Immunostimulant effect of dates (Phoenix dactylifera) on humoral and cellular immunity cells and their functions.

The study aimed to assess the immunomodulatory effects of Phoenix dactylifera (dates) fruit, a traditional remedy used by Moroccans to enhance immunity against pathogens. This research sought to evaluate the impacts of this fruit on immune cells and their functions. To achieve this, we conducted tests using date extracts on splenocytes, thymocytes, and macrophages, focusing on their functions: antibody production, phagocytosis, and T-lymphocyte toxicity. The results obtained demonstrated that the aqueous extract of P. dactylifera fruit exhibited significant immunostimulatory effects on humoral immunity. It achieved this by enhancing complement activity and increasing splenocyte (including B-lymphocytes) proliferation by 142.5% compared to control cells. Similarly, in the same conditions, there was notable stimulation of cellular immunity through thymocyte activity, resulting in a remarkable increase in cell proliferation (225%) and a boost in thymocyte function (245.9%), which plays a role in safeguarding against cancer. Moreover, the date extract demonstrated anti-inflammatory properties. This was evident in the increased phagocytosis activity mediated by macrophages under the ethyl acetate extract, effectively eliminating pathogens. Assessing the cosmetic potential of date extracts showed that the ethyl acetate extract possesses both anti-inflammatory and strong antioxidant effects, exhibited high photo absorption of ultraviolet-B rays. Based on these findings, we propose to study the utilization of this extract for sun protection as a sunscreen. Furthermore, the Fourier-transform infrared spectroscopy analysis indicated that the most active compounds present were flavonoids. These outcomes substantiate the traditional usage of this fruit for reinforcing immunity.

Systematic study on date palm seeds (Phoenix dactylifera L.) extraction optimisation using natural deep eutectic solvents and ultrasound technique.

Natural deep eutectic solvents (NADES) are emerging, environment-friendly solvents that have garnered attention for their application in extracting phenolic compounds. This study investigated the effects of four synthetic NADES on polyphenols extracted from date seeds (DS) using choline chloride (ChCl) as a hydrogen-bond acceptor and lactic acid (La), citric acid (Citri), glycerol (Gly), and fructose (Fruc) as hydrogen-bond donors, in comparison with DS extracts extracted by conventional solvents (water, 70% methanol, and 70% ethanol). The antioxidant activity (DPPH), total phenolic content (TPC) and 6 phenolic compounds were determined using HPLC. The results showed that the ChCl-La and ChCl-Citri systems exhibited a high extraction efficiency regarding TPC, and DPPH in the DS extracts extracted by NADES compare to those DS extracts extracted with conventional solvents (p ˂ 0.001). HPLC results demonstrated that DS extracted by ChCl-La contained all measured phenolic compounds. Also gallic acid and catechin were the major compounds identified in the DS extracts. In addition DS extracted by ChCl-Citri and ChCl-Gly had the highest concentration of catechin. In conclusion, combining NADES is a promising and environment-friendly alternative to the conventional solvent extraction of phenolic compounds from DS.

Cytotoxic Effect of Phoenix dactylifera (Iraqi Date) Leaves and Fruits Extracts against Breast Cancers Cell Lines.

OBJECTIVE: Now a day's cancerous diseases are the most prevalent life threatening that spreading because of the lifestyle. Its due to uncontrolled growth of cell which can be cured if diagnosed in early stage. Treatment of cancer depends on the various internal and external factors causing cancer. The main objective of this study is using herbal based medicine to manage breast cancer, the second most common type of cancer in the world. METHODS: In this study, the anticancer effect of two Iraqi date palm part extracts (leaves and fruits) against panel of breast cancer cell lines (AMJ13و MCF7, MDA-MB-231, CAL51) in vitro to evaluate their possible antitumor effect and their safety on normal cell line (MEF). RESULTS: The Phoenix dactylifera (dray Zahdi) fresh leave extract showed highly cytotoxic effects in all breast cancer cell lines. The leaves extract was showed concentration dependent cytotoxicity effects after 72 h exposure time. Leave extracts was effective against AMJ13 cell line. The effective concentrations in both cancer cells ranged from 2500-20000 µg/ ml with inhibition percentage against AMJ13 was (66.7, 70.6, 53, and 54%). While the effect against MCF7, MDA-MB, and CAL51 cell lines were less with significant effect only at two concentrations (10000- 20000 µg/ ml) causing 64.3, and 64.3% growth inhibition respectively in MCF7, and 40, and 50% respectively in MDA-MB, and 44.0, and 52.0% respectively in CAL51. The dray date fruit extract has no significant cytotoxicity against all the cancer cells. Both extracts have no effect against normal fibroblast cells. CONCLUSION: In conclusion, Phoenix dactylifera fresh leave extract shows promising anticancer properties while the fruit extract has no direct anticancer effect.

Determination and health risk assessment of carbamate pesticide residues in date palm fruits (Phoenix dactylifera) using QuEChERS method and UHPLC-MS/MS.

This study aimed to investigate carbamate pesticide residues in different varieties of date palm fruits in the UAE, utilizing UHPLC-MS/MS. For sample preparation and clean-up, the efficiency and performance of different QuEChERS dispersive solid-phase extraction kits were compared. Precision and recovery were assessed at 10 µg kg-1 for the three kits, revealing that Kit 2 demonstrated the best performance. The selected QuEChERS method was validated to detect 14 carbamate residues in 55 date samples. The method exhibited strong linearity with R2 > 0.999 and low LOD (0.01-0.005 µg kg-1) and LOQ (0.003-0.04 µg kg-1). Excellent accuracy (recovery: 88-106%) and precision (RSD: 1-11%) were observed, with negligible matrix effect (- 4.98-13.26%). All samples contained at least one carbamate residue. While most detected residues were below their MRLs, carbosulfan was found in 21 samples, propoxur in 2 samples, and carbofuran in 1 sample above their MRLs. The hazard index (HI) was calculated for carbosulfan, phenmedipham, carbaryl, propoxur, carbofuran, and methomyl to assess potential health risks for date consumers. All HI values were below the safety limit of 1.0, indicating that the consumption of dates does not pose a non-carcinogenic health risk for adults and children.

Anti-inflammatory and anti-rheumatic effects of Phoenix dactylifera L. (date palm) seed by controlling cytokines and inhibiting JAK1/STAT3 pathway on CFA-induced arthritis rat and its phytochemical profiling.

ETHNOPHARMACOLOGICAL RELEVANCE: Phoenix dactylifera L. (date palm) seed is widely used in Arabian traditional medicine to alleviate several health problems including inflammatory conditions. The herbal tea of date palm seed has been consumed by rheumatoid patients to relief their symptoms. AIM OF THE STUDY: The purpose of this study was to investigate the claimed beneficial use of P. dactylifera L. (Sewy variety) seed (PDS) in the treatment of rheumatoid arthritis (RA) and its mechanism of action as well as to study its phytoconstituents. MATERIALS AND METHODS: The anti-inflammatory and anti-oxidative properties of the non-polar and the polar extracts of PDS were studied using Complete Freund's adjuvant (CFA)-induced arthritis rat model. Paw edema, body weight, total nitrate/nitrite NOX content and cytokine markers were evaluated to monitor the progress of arthritis. Also, histological examination and thermal analysis were conducted. The phytoconstituent profiles of non-polar and polar extracts of PDS were investigated using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). The multiple reactions monitoring mode (MRM) of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was used to quantify phenolic phytoconstituents in both extracts. RESULTS: According to the findings, the polar and non-polar PDS extracts kept body weight comparable to those of healthy individuals while considerably lowering paw swelling, edema, and neutrophil infiltration. It also reduced the levels of Nuclear Factor Kappa B (NF-κB), Tumor Necrosis Factor Alpha (TNF-α), Interleukin 22, Interleukin 23, Interferon (IFN), Interleukin 17, Interleukin 1ß, Interleukin 6, Interleukin 36, Janus Kinase 1 (JAK1), and Signal Transducer and Activator of Transcription 3 (STAT3). They also reduced the degenerative alterations caused by RA. Thermal research gave additional support for these findings. 83 phytoconstituents were identified in the non-polar PDS extract and 86 phytoconstituents were identified in the polar PDS extract. 74 of the identified phytoconstituents were common in both extracts. 33 phytoconstituents were identified here from P. dactylifera for the first time as far as we know. In MRM-LC-ESI-MS/MS analysis, the major phenolics in both extracts were chlorogenic acid, naringenin, and vanillin. Catechin was only detected in the non-polar PDS extract. On the other hand, apigenin, kaempferol, and hesperetin were only detected in the polar PDS extract. Generally, the polar PDS extract showed higher concentrations of the identified phenolics than the non-polar extract. CONCLUSIONS: The PDS extracts especially the non-polar extract showed significant anti-inflammatory and anti-oxidative properties in the CFA-induced arthritis rat model. PDS might be used to produce RA medicines.

Phoenix dactylifera L.: An Overview of Phytochemical Constituents and Impact on Women's Health.

Phoenix dactylifera L. (date palm) is the most significant member of the palm family (Arecaceae), particularly in the Middle East and Arab World. It is a valuable source of both primary and secondary metabolites including sugars, amino acids, phenolic acids, flavonoids, proanthocyanidins, carotenoids, phytosterols, terpenes and sphingolipids, besides vitamins and minerals. Besides, it possesses a wide array of pharmacologic activities viz. immunomodulatory, antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, anti-mutagenic and anti-cancer activities, in addition to its positive effects on male and female fertility. Further research is still required to deeply understand its clinical implications, especially concerning women's health. Moreover, there are other Phoenix species that still need to be investigated to learn more about their undiscovered phytochemical components and biological activities.

Anticancer Properties of Different Varieties of Date Palm (Phoenix dactylifera L.) Leaf Extracts in Human Tumor Cells: a Comparative Study.

Plant polyphenols are nutraceutical components with relevant biological effects on human health. They act against development of several diseases including cancer. In this study, the methanolic extracts of four date palm Phoenix dactylifera leaves (Deglet Noor (DN), Barhee (B), Khalas (KS) and Khunezi (KZ)) collected from south Tunisia were preliminary analyzed for their effects against U87 (human glioblastoma) and MDA-MB-231 (human breast cancer) cell line development. Results showed that Barhee extract (30 µg/mL) was the most efficient to reduce the growth of both tumor cells to about 40% (p < 0.05) without inducing cytotoxicity. Significantly, KS, KZ, DN and B extracts (30 µg/mL) decreased MDA-MB-231 and U87 cell adhesion towards fibrinogen and fibronectin. Using integrin blocking antibodies, leaf extracts competitively decreased human glioblastoma cell attachment to immobilized antibodies by interfering to αvß3 and α5ß1 integrin receptors. At the same concentration, extracts decreased MDA-MB-23 and U87 cell migration performed with wound healing assay. Particularly, Barhee and Deglet Noor leaf extracts (30 µg/mL) significantly reduced U87 cell invasion by 52.92% (p < 0.01) and 74.56% (p < 0.01), respectively. Collegially, our findings revealed beneficial proprieties of four varieties of date palm leaf especially those displayed by DN and B extracts that may serve as active candidates against human glioblastoma and breast cancer progression.

Antioxidant, LC-MS Analysis, and Cholinesterase Inhibitory Potentials of Phoenix dactylifera Cultivar Khudari: An In Vitro Enzyme Kinetics and In Silico Study.

We evaluated the therapeutic potentials of Khudari fruit pulp, a functional food and cultivar of Phoenix dactylifera, against neurological disorders. Our results demonstrate a good amount of phytochemicals (total phenolic content: 17.77 ± 8.21 µg GA/mg extract) with a high antioxidant potential of aqueous extract (DPPH assay IC50 = 235.84 ± 11.65 µg/mL) and FRAP value: 331.81 ± 4.56 µmol. Furthermore, the aqueous extract showed the marked inhibition of cell-free acetylcholinesterase (electric eel) with an IC50 value of 48.25 ± 2.04 µg/mL, and an enzyme inhibition kinetics study revealed that it exhibits mixed inhibition. Thereafter, we listed the 18 best-matched phytochemical compounds present in aqueous extract through LC/MS analysis. The computational study revealed that five out of eighteen predicted compounds can cross the BBB and exert considerable aqueous solubility. where 2-{5-[(1E)-3-methylbuta-1,3-dien-1-yl]-1H-indol-3-yl}ethanol (MDIE) indicates an acceptable LD50. value. A molecular docking study exhibited that the compounds occupied the key residues of acetylcholinesterase with ΔG range between -6.91 and -9.49 kcal/mol, where MDIE has ∆G: -8.67 kcal/mol, which was better than that of tacrine, ∆G: -8.25 kcal/mol. Molecular dynamics analyses of 100 ns supported the stability of the protein-ligand complexes analyzed through RMSD, RMSF, Rg, and SASA parameters. TRP_84 and GLY_442 are the most critical hydrophobic contacts for the complex, although GLU_199 is important for H-bonds. Prime/MM-GBSA showed that the protein-ligand complex formed a stable confirmation. These findings suggest that the aqueous extract of Khudari fruit pulp has significant antioxidant and acetylcholinesterase inhibition potentials, and its compound, MDIE, forms stably with confirmation with the target protein, though this fruit of Khudari dates can be a better functional food for the treatment of Alzheimer's disease. Further investigations are needed to fully understand the therapeutic role of this plant-based compound via in vivo study.

Phytochemical-derived tumor-associated macrophage remodeling strategy using Phoenix dactylifera L. boosted photodynamic therapy in melanoma via H19/iNOS/PD-L1 axis.

BACKGROUND: The tumor microenvironment (TME) represents a barrier to PDT efficacy among melanoma patients. The aim of this study is to employ a novel muti-tactic TME-remodeling strategy via repolarization of tumor-associated macrophages (TAMs), the main TME immune cells in melanoma, from the pro-tumor M2 into the antitumor M1 phenotype using Phoenix dactylifera L. (date palm) in combination with PDT. METHODS: Screening of different date cultivars was employed to choose extracts of selective toxicity to melanoma and TAMs, not normal macrophages. Potential extracts were then fractionated and characterized by gas chromatography-mass spectrometry (GC-MS). Finally, the efficacy and the potential molecular mechanism of the co-treatment were portrayed via quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: Initial screening resulted in the selection of the two Phoenix dactylifera L. cultivars Safawi and Sukkari methanolic extracts. Sukkari showed superior capacity to revert TAM phenotype into M1 as well as more prominent upregulation of M1 markers and repression of melanoma immunosuppressive markers relative to positive control (resiquimod). Molecularly, it was shown that PDT of melanoma cells in the presence of the secretome of repolarized TAMs surpassed the monotherapy via the modulation of the H19/iNOS/PD-L1immune-regulatory axis. CONCLUSION: This study highlights the potential utilization of nutraceuticals in combination with PDT in the treatment of melanoma to provide a dual activity through alleviating the immune suppressive TME and potentiating the anti-tumor responses.

Phoenix dactylifera (Ajwa Dates) Alleviate LPS-Induced Sickness Behaviour in Rats by Attenuating Proinflammatory Cytokines and Oxidative Stress in the Brain.

Traditional medicine claims that various components of the Phoenix dactylifera (date plant) can be used to treat memory loss, fever, inflammation, loss of consciousness, and nerve disorders. The present study aims to evaluate the effectiveness of Phoenix dactylifera fruit extracts (PDF) against rat sickness behaviour caused by lipopolysaccharide (LPS) by assessing behavioural and biochemical parameters. PDF was prepared by extracting dry fruits of P. dactylifera with a methanol:water (4:1, v/v) mixture. The PDF was evaluated for phenolic and flavonoid content and HPLC analysis of quercetin estimation. Adult Wistar rats were treated with LPS, PDF + LPS and dexamethasone + LPS. Water and food intake, behavioural tests such as locomotor activity, tail suspension and forced swim tests were conducted. Furthermore, alanine transaminase (ALT) and aspartate transaminase (AST) were estimated in plasma and malondialdehyde (MDA), reduced glutathione (GSH), nitrite, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were estimated in the brain. PDF ameliorated LPS-induced sickness behaviour by reducing MDA, nitrite, IL-6, and TNF-α levels and improving GSH, behavioural alteration, water and food intake in the treated rats. In the plasma of the treated rats, PDF also decreased the levels of ALT and AST. The outcomes demonstrated the efficacy of PDF in reducing the sickness behaviour caused by LPS in rats. The authors believe that this study will provide the groundwork for future research to better understand the underlying mechanisms of action and therapeutic efficacy.

Promising anti-Helicobacter pylori and anti-inflammatory metabolites from unused parts of Phoenix dactylifera CV 'Zaghloul': in vitro and in silico study.

CONTEXT: Date palm waste is an agricultural waste that accumulates in massive amounts causing serious pollution and environmental problems. OBJECTIVES: Date palm trees, Phoenix dactylifera Linn CV 'Zaghloul' (Arecaceae) grown in Egypt, leave behind waste products that were investigated to produce compounds with anti-Helicobacter pylori and anti-inflammatory activities. MATERIALS AND METHODS: Chromatographic workup of P. dactylifera aqueous methanol extract derived from fibrous mesh and fruit bunch (without fruit) afforded a new sesquiterpene lactone derivative, phodactolide A (1), along with ten known compounds (2-11), primarily identified as polyphenols. Chemical structures were unambiguously elucidated based on mass and 1D/2D NMR spectroscopy. All isolated compounds were assessed for their activities against H. pylori using broth micro-well dilution method and clarithromycin as a positive control. The anti-inflammatory response of isolated compounds was evaluated by inhibiting cyclooxygenase-2 enzyme using TMPD Assay followed by an in silico study to validate their mechanism of action using celecoxib as a standard drug. RESULTS: Compounds 4, 6 and 8-10 exhibited potent anti-H. pylori activity with MIC values ranging from 0.48 to 1.95 µg/mL that were comparable to or more potent than clarithromycin. For COX-2 inhibitory assay, 4, 7 and 8 revealed promising activities with IC50 values of 1.04, 0.65 and 0.45 µg/mL, respectively. These results were verified by molecular docking studies, where 4, 7 and 8 showed the best interactions with key amino acid residues of COX-2 active site. CONCLUSION: The present study characterizes a new sesquiterpene lactone and recommends 4 and 8 for future in vivo studies as plausible anti-ulcer remedies.

The anti-toxic effect of the date palm fruit extract loaded on chitosan nanoparticles against CCl4-induced liver fibrosis in a mouse model.

The liver is the most important organ in the body. Hepatocyte oxidative damage occurs to excess ROS. Liver fibrosis is a mechanism that the immune system uses to treat extreme inflammation by repairing damaged tissue with the creation of a scar. The outcome of fibrosis may be reversed by consuming natural plant extracts with high ROS-scavenging ability. The date palm fruits contain caffeic acid, gallic acid, syringic acid, and ferulic acid, which have anti-inflammatory, antioxidant, and hepatoprotective properties. This study aimed to prepare a date fruit extract, load it onto chitosan nanoparticles, and compare its anti-fibrotic activity with the unloaded crude extract in the CCl4-mouse model. Our findings show that nanocomposite (Cs@FA/DEx) has anti-fibrotic properties and can improve liver function enzymes and endogenous antioxidant enzymes by inhibiting cell apoptosis caused by CCl4-induction in mice. Furthermore, significantly reduced CD95 and ICAM1 levels and down-regulation of TGFß-1 and collagen-α-1 expression demonstrated the anti-fibrotic effects of the Cs@FA/DEx. Therefore, the Cs@FA/DEx might be an innovative supplement for inhibiting liver fibrosis and hepatocyte inflammation induced by chemical toxins. Besides, this nano-supplement could be a promising anti-hepatocellular carcinoma agent as it has potent in vitro anticancer activity against the HePG2 cell line.

Antioxidant, Tyrosinase, α-Glucosidase, and Elastase Enzyme Inhibition Activities of Optimized Unripe Ajwa Date Pulp (Phoenix dactylifera) Extracts by Response Surface Methodology.

The Ajwa date (Phoenix dactylifera L., Arecaceae family) is a popular edible fruit consumed all over the world. The profiling of the polyphenolic compounds of optimized unripe Ajwa date pulp (URADP) extracts is scarce. The aim of this study was to extract polyphenols from URADP as effectively as possible by using response surface methodology (RSM). A central composite design (CCD) was used to optimize the extraction conditions with respect to ethanol concentration, extraction time, and temperature and to achieve the maximum amount of polyphenolic compounds. High-resolution mass spectrometry was used to identify the URADP's polyphenolic compounds. The DPPH-, ABTS-radical scavenging, α-glucosidase, elastase and tyrosinase enzyme inhibition of optimized extracts of URADP was also evaluated. According to RSM, the highest amounts of TPC (24.25 ± 1.02 mgGAE/g) and TFC (23.98 ± 0.65 mgCAE/g) were obtained at 52% ethanol, 81 min time, and 63 °C. Seventy (70) secondary metabolites, including phenolic, flavonoids, fatty acids, and sugar, were discovered using high-resolution mass spectrometry. In addition, twelve (12) new phytoconstituents were identified for the first time in this plant. Optimized URADP extract showed inhibition of DPPH-radical (IC50 = 87.56 mg/mL), ABTS-radical (IC50 = 172.36 mg/mL), α-glucosidase (IC50 = 221.59 mg/mL), elastase (IC50 = 372.25 mg/mL) and tyrosinase (IC50 = 59.53 mg/mL) enzymes. The results revealed a significant amount of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.

Effects of Phoenix dactylifera against Streptozotocin-Aluminium Chloride Induced Alzheimer's Rats and Their In Silico Study.

Phoenix dactylifera is known for medicinal importance due to its antioxidant, antidiabetic, antidepressant, and anti-inflammatory properties. This study is aimed at evaluating the effect of P. dactylifera seeds to cure Alzheimer's disease (AD). AD was induced in the rats with streptozotocin + aluminium chloride followed by treatment of methanolic extract of P. dactylifera seeds. The blood glucose levels were determined at regular intervals, which showed a prominent decrease in the extracts treated group. Behavior tests, including the Elevated Plus Maze (EPM) test and Morris Water Maze (MWM) test, were used to evaluate memory patterns in rats. The results indicated that extract-treated rats significantly improved memory behavior compared to the diseased group. After dissection, the serum electrolytes, antioxidant enzymes, and choline esterase enzymes were measured in different organs. The serum parameters creatinine, urea, and bilirubin increased after extract treatment. Similarly, the level of antioxidant enzymes like peroxidases (POD), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and thiobarbituric acid reactive substance (TBARS) in the extract-treated group showed improved results that were close to the normal control group. The enzyme (lipase, insulin, amylase, and acetylcholine) levels were found enhanced in extract groups as compared to diseased rats. High-performance liquid chromatography (HPLC) was used to determine the level of dopamine and serotonin neurotransmitters, which were increased significantly for P. dactylifera seeds with values of 0.18 µg/mg tissue and 0.56 µg/mg tissue, respectively. Overall, results showed that P. dactylifera seeds proved to be quite efficient in improving the memory and behavior of treated rats. The antioxidants and enzymes were also increased; therefore, it may be a potential candidate for treating AD.

Chemical Profile of the Pits Oil from the Tunisian 'Alig' Cultivar of Phoenix dactylifera L.: In Vivo Wound Healing Potential Evaluation of a Cream Formulated from the Extracted Oil and Insights from Molecular Docking and SAR Analysis.

Since ancient times the oil from date palm pits (Phoenix dactylifera L.) has been used to heal wounds. In order to prove this traditional usage of the pits, this oil was extracted from the pits of the Tunisian cultivar 'Alig' and its physico-chemical properties and the chemical composition were evaluated. The fatty acid profile, evidenced by GC, allowed to classify this oil as an oleic-myristic acid oil with a clear abundance of oleic acid (53.66 %). 1 H and 13 C-NMR as well as FT-IR analyses confirmed the presence of fatty acids in triglyceride forms. Furthermore, in vivo wound healing activity of a cream formulated from the extracted oil was performed, for the first time, using a rat model and was compared to placebo cream and a commercial formulation, MEBO®. This study showed that the test cream promoted the healing of pressure ulcers better than the placebo cream and the MEBO® ointment. The results showed that this vegetable oil is able to improve the healing of infected wounds in rats, thus supporting its traditional use. The contribution of the main oleic, linoleic and myristic acids that can be derived from enzymatic hydrolysis to the healing activity of the whole pits oil was predicted by in silico study and the calculated pharmacokinetics parameters.

Biochemical Composition and Biological Activities of Date Palm (Phoenix dactylifera L.) Seeds: A Review.

Date palm (Phoenix dactylifera L.) is an essential agricultural crop in most Middle Eastern countries, and its fruit, known as dates, is consumed by millions of people. Date seeds, a by-product of the date fruit processing industry, are a waste product used as food for domestic farm animals. Date seeds contain abundant sources of carbohydrates, oil, dietary fiber, and protein; they also contain bioactive phenolic compounds that may possess potential biological properties. In addition, its rich chemical composition makes date seeds suitable for use in food product formulation, cosmetics, and medicinal supplements. This review aims to provide a discourse on the nutritional value of date seeds. The latest data on the cytotoxicity of date seed compounds against cancer cell lines, its ability to combat diabetes, antioxidant potential, antimicrobial effect, and anti-inflammatory activity will be provided, considering its potential to be a nutritional therapeutic agent for chronic diseases. Application of date seeds in the form of powder and oil will also be discussed.

Barhi date (Phoenix dactylifera) extract ameliorates hepatocellular carcinoma in male rats.

Hepatocellular carcinoma (HCC) is a malignant tumor with limited treatment options. Given this fact, it may be important to develop new molecular targeted therapies from natural products, especially those which are primary sources of effective anticancer drugs with distinct mechanisms. Moreover, the complementary use of traditional herbs or fruit may increase the possibility of finding curative options for cancer. Here we explore the anticancer effects and possible molecular mechanism of Barhi date extract using an HCC rat model. Thirty two male albino rats were arbitrarily allocated into four groups: a negative control group (NCG); a positive control group (PCG), which received CCl4 (1 ml/kg b.wt./ i.p.) twice a week for three months; a Barhi date extract (400 mg/kg b.wt./day/orally) treatment group (DTG) during the third month of CCl4 administration; and a cisplatin (1.5 mg/kg b.wt./ i.p.) treatment group ( CTG) during the third month of CCl4 administration. After treatment we performed biochemical analyses of all groups to assess relative eukaryotic initiation factor 2 alpha (eIF2α), extracellular signal-regulated kinases (ERKs), protein kinase RNA-like endoplasmic reticulum kinase (PERK), poly (ADP-ribose) polymerase (PARP), and CASPASE 3 protein content, and examined expression of the genes phosphatase and tensin homolog (PTEN) and protein kinase B (AKT). We also performed an immunohistochemistry assay for alpha-fetoprotein (AFP). Our data showed higher PARP and CASPASE3 levels and liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) in the PCG compared to the DTG and the cisplatin treatment group CTG. However, we also found a significant decrease in PTEN in the PCG relative to both the DTG and the CTG. We conclude that the anti-tumor activity of Barhi date extract may be mediated by the inhibition of cell proliferation and apoptosis via the ERK /PARP/caspase3 pathway and the AKT/ PTEN signaling pathways.

Date Palm as Source of Nutraceuticals for Health Promotion: a Review.

PURPOSE OF REVIEW: Chronic diseases are problematic to health professional specially when using drugs throughout the course of life with un-tolerated side effects. Returning to nature through using nutraceuticals might have both protective and therapeutic effects. Date palm was claimed to be a good source of such nutraceuticals or functional food ingredients. The purpose of the present review was to spot light on the different phytochemicals, phytonutrients, and remedial effects of date palm (Phoenix dactylifera L.) in a goal to be utilized in form of nutraceuticals. The possible mechanisms of action of the remedial effects were among the aim of the study. RECENT FINDINGS: A protein hydrolyzate prepared from date seed could prevent DNA mutation and susceptibility to cancer. In addition to cancer prevention, date palm fruit improved the treatment outcome of cancer pediatric patients and possesses anti-angiogenic activity as one of the important anticancer mechanisms of action. On the other hand, date seed extracts was recently reported to protect from ulcerative colitis. It seems that all the aforementioned remedial effect might be ascribed to immunoregulatory effect of date palm. These findings proposed that date palm is beneficial for health. Date palm fruit is a rich source of vitamins, minerals, dietary fibers, energy, and easily digestible and absorbable sugars that instantaneously replenish and revitalize the body specially after fasting condition. Mineral contents in date fruits include potassium, phosphorus, magnesium, and calcium. Diverse health claims were reported to belong to various parts of the tree including the edible part of fruits, the seeds, the leaves, spathe (an envelope-like structure that encloses male and female date palm flowers), and pollen grains due to the presence of different bioactive constituents. The main phytochemicals and phytonutrients reported in date palms are phenolic compounds, carotenoids, sterols, anthocyanins, and others. In folk medicine, date palm fruits are used for enhancing immunity and treating gastrointestinal tract disorders, edema, bronchitis, wound, cancer, as well as infectious diseases. However, the exact health benefits and remedial effects of date palm were not fully and deeply investigated. The present review focused on the bioactive constituents and the reported health benefits of date palm and proposed mechanism of action.

Effect of Raw and Roasted Phoenix dactylifera L. Seed Polyphenols Extracts on Suppression of Angiogenesis in Endothelial Cells.

Date seed is a by-product of Phoenix dactylifera L. fruit which is well recognized for its polyphenols content and numerous health-beneficial effects. Due to the increasing interest in natural phytochemicals with antioxidant activities, the present study aimed to extract polyphenols from both raw and roasted date seeds and investigate the anti-angiogenic effect of these two extracts (raw and roasted date seed polyphenols extracts (DSPE) at 25 and 50 µg/mL) using human microvascular endothelial cells (HMVEC). Our results showed that both raw and roasted DSPE suppressed some angiogenesis features in a dose-dependent manner including cell proliferation, migration, and capillary-like structure formation, of which raw DSPE was more potent inhibitor than roasted DSPE. Reduction in reactive oxygen species, as well as enhancement of superoxide dismutase activity occurred using both raw and roasted date seed polyphenols extracts. However, no changes were observed in advanced oxidation protein products versus control. Taken together, our data indicated that raw and roasted DSPE possess antioxidant activity, which suggested their potential use as a source of polyphenols with anti-angiogenic properties. Nevertheless, further studies are required to explore the underlying mechanisms responsible for their anti-angiogenic activities.

Ultrasound-assisted extraction of highly nutritious date sugar from date palm (Phoenix dactylifera) fruit powder: Parametric optimization and kinetic modeling.

Alternative sweeteners to white sugar with a lower calorie content and glycemic index obtained through date palm fruits is of great interest to the food industry. In this study, ultrasound-assisted extraction of nutritive sugar from date fruit powder was investigated through Box-Behnken design. A maximum total sugar content (TSC) of 812 mg glucose eq./g of DFP was obtained with a sugar extraction yield (SEY) of 81.40 ± 0.27 % under the following optimal extraction conditions: extraction temperature of 60 °C, extraction time of 30 min, and L/S ratio of 7.6 mL/g. Various modern techniques were used to characterize the obtained extracts and associated residues. The results showed that the extract contained fructose, glucose, and sucrose and had good thermal stability. Furthermore, SEM and TSC analysis revealed that ultrasonic treatment of the biomass improved mass transfer diffusion due to acoustic or ultrasonic cavitation, resulting in a higher sugar yield.