• bioactive secondary metabolites
• date palm
• functional foods and beverages
• plant‐based ingredients
• therapeutic properties

• Phoeniceae/chemistry
• Dietary Supplements/analysis
• Humans
• Phytochemicals/chemistry
• Fruit/chemistry
• Functional Food
• Antioxidants
• Plant Extracts/chemistry
• Plant Extracts/pharmacology

• 20230146 Jordan University of Science and Technology

• Blood glucose
• Dates
• Diabetes mellitus
• Lipid profile
• Microbial contamination

• diabetes
• hypertension
• insulin resistance
• metabolic syndrome (MetS)
• obesity
• phytochemicals

• Humans
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/complications
• Prevalence
• Saudi Arabia/epidemiology
• Insulin Resistance
• Risk Factors
• Obesity/complications
• Obesity/epidemiology
• Diabetes Mellitus

• Anticancer
• Cancer
• Curcumin
• Hepatocellular Carcinoma

• Humans
• Carcinoma, Hepatocellular/drug therapy
• Curcumin/pharmacology
• Curcumin/therapeutic use
• Liver Neoplasms/drug therapy
• Curcuma
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use

• Date seed
• HIIT
• Inflammation
• Muscle damage
• Polyphenol

• Phoenix dactylifera
• cholinergic neurons
• cognitive deficits
• cyclooxygenase-2
• cytokines
• molecular modelling

• date fruit
• hyperglycemia
• hyperlipidemia
• insulin resistance
• tiger nuts
• type-2 diabetes

Phoenix dactylifera L. has a diverse set of pharmacological properties due to its distinct phytochemical profile. The purpose of this study was to investigate the anticancer potential of Phoenix dactylifera seed extract (PDSE) in human breast cancer MDA-MB-231 and MCF-7 cells, as well as liver cancer HepG2 cells, and to investigate the anticancer efficacy in triple-negative MDA-MB-231 cells, followed by in silico validation of the molecular interaction between active components of PDSE and caspase-3, an apoptosis executioner protein .

In this study, human cancer cell lines were cultured and subsequently treated with 10 to 100 μg/mL of PDSE. MTT test was performed to determine the cell viability, MMP was measured using fluorescent probe JC-1, nuclear condensation was determined by Hoechst 33258 dye, Annexin V-FITC & PI staining and cell cycle analysis were evaluated through flow cytometer, and apoptotic markers were detected using western blotting. The bioactive agents in PDSE were identified using high-performance liquid chromatography (HPLC) analysis. The binding affinity was validated using molecular docking tools AutoDock Vina and iGEMDOCK v2.1.

Cell viability data indicated that PDSE inhibited cell proliferation in both breast cancer cells and liver cancer cells. MDA-MB-231 cells showed maximum growth inhibition with an IC₅₀ value of 85.86 μg/mL for PDSE. However, PDSE did not show any significant toxicity against the normal Vero cell line. PDSE induced MMP loss and formation of apoptotic bodies, enhanced late apoptosis at high doses and arrested cells in the S phase of cell cycle. PDSE activated the enzymatic activity of cleaved caspase-3 and caused the cleavage of poly-ADB ribose polymerase (PARP) protein. PDSE upregulated pro-apoptotic Bax protein markedly but  no significant effect on tumor suppressor protein p53, while it downregulated the anti-apoptotic Bcl-2 protein expression. HPLC analysis showed the presence of rutin and quercetin bioactive flavonols in ethanolic extract of PDS. Interestingly, both active components revealed a strong binding interaction with amino acid residues of caspase-3 (PDB ID: 2XYP; Hetero 4-mer - A2B2) protein.

PDS could serve as a potential medicinal source for apoptotic cell death in human breast cancer cells and, thus, could be used as a promising and crucial candidate in anticancer drug development. This study warrants further in vivo research, followed by clinical investigation.

The online version contains supplementary material available at 10.1186/s12906-022-03533-0.

• Cytotoxicity
• HPLC
• Human breast cancer
• Molecular docking
• Phoenix dactylifera seed extract
• Phytoconstituents

The aim of the current study is to investigate the antioxidant and apoptotic potential of Ajwa date flesh (ADF) and Ajwa date pit (ADP) extract on human squamous cell carcinoma cell line (HSC-2).

ADF and ADP were extracted with a solvent extraction method using hexane, acetone, and ethanol, which were then subjected to antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl (DPPH). HSC-2 cells were then treated with different concentrations of ADF and ADP extract for 24, 48, and 72 hours. MTT assay was performed to assess the antiproliferative effect, and Annexin V-FITC was used for the detection of cellular apoptosis.

Acetone extracts of ADF and ADP had the highest radical scavenging and antioxidant activities followed by the ethanolic extracts, whereas ADP appeared to have significantly higher antioxidant effects than ADF. MTT assay demonstrated that acetone extracts of ADF and ADP were significantly cytotoxic against HSC-2 cells in a dose- and time-dependent manner. The half inhibitory concentration (IC50) of ADF was found to be 8.69 mg/ml at 24 h, and the maximum cell growth inhibition was observed at 50 mg/ml. The IC50 for the ADP was found to be 0.97 mg/ml at 24 h, and the maximum cell growth inhibition was observed at 5 mg/ml. Statistical analysis of the flow cytometry assay showed that the treatment with ADF and ADP extracts had a significant apoptotic effect which occurred in a dose-dependent manner. HSC-2 cells were seen in the late apoptotic stage with higher doses of ADF and ADP extract. ADP extract demonstrated higher apoptotic activity than ADF extract. In addition, combined treatment of ADF and ADP was also performed on HSC-2 cells which demonstrated higher apoptotic activity when compared to the single extract.

Ajwa date fruit has a promising cytotoxic effect by inhibiting the growth and proliferation of OSCC cells and inducing cell death by apoptosis.

• Ajwa seeds
• Bax
• Carbon tetrachloride
• FAS
• Hepatotoxicity
• Rats
• SREBP-1

• Dates fruit
• Fasting plasma glucose
• HbA1c
• Postprandial plasma glucose

• Phoenix dactylifera L.
• carotenoids
• cell culture origin
• in vitro health properties
• nutritional compositions
• phenolics
• seed origin

• Agriculture/methods
• Calcium/analysis
• Carotenoids/analysis
• Dietary Fiber/analysis
• Fruit/chemistry
• Nutritive Value
• Phoeniceae/chemistry
• Seeds/chemistry
• Vitamin A/analysis
• Vitamin E/analysis

• anxiety-depression
• date seeds
• insulin
• lipid peroxidation
• streptozotocin-diabetes

• Animals
• Antioxidants/metabolism
• Antioxidants/pharmacology
• Anxiety/drug therapy
• Anxiety/etiology
• Blood Glucose
• Depression/drug therapy
• Depression/etiology
• Diabetes Mellitus, Experimental/complications
• Diabetes Mellitus, Experimental/drug therapy
• Humans
• Hypoglycemic Agents/pharmacology
• Oxidative Stress
• Plant Extracts/pharmacology
• Rats
• Seeds
• Streptozocin/pharmacology

• antidiabetic plants
• hyperglycemia
• natural products
• plant extracts

• Animals
• Diabetes Mellitus/drug therapy
• Humans
• Hypoglycemic Agents/pharmacology
• Hypoglycemic Agents/therapeutic use
• Medicine, Traditional
• Middle East
• Plants, Medicinal/chemistry

• Cytokines
• Date palm (Phoenix dactylifera L.)
• Diabetes mellitus
• Endocrine disruption
• Histopathology
• Immunohistochemistry

• Animals
• Antioxidants
• Apoptosis
• Blood Glucose
• Cytokines
• Diabetes Mellitus, Experimental/drug therapy
• Oxidative Stress
• Phoeniceae
• Plant Extracts
• Rats
• Streptozocin

Diabetes is a chronic metabolic disorder triggered by disturbances in carbohydrate, protein, and lipid metabolisms, where either reduced secretion or sensitivity of insulin is observed coupled with poor glucose control. Date palm fruits are one of the fruits reported to have good potential in diabetes treatment due to its presence of polyphenols exerting strong antioxidant activities. Other possible mechanisms of action include the polyphenolic compounds, which can inhibit enzymes like α-amylase and α-glucosidase. Flavonoids in dates can stimulate β-cells by increasing the number of islets and β-cells, recovering endocrine pancreatic tissues, reducing β-cell apoptosis, activating insulin receptors following the increase in insulin secretion, in addition to improving diabetes-induced complications. In this review, the in vitro, in vivo, and human study-based evidence of date palm as an anti-diabetic fruit is summarised.

• Phoenix dactylifera
• anti-diabetic
• date palm
• dates
• diabetes
• flavonoids
• polyphenols

• 3T3-L1 Cell
• Adipocyte Differentiation
• Adipogenesis
• Glucose Homeostasis
• Obesity
• Phoenix Dactylifera Seed

Full-fat roasted date seeds are considered an excellent source of antioxidants which can treat many diseases. The specific objectives were to investigate the effect of roasting temperature and time on the hardness of whole seeds, moisture content of the roasted date seeds powder, DPPH radical scavenging activity, total phenolic contents, extraction yield, pH, browning index and sensory properties of the brew prepared from the full-fat roasted date seeds and to construct descriptive models that could describe this effect. Date seeds were roasted at three temperatures (160, 180 and 200 °C) for different period of times (10, 20 and 30 min) using a natural conventional oven; then grinded and next brewed. Hardness of whole seeds, moisture content of the seeds powder, DPPH radical scavenging activity and total phenolic contents, extraction yield, pH and browning index and sensory properties of the brew were significantly affected by the roasting conditions. The statistical results indicated that the proposed model could adequately describe the measured properties. Strong correlations have been found among the properties of the brew as well. The producers of the date seeds brew can utilize these results for controlling the roasting process.

• brew
• modelling
• palm date
• roasting process
• seeds

Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosis-inducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide β-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose- and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer.

Ionizing radiation has cytotoxic and genotoxic effects caused mainly by the oxidative damage induced by free radical release. The need for radioprotectives is increasing to protect normal tissues during radiotherapy. In the present study, we investigated the radioprotective effect of Date syrup in rats subjected to whole body radiation at 6 Gy through biochemical, molecular and histopathological analysis. Significant elevations were recorded in the activities of serum ALT, AST, ALP and LDH and in the levels of all lipid profiles parameters, while the level of HDL-C was reduced. The concentration of liver MDA was elevated with depletion of hepatic glutathione (GSH) and catalase. DNA damage was evidenced by increased DNA strand breakage and DNA-protein crosslinks. Significant elevations were observed in the expression of liver TNF-α and serum activity of matrix metalloproteinase (MMP-9). Pretreatment of rats with Date syrup ameliorated the tissue damage induced by radiation as evidenced by the improvement of liver function, antioxidant status and reduction of DNA damage. Besides, liver TNF-α expression and serum MMP-9 activity were reduced. In conclusion, Date syrup could alleviate the toxic effects of ionizing radiation and thus is useful as a radioprotective in radiotherapy regimen.

• Ailments
• anticancer
• bioactive
• dietary
• nutrition
• pharmacological

Phoenix dacylifera is an ancient palm species rich in (poly)phenols. These phenolic compounds were tentatively identified by using liquid chromatography coupled with ion spray mass spectrometry in tandem mode (LC/MS/MS) with negative ion detection. Negative identification of the compounds was based on their retention times and mass spectra in full scan mode (MS), and in different MS/MS modes. For the first time, complete hypothesis, and routs for both p-coumaroylshikimic acids (CoSA) and caffeoylshikimic acids (CSA) were suggested and confirmed by Density Fonctional Theory (DFT) study. Notably, of the 53 compounds characterized, 19 hydroxycinnamates derivatives were tentativelycharacterized in male flowers of date palm and 15 of them were recorded for the first time. In addition, five organic acids, six B-type proanthocyanidins, two anthocyanidin and 21 flavonoid derivatives have been tentatively characterized. Identification of B-type proanthocyanidins were based on the diagnostic ions resulting from heterocyclic ring fission (HRF) and retro-Diels-Alder (RDA) reaction of flavan-3-ol provided information on the hydroxylation pattern and the type of inter-flavan bond proanthocyanidins. The sequence of proanthocyanidins was detected through ions extracted from quinone methide (QM) cleavage of the inter-flavan bond.

• Density Fonctional Theory (DFT)
• Phoenix dactylifera
• caffeoylshikimic acids
• electrospray ionization
• mass spectrometry
• p-coumaroylshikimic acids