphenolic compounds. Upon drying, the date loses up to 30% of total carotenoids and 93% of anthocyanins. On the other hand, for the dried fruit, there is a statistically significant increase of 22%–153% in total phenolics per 100 g weight, differing by variety 20. Leading the way in this increase are phenolic acids, which have been found to have a statistically significant increase of 64%–107% in the dried fruit 21. Storage of dried dates leads to oxidation of polyphenols, a potential explanation for this conflicting data.
Table 3. Polyphenols in dates, and mean amounts if known.
(mg per 100 g)
(mg per 100 g)
(mg per 100 g)
|Phenolic acids||Hydroxybenzoic acids|
|Luteolin||Proanthocyanidin dimer (total)||55.8|
|Proanthocyanidines||Proanthocyanidin trimer (total)||61.3|
Carotenoids considered as a major class of phytochemicals occur in the lipid fractions of dates fruit. They are precursors of vitamin A, which plays a central role in vision, and protects the cell from deleterious effects of free radicals by acting as antioxidants 22. Carotenoid classification is depending on the presence or absence of oxygen in the molecule, they can be divided into two main subclasses: xanthophylls (contain oxygen atom) and carotenes (lack oxygen atom). Boudries et al. 23 studied the carotenoid composition for three different dates fruit varieties at three edible maturation stages (Khalal, Rutab, and Tamr) and they found that dates contain lutein and β-carotene as major carotenoids. Neoxanthin, violaxanthin, and antheraxanthin were identified in date fruits in lesser amount (Figure 5). Al Farsi et al. 24 analyzed the total carotenoids for three date fruit varieties (Fard, Khasab, and Khalas) and they found that Khalas has the highest amount of carotenoids as expected as this variety has a yellow color. They also reported destruction of total carotenoids after sun drying of date fruit ranged between 4 and 30%. Dried dates fruit is a moderate source of carotenoid (0.97 mg/100 g) compared to other dried fruits, e.g., figs and apricot: 0.032 mg/100 g and: 2.20 mg/100 g respectively 16.
Figure 5. Date fruits carotenoids
Phytosterols and phytoestrogens
Phytosterols are another major phytochemicals that found in the lipid soluble fraction of the date fruit. These compounds are exclusively occurring in plants with chemical structure similar to that of cholesterol. Approximately 200 phytosterols exist in nature and many of them are found in vegetables and fruits (Amorós et al., 2009). Date fruit at tamer stage contains several phytosterols. Back in 1978, cystalline plant sterol mixture was first isolated from the edible part of date fruit and has been identified to include β-sitosterol, stigmasterol, campesterol, and isofucosterol (Figure 6) 25. However, the difference in the phytosterol composition among the date fruit varieties and its ripening stages is still unclear and therefore make it an important line for advance research. Moreover phytoestrogens are natural compounds that can bind estrogen receptors and exert diverse estrogenic or antiestrogenic effects 17. Thompson et al. 26 studied the phytoestrogens content in date fruit and they identified several phytoestrogens including formononetin, daidzein, genistein, glycitein, matairesinol, lariciresinol, pinoresinol, secoisolariciresinol, and coumestrol (Figure 6).
Figure 6. Dates fruit phytoestrols27]
Phenolic acids considered as one of the main aromatic secondary plant metabolites, containing hydroxyl function located on aromatic benzene ring with one or more carboxylic acid groups. Phenolic acids can be divided into two main classes: benzoic acid derivatives of which contain seven carbon atoms and cinnamic acid derivatives of which contain nine carbon atoms. They considered as effective antioxidant because they act as free radical captor or scavenger. Several research groups reported that dates are rich in phenolic acids 28. Al Farsi et al. 24 studied three different Omani date fruits (Fard, Khasab, and Khalas) and found to contain the following benzoic acid derivatives; p-hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid and syringic acid, while the cinnamic acid derivatives were; o-coumaric acid, p-coumaric acid, caffeic acid, and ferulic acid (Figure 7). In another study of seven different varieties of date fruits cultivated in Algeria, Mansouri et al. 29 identified the main phenolic acids including p-coumaric acid, ferulic acid and sinapic acid. Moreover, three different isomers of 5-o-caffeoyl shikimic acid were identified, in addition xanthoxylin acid, hydrocaffeic acid, and coumaroylquinic acid were reported (Figure 7). Karasawa et al. 30 identified protocatechuic acid, syringic acid, caffeic acid, ferulic acid, and chlorogenic acid in the date extract using ultra performance liquid chromatography by comparing the retention time and UV spectrum of the peaks of these compounds with those of standard phenolic acids (Figure 7). The major phenolic acids in Saudi dates fruit varieties were gallic acid, p-coumaric acid, and ferulic acid derivatives 31. Recently, Borochov-Neori et al. 32 studied the phenolic composition of two dates varieties, Amari and Hallawi, at Tamr stage. They detected five and seven phenolic acids constituent in Hallawi and Amari, respectively. The major component of the phenolic fraction was ferulic acid and a trace amount of coumaric acid for both varieties. Amari found to contain mostly caffeic acid derivatives, while salicylic acid was the most abundant phenolic acid in Hallawi dates. Protocatechuic acid, vanillic acid, gallic acid, syringic acid and p-coumaric acid were detected in three different Tunisian date fruit varieties (Figure 7) 33. Lemine et al. 34 found that the amount of phenolic acids in Khalal stage of date is significantly higher than in the fully mature Tamer stage, 0.729 g/100 g, and 0.559 g/100 g (wt/wt), respectively.
Moreover, Awad et al. 35 reported that the quantity of phenolic compounds decreased, with a 25% loss through the ripening stages from the Khalal to the Tamar in date fruits cultivar from Tunisia. However, Al-Najada and Mohamed 36 studied the change of total phenolic contents of Khalas and Shishi date fruits during storage at 4°C and they reported that the phenolic contents significantly increased after 6 months, while after 12 months of storage the phenolic contents increase up to about double the amount.
Figure 7. Dates fruit phenolic acid compounds
Flavonoids are large family of polyphenolic plant derived secondary metabolites, comprise of 15 carbons skeleton containing two aromatic benzene rings A and C chemically bound via a heterocyclic pyrane ring C and this skeleton is often substituted with multiple substitution patterns (Figure 8). Flavonoids are classified into several subgroups, including flavones, flavonols, flavanones, flavanonol, isoflavones, isoflavonone, flavan-3-ols, and anthocyanidins. Flavonoids are found in a variety of fruits and vegetables with notable health benefits as antioxidant and anti-inflammatory 37. Hong et al. 38 studied the flavonoid glycoside and procyanidin compositions of date fruit, variety Deglet Noor, harvested at Khalal stage of maturity by liquid chromatography-electrospray ionization/tandem mass spectrometry and found that it contain 13 flavonoid glycosides of apigenin, luteolin, and quercetin, 19 in isomeric forms (Figure 8), in addition they reported flavonoid sulfates. Chaira et al. 39 reported that Korkobbi variety has the highest level of flavonoids among 10 Tunisian date varieties, as a consequence, it shows the highest antiradical efficiency of this cultivar. In Oman, the total flavonoid content has been investigated for three major date varieties; Fardh, Khasab, and Khalas at two edible maturation stages; Rutab and Tamr 40. Michael et al. 41 found a new diosmetin glycosides; diosmetin 7-O-β-L-arabinofuranosy (1→2)-β-D-apiofuranoside (Diosmetin 1) and diosmetin 7-O-β-D-apiofuranoside (Diosmetin 2), which was isolated from acetone extract of date fruits (Figure 8).
In another study on 11 different Saudi date fruit varieties, apigenin, luteolin, quercetin, isoquercetrin, and rutin were identified 31. Kaempferol, a natural flavonol, derivatives were identified in Amari and Hallawi date fruits, where Amari contained five flavonol in a significant amount and Hallawi contained one major flavonol 42. Lemine et al. 34 reported that the total content of flavonoid decrease significantly from Khalal stage to Tamer stage for the seven different date fruits varieties that they examined. Another study showed that the flavonoid content reduced during maturity stages from Khalal to Tamer stage for four different studied Tunisian date fruit varieties 43. Al Farsi et al. 24 measured the content of anthocyanins in fresh and dried date fruits and these were identified only in fresh dates, this might be due to the destruction after expose it to the sun. It was reported that enzymatic and non-enzymatic browning reactions can cause the destruction of anthocyanins during drying and storage period 44. While pelargonin, an anthocyanin was identified in date fruits (Figure 8) 30. Moreover, the total flavanol, including catechin in the edible part found to be more than that in the date pits 45.
Figure 8. Dates fruit flavonoids
Health benefits of dates
The benefits of eating dates are attributed to its polyphenolic content 46. Plant polyphenols are naturally occurring compounds found in fruit, vegetables, and in products such as fruit- and vegetable-derived sugars, juices, and oils. They are secondary metabolites in the plants they are produced from, serving as a defense system to ultraviolet (UV) light or pathogens 47.
The general chemical structure of polyphenols dictates their categorization into phenolic acids, flavonoids, stillbenes, ligans, and a multitude of derivatives and is a strong predictor of their rate of absorption and resulting serum levels 48. Figures 7 and 9 shows structural formulas of some of the varying polyphenols found in dates. All polyphenols arise from a common intermediate, known as phenylalanine, or a close precursor thereof called shikimic acid 47. The products formed from these basic constituents are diverse, leading to a vast array of polyphenol protectants available to plants and humans alike.
It is theorized that the health benefits of the synergy among polyphenol components in whole foods in our diet will far outweigh the benefits of any singular polyphenol 48. Many researchers have thus opted to study whole fruit extracts to glean an understanding of the effects of the whole as opposed to its parts.
Plant polyphenols have been found to possess a range of effects: estrogenic and anti-estrogenic activity, anti-proliferative activity, induction of cell cycle arrest and apoptosis, prevention of oxidation, regulation of the host immune system, anti-inflammatory activity, modulation of effect of cytochrome P450 enzymes involved in activation of pro-carcinogens, upregulation of genes producing anti-oxidant enzymes, and the ability to change cellular signaling 48. The challenge remains in standardizing these products for therapeutic and preventative consumption.
Dates have been found to contain extremely high levels of phenolics, hypothesized to have formed due to exposure to extreme temperature and climate in comparison to other fruit 19. However, their composition can be vary from cultivar to cultivar depending on soil conditions and agronomic practice, for example, the nutritional quality of date fruits alters among varieties grown in Algeria 49 and Oman 39, Bahrain 50, and Sudan 51. Guo et al. 52 studied the antioxidant activities of 28 fruits commonly consumed in China and they found that date fruits possess the second highest antioxidant activity after Hawthorn. In another study, Saafi et al. 53 investigated the effect of aqueous date fruit extract (Deglet Noor variety) on the protection against oxidative damage as well as hepatotoxicity induced by subchronic exposure to dimethoate on rat liver and the data showed that the extract repaired the damage of the liver. In different study, Mansouri et al. 29 examined the immunomodulatory effects of a hot water extract from date at tamer stage, prune and fig fruit in mice. They found that date fruit extract promote the cellular system more than prune and fig extract. Moreover, it has been reported that diosmetin glycosides (diosmetin 1 and 2, Figure 8 – flavanoids) can increase the insulin excretion and stimulate the enzyme glycogen synthase, which maintain homeostasis of blood glucose levels in-vivo using alloxan diabetic male rats 40. In addition, the treatment of alloxan diabetic male rats by these two compounds showed a highly increase in serum testosterone level accompanied with a significant decrease in total and prostatic acid phosphate activities 40. El Sohaimy et al. 54 measure the antimicrobial activity of some Egyptian dates fruit against five pathogenic bacterial strains and they found that the water and ethanol extracts has a strong antibacterial activity. Al-Yahya et al. 55 studied the cardioprotective effect of lyophilized aqueous date fruit extract (Ajwa variety) in test tubes and in animals and they found that it enhance the cardiomyoblast cell proliferation by up to 40%, prevented the consumption of endogenous antioxidants and inhibited lipid peroxidation. Garba and Galadima 56 investigated the antimicrobial potential of date fruit extract on the bacteria, salmonella spp. and shigella spp., which cause diarrhea. The extracts from water, methanol and petroleum ether showed a significant activity as anti-diarrhea. Borochov-Neori et al. 42 investigated the antioxidant and antiatherogenic properties of date fruit (Amari and Hallawi varieties) at Tamr stage extract, prepared by acetone/water (7:3, v/v) solution containing 0.5% acetic acid. Several methods have been used to measure the antioxidant activities of these varieties and were reported to possess antioxidant activity comparable to vitamin C. Moreover, they studied the effect of the isolated phenolic acid and flavonol fractions from date fruits in the extent of cholesterol efflux and they found that the flavonol fractions enhanced cholesterol removal from macrophages. This positive antioxidant effect might protect the cell membrane from being oxidized by the effect free radicals generated both extra- and intracellularly 42. Lemine et al. 34 studied the anti-oxidant activity of seven different Mauritanian date fruits varieties at two edible stages (Khalal and Tamr) and they found that Khalal has higher antioxidant compare to Tamr stage). While Al Farsi et al. 24 reported the antioxidant activity of three date fruit varieties grown in Oman, namely; Fard, Khasab, and Khalas. The results show that Khalas to possess higher antioxidant activity.
Figure 9. Polyphenols found in dates
A 2009 study was done on the effects of Medjool and Halawi dates on serum glucose and lipid levels and on serum oxidative status 57. Researchers quantified total soluble phenolics in Hallawi and Medjool dates. Generally, the Hallawi variety dates was found to have a higher phenolic content of approximately 619 mg/kg in pyrogallol equivalents, and 1000 mg/kg in tannic acid equivalents, as compared to Medjool dates that contained approximately 517 mg/kg in pyrogallol equivalents and 763 mg/kg in tannic acid equivalents 57. The effects of oral consumption of both varieties of dates on serum oxidative status in 10 healthy, non-smoking subjects ranging in age from 20–40 years were quantified. It was found that 100 g of Hallawi dates consumed daily for four weeks significantly reduced basal serum oxidative status, AAPH-induced serum lipid peroxidation, and increased serum PON1 aryl esterase activity, an enzyme necessary to protect serum lipoproteins from oxidation. While these results show promise for future work, several caveats must be considered. Aside from the aforementioned demographics, no further demographic information was given for the subjects, and no clinical standard of “healthy” had been agreed upon by clinicians. In lieu of a control group, the subjects’ basal serum oxidative status was measured via TBARS assay prior to ingesting Medjool dates after the four weeks had elapsed, again after a four week washout period prior to ingesting Hallawi dates, and then again after ingesting Hallawi dates for the allotted four-week timeframe 57. While this allows a contrast that is a true measurement of the subjects’ change in oxidative status, a separate control group that had undergone the same timing in measurements without the introduction of a treatment, or a null treatment, would have strengthened the study.
Date fruit may have a potential health benefits against many types of cancer as it suggested by experimental evidence and the phytochemical composition. Al-Sayyed et al. 58 reported the potential cancer preventive effects of dates fruit. They found that increase consumption of dried dates fruit reduced significantly the incidence rate of mammary cancer, palpable tumor multiplicity, tumor size and weight compared to the positive control group. Eid et al. 59 studied the whole date fruit extract and its polyphenol-rich extract, both extracts were prepared from methanol/water (4:1, v/v) containing 10% of 1 molar sodium fluoride (NaF) solution, found to inhibit Caco-2 cell growth, indicating that both were capable of probably acting as anti-proliferative agents in-vitro. According to their results, consumption of date fruits may promote health condition of the colon by increasing the growth of beneficial bacterial and inhibiting the proliferation of colon cancer cells. In another study, Zangiabadi et al. 60 studied the effect of aqueous date extract on diabetic polyneuropathy in streptozotocin induced diabetic rats and they reported that date extract was able to prevent the diabetic aggravation and in enhancing pathological parameters of diabetic neuropathy. Pujari et al. 61 reported that date extract, prepared using methanol/water (4:1, v/v), gives significant neuroprotection against cerebral ischemia induced by bilateral common carotid artery occlusion. Souli et al. 62 suggested that aqueous date fruit extract accelerate the gastrointestinal transit activity and reduces the risk of constipation. In a very recent study, Belmir et al. 63 investigated the antifungal activity of aqueous date fruit (Ajwa variety) extract at Tamr stage with the amphotericin B, an antifungal drug. They reported that therapeutic index of amphotericin B increased significantly with the extract and the cytotoxicity induced by amphotericin B test showed that the aqueous date extract prevents cytotoxicity of red blood cells. Kchaou et al. 64 examined the cytotoxic property of Tunisian date fruits, using methanol/water (4:1, v/v), and the result showed that the human cells growth has been significantly decrease after treatment with the date extract. In another study the antibacterial properties and antioxidant activity of Saudi date fruits variety Ajwa, Safawi, and Mabroom, as well as Iranian date fruits variety Mariami was investigated. The date fruits were treated with polar extraction solvents (methanol or acetone) at 4°C, while the extracted materials were stored at −20°C. The storage stability of total anthocyanin content was also studied and shows that date variety Mariami had the highest total anthocyanin content content while Mabroom had the lowest total anthocyanin content. The total amount of extracted phenolic compounds from dates using methanol as solvent found to be a better solvent compared to acetone. It was reported that different cultivars exhibited different antibacterial properties. The methanolic extract of Ajwa date variety was reported to exhibited antibacterial activity among all studied bacteria: Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Serratia marcescens 65. A recent study by Taleb et al. 66 investigated the pharmacological effect of date syrup, which made from the edible part of dates fruit, and has been found to be useful in the treatment of several diseases with etiologies involving inflammation and angiogenesis. The authors reported that the polyphenolic compounds occur in date syrup reduce angiogenic responses, e.g., tube formation, cell migration, and matrix metalloproteinase activity in an inflammatory model by exhibiting anti-inflammatory activity mediated by the prostaglandin enzyme cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in endothelial cells. Inflammation was found to be reduced by the administration of the date fruit syrup polyphenolic compounds at 60 and 600 μg/mL, as well as suppressed many stages of angiogenesis, including endothelial matrix metalloproteinase activity, invasion, tube formation and cell migration. Interestingly, date syrup shows no cytotoxicity effect. Moreover, the polyphenolic compounds of date syrup were found to significantly reduce the expression of COX-2 and VEGF induced by tumor necrosis factor-alpha at both protein level and gene expression in comparison to untreated cells 66. Most recently a study by Khan et al. 67 reported the effects of date, Ajwa variety, on cancer therapy; therefore date fruits might be used as useful as an adjunct therapy with conventional chemotherapeutics to achieve a synergistic effect against breast cancer.References
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