Journal of Nutraceuticals and Food Science

Keywords

Phoenix dactylifera; Islamic remedy; Therapeutic potentials

Introduction

Natural products can be good remedies because they are inexpensive and easy to access. Some herbs are recommended as a remedy for some diseases by the Prophet Mohammed [1] as he said dates cure several disorders. The importance of dates has been documented in the Qur’an in Surah Maryam, at the point when Mary brought forth the Christ Jesus under a palm tree, she heard a voice advising her: “Shake the trunk of the palm tree towards thee: it will drop new, ready dates upon thee. Eat, then, and drink, and let thine eye be!” (Qur’an 19: 25-26) [2]. The health benefit of Ajwa dates has been documented in hadith as Saud (R.A) narrated that I heard Allah’s Apostle saying, “If Somebody takes seven Ajwa dates in the morning, neither magic nor poison will hurt him that day” [3].

Date palm (Phoenix dactylifera) belongs to the Arecaceae botanical family, which contains about 200 genera with around 3,000 species [4]. P. dactylifera have been developed in the Middle East over the last 6000 years [5]. Numerous research studies have proven the preventive effect of P. dactylifera against different environmental chemicals that may be toxic for some tissues in animal and human [6]. Phenolics of powerful antioxidants have been isolated from P. dactylifera such as ferulic, gallic, catechin, chlorogenic, caffeic, coumaric, resorcinol, protocatechuic, dactyliferic, 3-o-caffeoylshikimic, sinapic, p-hydroxybenzoic, vanillic, syringic, procyanidin and isochlorogenic acids [7-9]. The anthocyanins, apigenin, isoquercetrin, quercetin, quercetrin, procyanidins, luteolin and rutin constitute the flavonoid content of P. dactylifera. Moreover, P. dactylifera contains considerable amounts of antioxidant vitamins C, A and E [10-12].

The therapeutic potentials of P. dactylifera in this study were searched in PubMed and Google scholar databases and will be discussed in this review.

Therapeutic Potentials of Phoenix dactylifera

Antioxidant activity

Oxidative stress is an imbalance between oxidant production and antioxidants. Enzymatic and non-enzymatic antioxidants reduce the reactive oxygen species (ROS) induced by oxidation. Superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione S-transferase (GST) are the enzymatic antioxidants of concern. P. dactylifera has antioxidant potential via its phenolics, flavonoids and small molecules such as vitamin C, vitamin E and GSH. These antioxidant constituents of P. dactylifera may directly react with ROS to destroy them by accepting or donating electrons to eliminate the unpaired condition of ROS, or they may indirectly decrease the cellular free radicals by enhancing the activities and expressions of antioxidant enzymes that lead to prevention of lipid peroxidation, DNA damage and protein modification.

An in vitro study was conducted to evaluate the antioxidant potential of P. dactylifera fruit aqueous extract by determination of its hydroxyl-radical-scavenging potential. Various concentrations of P. dactylifera extract in a Fe²⁺/ ascorbate/EDTA/H₂O₂ system were measured with a thiobarbituric acid method. They also studied the superoxide scavenging potential of date fruit extract in a photo-reduction of riboflavin assay measured w nitroblue tetrazolium reduction method. There was a significant dose dependent relationship in the inhibition of hydroxyl-radical inhibition by P. dactylifera extract with complete inhibition shown at a concentration of 4.0 mg/mL [13]. The antioxidant effects of P. dactylifera were found to hinder lipid peroxidation and inhibit free radicalmediated oxidation of lysine, arginine, and proline residues of proteins, leading to prevention of the formation of carbonyl derivatives. This potential of P. dactylifera may be due to their total phenolic content, flavonoids, vitamins C, A and E and β- carotene and GSH. However, the authors didn’t quantify the active ingredients present in P. dactylifera and studied only the aqueous extract.

A 2015 study was done on the antioxidant potentials of P. dactylifera fruit’s phenolic or flavonoid fractions from two date varieties, Amari and Hallawi, through determination of ferricreducing antioxidant power, free radical scavenging capacity, inhibition of Cu²⁺ induced LDL oxidation, and enhancement of HDL-mediated cholesterol efflux from macrophages [14]. The flavonoid fraction was found to have greater inhibitory activity in preventing LDL oxidation than the phenolic fractions, with IC50 of 9-31 nmol/GAE mL versus 85-116 nmol/GAE mL, respectively. The phenolic and flavonoid fractions of both Amari and Hallawi dates exhibited variable capacities to reduce ferric ions, scavenge radicals, and inhibit LDL oxidation along with increased LDL-C efflux from macrophages by flavonoid fractions.

Another in vitro study to evaluate the antioxidant activity of different Tunisian common varieties of P. dactylifera was done by Chaira et al [15]. The authors evaluated the phenolic content (54.66 mg/100 g fresh weight Korkobbi) and flavonoids (54.46 quercetin equivalents/100 g fresh weight Korkobbi). The percentage of lipoperoxyl radical inhibition reached 83% in the Korkobbi variety, while it was about 95% in the Rotbi variety. The antioxidant activity of each variety differs according to the phenolics and flavonoids; Korkobbi is the most potential variety against free radicals. A similar study confirmed a high positive correlation between total phenolics in methanolic extract of Mauritanian P. dactylifera varieties (Tamr and Blah fruit) and trolox equivalents antioxidant capacity, suggesting that phenolics were the major contributor to the antioxidant activity [16].

Anticancer activity

Cancer is a lethal disease that attacks more than one-third of the world’s population. Smoking, viral infection, chemicals, radiation, environmental factors, and dietary factors are the main predisposing causes of cancer. Chemotherapy, radiotherapy and surgery are the primary conventional treatments along with complementary and alternative therapies of natural origin. Phenolics and flavonoids of medicinal plants have been used as powerful anticancer drugs through up-regulation of anti-apoptotic molecules such as p53, caspases and Bcl-2-associated X protein (Bax) or by downregulation of apoptotic molecules as Akt, B cell lymphoma-2 (Bcl-2) and nuclear factor κB (NFκB) [17].

One study of digested date extract (DDE) and polyphenolrich extract (DPE) tested the growth inhibition of human epithelial colorectal adenocarcinoma (Caco-2) cells before and after pH-controlled batch culture fermentation in comparison to untreated cells [18]. In 24-well plates, Caco-2 cells were seeded at low confluence (5×10⁴ per well) and exposed to DDE and DPE (0.2 mg/mL). After 24, 48 and 72 h the cells were harvested and fixed by the addition of 125 μl ice-cold trichloroacetic acid. The medium was removed and the cells were washed and total biomass determined using sulforhodamine B. At 48 h, DDE had a significantly greater growth inhibition percentage of Caco-2 cells than DPE, with DDE inhibiting about 90%. After 48 h fermentation, the DDE induced 70% inhibition while DPE induced 30% inhibition.

β-glucan is another phytochemical constituent of P. dactylifera that exhibits anticancer activity. β-glucan has been isolated from Libyan P. dactylifera and exhibits potent antitumor activity correlated to their (1→3)-β-D-glucan linkages. This was the first report on β-glucan antitumor effect [19]. There is a completed trial that investigated the anticancer effect of low molecular weight β-glucan derived from oats in cancer cells: human melanoma (Me45), human epidermoid carcinoma (A431) and normal immortal human keratinocyte (HaCaT) and murine macrophages (P388/D1) [20]. The β- glucan significantly deceased cancer cells’ viability, while no toxic effect on the normal cells was seen. Moreover, β-glucan induced a significant expression of caspase-12, the inflammatory caspase, in both cancer cell lines (Me45 and A431), while in HaCaT cells was significantly lower and in P388/D1 cell line was negative. The data revealed strong anticancer properties of new low molecular weight β-glucan from oat. This study is of particular interest and directs researchers to investigate the anticancer effect of β-glucan isolated from P. dactylifera against numerous cancer cell lines in both in vitro and in vivo studies.

Hepatoprotective activity

The liver is a vital organ of the digestive system that regulates a wide variety of anabolic and catabolic biochemical reactions necessary for normal vital functions. It protects organisms from toxic chemicals through its capacity to convert lipophilics into more water-soluble metabolites that can be efficiently eliminated from the body via urine. This protective ability of the liver is from the enzymes that catalyze the oxidation, reduction and hydrolysis (Phase I) and conjugation (Phase II) of functional groups on drug and chemical molecules. Some toxic chemicals such as carbon tetrachloride (CCl₄), thioacetamide, dimethoate and dichloroacetic acid have induced oxidative stress and morphological changes in liver that causes liver injuries and defects in hepatic detoxification ability; these changes that can be restored by P. dactylifera because it enhances the liver’s detoxification ability will now be discussed.

An example is a study on the protective effect of Siwa P. dactylifera flesh aqueous (1:3 w/v) against CCl₄ hepatotoxicity in rabbits [21]. Rabbits were pretreated with a single dose of 15 mL of Siwa date palm extract orally. CCl₄ solution was prepared in paraffin oil (50 % v/v) and injected subcutaneously with a dose of 1.0 and 2.0 mL CCl₄ solution/kg. P. dactylifera extract significantly ameliorated the elevated levels of malondialdehyde (MDA) and GSH depletion in the liver tissue caused by CCl₄ along with marked ameliorations of elevated alanine transaminase (ALT) and aspartate transaminase (AST). Moreover, P. dactylifera induced an elevation in serum immunoglobulin M (IgM), immunoglobulin G (IgG), immunoglobulin (IgA) levels.

A study of CCl₄ in rats and the hepatoprotective effect of both P. dactylifera flesh and seeds were conducted by soaking either P. dactylifera flesh or seeds powder in distilled water in a ratio of 1:3 w/v [22]. Rats were treated by either extract before and after CCl₄ intraperitoneal injection. The results revealed a significant reduction in elevated ALT, AST, and alkaline phosphatase (ALP) activities due to CCl₄ in rats subjected to both pre- and post-treatments with the aqueous extracts of P. dactylifera flesh and seeds. To complete the experimental design of this study, we recommend an additional group injected by olive oil alone as a control because the CCl₄ was prepared in olive oil and injected intraperitoneally at a dose of 0.2 mL/100 g body weight of rats.

There have been several studies of the ameliorative effect of the aqueous extract of P. dactylifera against the elevated serum hepatic markers due to induced hepatotoxicity by thioacetamide (400 mg/kg/single dose), dimethoate (20 mg/kg/day) and dichloroacetic acid (0.5 and 2 g/L water) in rats [23-25]. P. dactylifera extracts induced significant reduction in the elevated activities of serum ALT, AST, ALP, lactate dehydrogenase (LDH) and γ-glutamyl transferase (γ-GT) due to chemicals. The topics of these studies are of great importance toward investigating the protective role of P. dactylifera against environmental chemicals that have serious hazards. Further studies on the protective role P. dactylifera against various pollutants were recommended for future research.

Nephroprotective activity

The kidneys are a vital organ for detoxification of environmental chemicals or drugs by methylation, sulphation, glucuronidation, glycine conjugation and glutathione conjugation by GST. Metabolism of drugs by the kidneys produces toxic metabolites and ROS that favor renal injury through lipid peroxidation, protein damage, and DNA strand breaks. In the same context, numerous studies that evaluated the nepheroprotective activity of P. dactylifera have proven that the protective P. dactylifera effect against various nephrotoxicity may be due to the phenolics and antioxidant vitamins contents present in P. dactylifera and will now be discussed.

A study of the protective role of P. dactylifera seeds aqueous extract against diabetes induced by streptozotocin in rats has been done [26]. Orally administered extracts to diabetic rats at a dose of (1 g/kg/d) for 4 weeks significantly ameliorated the elevated levels of glucose, urea, creatinine, ALT, and AST due to streptozotocin. Furthermore, significant enhancement in GSH level and SOD, GST and CAT enzyme activities with significant reduction in thiobarbituric acid reactive substances (TBARS) and nitric oxide levels in both liver and kidneys were stated for the P. dactylifera treated groups. The enhancement in both liver and kidney functions was attributed to the antioxidant property of P. dactylifera seeds extract.

In another study the renal protective activity of proanthocyanidin- rich date seed extract against CCl₄-induced toxicity model in rats in a dose of 100 mg of extract/kg rat was evaluated [27]. Relative to the control CCl₄-intoxicated group, pretreatment with extract significantly suppressed the elevated serum levels of creatinine, 5.41 versus 7.07 mg/dl. The authors attributed the protective effect against CCl₄ nephrotoxicity to the free radical scavenging potentials of proanthocyanidin- rich date seed that was determined by a significant decrease in MDA in renal tissue.

In a study of the protective role of P. dactylifera flesh and seeds extracts against gentamicin-mediated nephrotoxicity, rats were given either the P. dactylifera flesh extract (50 % w/w) mixed with the food or the seeds extract in the drinking water in a ratio of 2:1 w/v [28]. Gentamicin was injected intramuscularly at a dose of 80 mg/kg/day during the last 6 days of treatment after 28 consecutive days of P. dactylifera extract treatments. The P. dactylifera flesh and seeds significantly decreased plasma creatinine and urea levels due to gentamicin nephrotoxicity in comparison to control. This antioxidant activity may be attributed to melatonin, vitamin E, and ascorbic acid components of P. dactylifera. Characterization and quantification of antioxidant components of both P. dactylifera flesh and seeds extracts were not done in this study by HPLC or GC-MS; these techniques may be helpful in understanding the mechanism by which extracts protected the rats against gentamicin nephrotoxicity.

Another study investigated the nephroprotective activity of P. dactylifera in rats. Two experiments were done; in the first, rats received daily treatment with date extract of 4 mL/kg, 30 minutes prior to oral administration of dimethoate 20 mg/kg for 2 months as a protective experimental design. In the second experiment, rats received dimethoate alone for a month and then began receiving the experimental treatment in the second month [29]. In both experiments, P. dactylifera groups had no significant difference in plasma creatinine, urea, uric acid, and renal SOD when compared to control, while MDA levels were significantly decreased due to P. dactylifera in comparison to the dimethoate injected group. Further studies should be done to investigate the protective role of P. dactylifera along with different nephrotoxic drugs or environmental chemicals though molecular and histopathological studies on the anatomical elements of the kidney, such as the glomerulus, tubules, and medulla.

Neuroprotective activity

Brain injuries are of numerous etiologies involving genetic, metabolic, nutritional, and infectious mechanisms in antenatal or postnatal periods. Both peripheral neurotoxicity and central neurotoxicity associated with chemotherapies as paclitaxel, cisplatin, cytarabine, ifosfamide and methotrexate or environmental neurotoxicants as lead and mercury.

In a study on the neuroprotective effect of P. dactylifera against bilateral common carotid artery occlusion, rats were pretreated with methanolic extract of P. dactylifera fruits at a dose of 30, 100 and 300 mg/kg for 15 consecutive days [30]. All depletion induced by ischemia in GSH levels and SOD and CAT activities was attenuated by P. dactylifera extract at a dose of 100 and 300 mg/kg, while no significant changes were recorded at the low dose (30 mg/kg). Hence, the P. dactylifera methanolic extract protected against induced oxidative stress and neural damage in a dose-dependent manner.

Diabetic neuropathy in streptozotocin-induced diabetic rats and the effect of P. dactylifera fruits aqueous extract has been studied [31]. Diabetes was induced in rats by intraperitoneally injection of 45 mg/kg freshly prepared streptozotocin dissolved in 0.1 mol/L citrate buffer. After one week, fasting blood sugar was determined and rats with fasting blood glucose levels over 200 mg/dl were considered diabetic. After confirmation of diabetes, aqueous extract of P. dactylifera in a dose of 4 mL/kg rats was administrated by gavage daily for 6 weeks. P. dactylifera induced significant reductions in grooming frequency and sciatic motor nerve conduction velocity in comparison to control, whereas in rearing status, total distance moved, and mobility duration no significant changes were recorded. It would be useful for this study to be extended to include multiple doses to decide on the most suitable one to induce neuroprotection.

Gastrointestinal protective activity

Prophet Muhammad recommended Muslims to break their fasting during holy month of Ramadan (iftar) with date fruits. Research studies have proven that eating date fruits after fasting has benefits for our nutrition and gastrointestinal tract (GIT) health [2,10]. The Prophet said, "When you break the fast, you should do it with a date-fruit for there is blessing in it, and if you do not find a date-fruit, break it with water for it is pure". Date-fruits are easy to digest so they don’t exhaust the empty stomach of the fasting person to receive the food after being inactive throughout the day, activating the release of digestive secretions and preventing constipation.

In a 2003 study, the GIT transit time effects of different extracts of P. dactylifera fruit and seeds in comparison to yohimbine, a drug used to increase the GIT transit time, and clonidine, a drug used to decrease GIT transit time, were studied in doses of 1 mg/kg and 2 mg/kg, respectively, by intraperitoneal injection in mice [32]. The aqueous extracts of the P. dactylifera fruit and seeds were prepared by adding distilled water to coarsely pounded P. dactylifera fruit in a ratio of 3:1 (w/v), and leaving for 48 h t 4ºC with continuous stirring. Parts of aqueous extracts were dialyzed by dialysis tube running tap water for 24 h. The dialyzed aqueous extract was kept refrigerated and used daily for 14 consecutive days. Moreover, the P. dactylifera fruit and seeds were added in a ratio of 1:3 (w/v) to ethanol at 40C with continuous stirring. Each mouse was fasted from food but not water 16 h prior to administration of extracts of either P. dactylifera fruit or seeds by oral gavage at doses of 0.01, 0.02 or 0.04 mL/kg. After 2 hours, all animals were given a test meal containing charcoal and gum Arabic in water. Thirty minutes after that they were stunned and sacrificed by cervical dislocation. The travelled distance of the charcoal column along the small intestine was determined to evaluate GIT transit time. Aqueous and ethanolic extraction of P. dactylifera fruits and seeds were emptied from the gastrointestinal tract contents in a dosedependent manner.

Another study compared GIT transit time due to P. dactylifera sap (0.4 and 4 mL/kg rat), aqueous P. dactylifera pulp extract (150 and 300 mg/kg rat), clonidine (1 mg/kg rat) and yohimbine (2 mg/kg rat) orally [33]. The P. dactylifera sap and aqueous P. dactylifera pulp extract significantly increased the GIT activity in rats in a dose-dependent manner that confirmed their use in traditional Tunisian medicine for the treatment of constipation. For further study, the phytochemical composition of P. dactylifera sap and aqueous P. dactylifera pulp extract should be measured to determine the active ingredients that influenced the GIT transit time.

A study by the same group evaluated the protective effects of 3 different extracts of P. dactylifera fruits and seeds against ethanol-induced gastric ulceration in rats [34]. All extracts of P. dactylifera fruit and seeds aqueous, dialyzed or ethanolic were orally administrated in a dose of 4 mL/kg for 14 consecutive days. On the last day rats were given 1 mL of ethanol 80% 1 h before sacrifice. The data revealed marked amelioration of gastric necrosis, hemorrhage, congestion and edema in stomach histological sections and biochemical levels of plasma gastrin and histamine in gastric mucosa induced by ethanol. The authors did not use a positive control group of rats treated with extracts without administration of ethanol, for proper comparison with ethanol treated rats.

Antidiabetic activity

Diabetes mellitus (DM) is one of the common metabolic disorders in which about 2.8% of the worldwide population suffers from DM and its complications. Numerous natural herbs are used as alternatives for treatment of diabetes. The normo-glycemic effect of P. dactylifera may be due to its minerals, phenolics and phytoestrogens constituents. The minerals that are present in P. dactylifera have a vital role in DM management such as magnesium that plays a key role in regulation of insulin action and insulin-mediated-glucose uptake. Zinc induces the insulin formation and release, while chromium potentiates the insulin action, and selenium, which has been shown to stimulate glucose uptake, regulate glycolysis and pentose phosphate pathway. Phenolics present in P. dactylifera are considered to be a potent inhibitor of alpha glycosidase and alpha amylase, leading to reduction of carbohydrates digestion and absorption that may counteract the hyperglycemia present in DM [35].

The antidiabetic effect of P. dactylifera leaves ethanolic extract (PDE) and its organic and aqueous fractions on diabetes induced by alloxan in male rats was investigated by Mard SA, Jalalvand K, Jafarinejad M, Balochi H, Naseri MKG [36]. Freshly prepared solution of alloxan monohydrate in normal saline solution was injected intraperitoneally in a dose of 150 mg/kg to rats that had fasted overnight. After 1 hour, the animals were allowed to feed ad libitum. Their blood glucose level was checked before and 1 week after alloxan injection. The treatment groups received different doses of PDE (100, 200, and 400 mg/kg), PDE fractions (50, 100, and 200 mg/kg), or glibenclamide (4 mg/kg), whereas diabetic control animals received saline (5 mL/kg) orally once a day for 14 days. Blood samples (20 μl) were obtained from the tail tip of fasted rats at 1^st, 6^th, 10^th, and 14^th days, and blood glucose levels were monitored. Oral administration of PDE or its fractions in alloxan-induced diabetic rats significantly reduced blood glucose, serum triacylglycerol and cholesterol when compared with the control group. Plasma insulin levels were increased in the treated groups relative to the control group. This result may be considered as a scientific explanation for the hypoglycemia in alloxan-diabetic rats treated by P. dactylifera.

The antidiabetic effects of aqueous, ethanol, methanol and acetone extracts of different varieties of Omani P. dactylifera seeds were evaluated via an in vitro experiment [37]. All extracts of P. dactylifera seeds of all date varieties possess significant antidiabetic activity, whereas aqueous extract induced the maximum inhibition of α-glucosidase and α- amylase suggesting presence of some non-phenolic water soluble compounds as inhibitors of these enzymes. The inhibitory effect of aqueous extract on α-glucosidase and α- amylase levels may guide the researcher to analyze extracts by HPLC and GC-MS to know the phytochemical constituents that responsible for inhibition of α-glucosidase and α-amylase activities. Inhibition of α-amylase enzyme retards the digestion of starch and glycogen, besides α-glucosidase inhibitors also decrease the digestion of carbohydrates. Hence, P. dactylifera seeds extract reduce the impact of carbohydrates on blood sugar and may be useful along with antidiabetic diets and drugs.

Antihyperlipidemic activity

Hyperlipidemia is the major risk factor for atherosclerosis that leads to morbidity and mortality in Western society; therefore scientists are trying to discover new therapeutics to counteract hyperlipidemia. There are many mechanisms by which herbs can reduce hyperlipidemia through improvements of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity that has a potential role in regulating serum lipid profile. In addition, some herbal extracts induce inhibition of lipid accumulation during adipogenesis or inhibit the lipid production leading lowering serum triacylglycerol, total cholesterol, low-density lipoprotein cholesterol (LDL-C).

A study of the hypolipidemic effect of P. dactylifera leaves (DPL) along with flax seeds (FS) extracts was done in alloxandiabetic rats for 4 weeks [38]. At the 4th week, either FS or DPL extract induced significant decrease in serum total cholesterol levels by 40 and 31% in FS and DPL, respectively. At the 2nd week, serum LDL-C levels were significantly decreased by both extracts, while no significant changes were recognized in serum high density lipoprotein cholesterol (HDL-C) levels. The results suggest that FS and DPL extracts could have hypolipidemic effects in diabetic rats. In order to counteract the diabetic complications, the duration of the experiment should be extended to investigate the effect of both extracts on glycation product such as hemoglobin A1c (HbA1c) and advanced glycation end products. A study of the hypolipidemic mechanism of P. dactylifera would also be useful.

Antimicrobial activity

According to the reports of World Health Organization (WHO), infectious diseases are responsible for over 50% of worldwide deaths, occurring mainly in tropical and developing countries [39]. Many studies have described the traditional use of some medicinal plants in the treatment of some infectious diseases through the antibacterial, antifungal, and antiviral activities of those plants.

In 2000 an in vitro study of the P. dactylifera (Berhi date) aqueous extract on adhesion of Candida species to human buccal epithelial cells (BEC) was done [40]. Amounts of 50, 100 and 200 g of P. dactylifera were suspended in 500 mL sterile distilled water for 24 h, homogenized and filtered. Then, 37 g of brain heart infusion broth was added to each filtrate and the final concentrations were 5, 10 and 20% (w/v). Significant reduction (between 25 % and 52 % in relation to control) in C. albicans, C. tropicalis and C. kefyr adhesion to BEC at the different P. dactylifera aqueous extracts concentrations was observed. The in vivo application of this study on either animals or human would be beneficial for future research.

A study of the Berhi date effect on the cellular ultrastructure of C. albicans was examined by electron microscopy [41]. Weakness and distortion of C. albicans cell wall was seen by scanning electron microscopy when yeast was exposed to 5 % (w/v) P. dactylifera extract. More extensive damage due to cell lysis and concurrent death of C. albicans were noticed at high concentration of P. dactylifera extract (20 %, w/v). Another antimicrobial study of Berhi date extract (20%, w/v) on Bacillus subtilis, Staphylococcus aureus, Salmonella typhi, and Pseudomonas aeruginosa was done by Sallal AK, Ashkenani A [42]. P. dactylifera extract induced about 80 to 99% growth inhibition in nutrient broth cultures of all bacteria. B. subtilis was extensively affected by extract treatment through cell elongation. An application of these results may be that P. dactylifera extract could be included in antimicrobial drugs and in topical ointment manufacture.

Fertility-improvement

Reproduction can be affected by exposure to a wide variety of pollutants, including dioxins, poly-chlorinated biphenyls, heavy metals, chlorination of water, organic solvents and polyaromatic hydrocarbons. Phenolics and flavonoids present in some herbs can induce enhancement of the expression and/or activities of antioxidant enzymes and improve fertility. P. dactylifera pollen is a strong chelator of environmental chemicals especially of heavy metals and their produced ROS, as will be discussed.

Adult male rats were injected intraperitoneally by a single dose of cadmium chloride 1 mg/kg then after 24 hours, rats were treated with ethanolic extract of P. dactylifera pollen (40 mg/kg/day) orally for 56 successive days [43]. Cadmium exposure caused significant reduction in sperm count and motility and with sperm abnormalities along with increased testicular MDA and decreased GSH levels. P. dactylifera pollen (DPP) restored the deleterious effects of cadmium toxicity on spermatogenesis with increase in serum testosterone. The pretreatment of rats by P. dactylifera pollen before cadmium injection should be studied to evaluate the protective potential of P. dactylifera pollen to testis.

Another study was conducted to evaluate the protective effect of DPP ethanolic extract on thyroid disorder-induced testicular dysfunction in male rats. Hyper- and hypothyroidism were induced by intraperitoneal injections of L-thyroxine (300 μg/kg/day) and propylthiouracil (10 mg/kg/day), respectively for 56 days. For the same duration DPP extract was orally administrated in a dose of 150 mg/kg rat. Hyper- and hypothyroidism induced significant lowering in genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone. DPP extract alleviated the reproductive dysfunction in male rats induced either by hyper- or hypothyroidism [44]. In a similar study DPP was administrated orally in doses of 120, 240 and 360 mg DPP/kg rat for 35 days [45]. In comparison to control rats, DPP significantly raised the ratio of testis and epididymis to body weight, sperm count and sperm motility at the of 120 and 240 mg/kg doses. Serum LH and testosterone levels noticeably increased at 120 mg/kg of DPP. Therefore, the above mentioned studies have proven that DPP could improve fertility factors in rats. However, the mechanism by which DPP induces a reproduction improvement in male rats still needs more research in comparison to fertility medications.

A human study was carried out on 69 pregnant women who at 4 weeks prior to their estimated date of delivery ate 6 P. dactylifera fruits per day and were compared with 45 pregnant women as control subjects. In the pregnant women who ate P. dactylifera, there was a significant increase in the mean cervical dilatation (3.52 cm) vs 2.02 cm in the control group, proportion of intact membranes (83% vs 60%, respectively) and spontaneous labor (96% vs 79%, respectively). The women who ate P. dactylifera had a shortened mean latent phase of the first stage of labor by 510 vs 906 minutes for the control group. P. dactylifera at the last 4 weeks of gestation significantly augment labor [46]. These results came in accordance with the heard advising to Mary: “Shake the trunk of the palm tree towards thee: it will drop new, ready dates upon thee. Eat, then, and drink, and let thine eye be cheered!” that may aid you in labor. However, the relationship between P. dactylifera and oxytocin hormone is a research point of interest because oxytocin has a pivotal role in labor, which warrants further investigation.

Conclusion

P. dactylifera possesses numerous curative potentials as antioxidant, anticancer, antidiabetic, antihperlipidemic and antimicrobial along with protection of various cells against different environmental toxic chemicals and side effects of chemotherapy. Most studies relate the pharmacological potentials of P. dactylifera to its antioxidant activity.

The antioxidant activity of P. dactylifera varies according to its varieties and geographical area of cultivation due to variation in phytochemical constituents of P. dactylifera. Therefore, the phytochemical analysis of P. dactylifera fruit, leaves, seeds, pollen, sap and pulp of different extraction solvents has a central role in the protective mechanism of P. dactylifera.

Table 1: A summary of the pharmacological potentials of P. dactylifera.

From the above mentioned data about the therapeutic potentials of P. dactylifera we can recommend some ideas for future research (Table 1).

• Standardize P. dactylifera doses and frequencies in human and animal.

• Study the therapeutic potentials of P. dactylifera fruits, seeds and pollens.

• Describe and characterize P. dactylifera activities and their mechanism of actions.

• Study the protective effect of P. dactylifera against various toxic substances in acute and chronic diseases.

• Study if P. dactylifera make chelation of various toxic substances via in vitro and in GIT

• Study the effect of P. dactylifera on the expressions and activities of free radical generating enzymes.

• Study the metal chelating property of P. dactylifera.

• Study the possible anticancer mechanisms of P. dactylifera in in vitro and in vivo models.

• Evaluate the benefit of P. dactylifera for newly born children.

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