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Candidiasis, caused by opportunistic fungal pathogens of the Candida genus, poses a significant threat to immunocompromised individuals. Natural compounds derived from medicinal plants have gained attention as potential sources of anti-fungal agents. Ajwa dates (Phoenix dactylifera L.) have been recognized for their diverse phytochemical composition and therapeutic potential. In this study, we employed a multi-faceted approach to explore the anti-candidiasis potential of Ajwa dates' phytochemicals. Utilizing network pharmacology, we constructed an interaction network to elucidate the intricate relationships between Ajwa dates phytoconstituents and the Candida-associated molecular targets of humans. Our analysis revealed key nodes in the network (STAT3, IL-2, PTPRC, STAT1, CASP1, ALB, TP53, TLR4, TNF and PPARG), suggesting the potential modulation of several crucial processes (the regulation of the response to a cytokine stimulus, regulation of the inflammatory response, positive regulation of cytokine production, cellular response to external stimulus, etc.) and fungal pathways (Th17 cell differentiation, the Toll-like receptor signaling pathway, the C-type lectin receptor signaling pathway and necroptosis). To validate these findings, molecular docking studies were conducted, revealing the binding affinities of the phytochemicals towards selected Candida protein targets of humans (ALB-rutin (-9.7 kJ/mol), STAT1-rutin (-9.2 kJ/mol), STAT3-isoquercetin (-8.7 kJ/mol), IL2-ß-carotene (-8.5 kJ/mol), CASP1-ß-carotene (-8.2 kJ/mol), TP53-isoquercetin (-8.8 kJ/mol), PPARG-luteolin (-8.3 kJ/mol), TNF-ßcarotene (-7.7 kJ/mol), TLR4-rutin (-7.4 kJ/mol) and PTPRC-rutin (-7.0 kJ/mol)). Furthermore, molecular dynamics simulations of rutin-ALB and rutin-STAT1 complex were performed to gain insights into the stability and dynamics of the identified ligand-target complexes over time. Overall, the results not only contribute to the understanding of the molecular interactions underlying the anti-fungal potential of specific phytochemicals of Ajwa dates in humans but also provide a rational basis for the development of novel therapeutic strategies against candidiasis in humans. This study underscores the significance of network pharmacology, molecular docking and dynamics simulations in accelerating the discovery of natural products as effective anti-fungal agents. However, further experimental validation of the identified compounds is warranted to translate these findings into practical therapeutic applications.
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Thermal burns produce tissue damage, which eliminates the protective role of tissue. Due to the extensive tissue damage from severe burns, an overactive immune response occurs. Furthermore, this raises the possibility of getting sepsis, a condition in which a bacterial infection spreads throughout the body rather than only in the area of the injury or localized infection. To determine the compounds of Ajwa dates have the potential as an anti-inflammatory and antibacterial agent in infectious thermal burns. The research method used the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Various references were collected from the online database Google Scholar and PubMed including reports, journals, and all references mostly published no more than the past 10 years. This systematic review revealed 16 research articles that were pertinent. Polyphenolic substances such as flavonoids, glycosides, and phenolic acids were found in ajwa dates. Specified polyphenol chemicals have the ability to interact with one or more immune cell receptors, moving intracellular messages and influencing the host's immunological response. Ajwa dates' polyphenol acts as an anti-inflammatory agent in severe burns by inhibiting the expression of pathogen-associated molecular pattern receptors, controlling transcription factors, and changing the phenotype of macrophage cells, among other ways. The bacterial activity and immune response regulation of Ajwa dates, on the other hand, also serve as an antibacterial agent directly. The polyphenol compounds in Ajwa dates have the potential to operate as an anti-inflammatory and antibacterial agent in infected thermal burns.
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Objective: To evaluate the effect of Ajwa dates pit powder (ADP) on lipid profile, body composition and blood pressure in patients with hyperlipidemia. Materials and Methods: This randomized controlled clinical study was carried out on 40 patients with total cholesterol >200 mg/dl, triglycerides >150 mg/dl and BMI >25, of either sex, aged 30-50 years, who were recruited through written consent. The patients were divided into two groups (n=20 each): the ADP and the control group (CG). All patients received the doctor's prescribed class A statin (Rosuvastatin/ Atorvastatin) 10 mg/day, while 2.7 g ADP was given on daily basis before breakfast with lukewarm water for 40 days and the control group received the same amount of wheat flour. Body composition, blood pressure and lipid profile were determined at baseline, and after 20 and 40 days. Data were analyzed by using SPSS and GraphPad Prism. Results: ADP significantly reduced body weight (p<0.001), BMI (p<0.001), fat mass, body fat percentage, visceral fat area and waist circumference compared to the control group. Similarly, ADP significantly (p=0.000) decreased the serum level of total cholesterol and low-density lipoprotein. Conclusion: ADP may have the potential to improve dyslipidemia and obesity.
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The date palm (Phoenix dactylifera L.) is a popular edible fruit consumed all over the world and thought to cure several chronic diseases and afflictions. The profiling of the secondary metabolites of optimized ripe Ajwa date pulp (RADP) extracts is scarce. The aim of this study was to optimize the heat extraction (HE) of ripe Ajwa date pulp using response surface methodology (RSM) and artificial neural network (ANN) modeling to increase its polyphenolic content and antioxidant activity. A central composite design was used to optimize HE to achieve the maximum polyphenolic compounds and antioxidant activity of target responses as a function of ethanol concentration, extraction time, and extraction temperature. From RSM estimates, 75.00% ethanol and 3.7 h (extraction time), and 67 °C (extraction temperature) were the optimum conditions for generating total phenolic content (4.49 ± 1.02 mgGAE/g), total flavonoid content (3.31 ± 0.65 mgCAE/g), 2,2-diphenyl-1-picrylhydrazyl (11.10 ± 0.78 % of inhibition), and cupric-reducing antioxidant capacity (1.43 µM ascorbic acid equivalent). The good performance of the ANN was validated using statistical metrics. Seventy-one secondary metabolites, including thirteen new bioactive chemicals (hebitol II, 1,2-di-(syringoyl)-hexoside, naringin dihydrochalcone, erythron-guaiacylglycerol-ß-syringaresinol ether hexoside, erythron-1-(4'-O-hexoside-3,5-dimethoxyphenyl)-2-syrngaresinoxyl-propane-1,3-diol, 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid, linustatin and 1-deoxynojirimycin galactoside), were detected using high-resolution mass spectroscopy. The results revealed a significant concentration of phytoconstituents, making it an excellent contender for the pharmaceutical and food industries.
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In the therapy of cisplatin (CP), nephrotoxicity is a main limiting issue that associated with oxidative stress and apoptosis. According to many studies, the antioxidant and anti-inflammatory properties of Ajwa dates are very strong, due to the unique phytochemical profile. Here, we investigated the possible mitigative effects of Ajwa dates fruits extract (ADFE) vs CP-induced nephrotoxicity in rats, in addition to phytochemical profiling of its components via LC-MS/MS. Six groups were formed from forty-two male rats. G1: control, G2: ADFE 0.25 g/kg, G3: ADFE 0.5 g/kg (for 21 days), G4: CP -intoxicated group (single i.p. dose of 7.0 mg/kg b.w) on day 16th, G5: ADFE 0.25 + CP, G6: ADFE 0.5 + CP. LC-MS/MS analysis revealed the tentative identification of 17 compounds of different chemical nature, including organic/phenolic acids, and flavonoids and their sulphated/glycosides derivatives. ADFE has considerable antioxidant potential (DPPH with IC50 326.65 µg/ml and FRAP= 20.91 mM FeSO4/g extract) and total phenolic content (TPC = 35.44 mg/GAE/g extract). It (especially at dose 0.5 g/kg b.w) significantly modulated the toxicity of CP via enhancing food intake and hematobiochemical indices (renal functions, anemia, and leucopenia), increasing the renal antioxidant status (GSH, SOD, and CAT), decreasing the production of oxidative stress and inflammatory markers (MDA, NO, H2O2, MPO, MCP-1, TNF-α and IL-6), augmenting mRNA expression of Nrf2, and modulating NOX4 mRNA expression. The existence of bioactive compounds in ADFE may be responsible for their prophylactic properties, demonstrating natural usefulness in the treatment of oxidative stress, hypochromic anemia, immunodeficiency, and inflammatory complications, all of which are chemotherapy side effects.
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Phoeniceae , Animales , Masculino , Ratas , Antioxidantes/uso terapéutico , Cromatografía Liquida , Cisplatino/toxicidad , Peróxido de Hidrógeno/farmacología , Mediadores de Inflamación/farmacología , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Fenoles/farmacología , Phoeniceae/química , Extractos Vegetales/uso terapéutico , ARN Mensajero , Espectrometría de Masas en TándemRESUMEN
Ajwa dates (Phoenix dactylifera), cultivated particularly in Al-Madina Al-Monawarh in Saudi Arabia, and considered as a rich source of natural antioxidants such as anthocyanins, carotenoids and phenolics. It is believed that Ajwa dates have a wide range of protective effects. For this reason, this work aimed to investigate the ameliorative effect of Ajwa dates aqueous extract against ochratoxin A (OTA)-induced testicular lesions in rats. Rats were divided into four groups and treated for 28 days. Group I served as normal control, group II (OTA exposed) treated orally with 289 µg/kg/day. Group III (Ajwa dates aqueous extract) treated orally with 1 g/kg/day. The last group served as the protective group (pretreated with Ajwa dates extract, then OTA). Histological studies revealed that OTA induced lesions in the testicular structure included proliferation of sertoli cells, impairment of some spermatogenesis stages and accumulation of premeiotic germinal cells. However, pretreatment with Ajwa dates extract prevented all the testicular damage and improved spermatogenesis, as well as remarkably enhanced the testicular structure. In conclusion, Ajwa dates aqueous extract has a powerful protective effect and ameliorative influence against OTA- induced testicular damage and may be used to treat sexual impairment and male infertility.
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The aim of this study was to examine the variation in metabolite constituents of five commercial varieties of date fruits; Ajwa, Safawi and Ambar which originated from Madinah, the Iranian Bam and Tunisian Deglet Noor. The differences of metabolome were investigated using proton nuclear magnetic resonance (1H NMR) spectroscopy combined with multivariate data analysis (MVDA). Principal Component Analysis (PCA) revealed clear separation between the date varieties. The Tunisian Deglet Noor demonstrated distinct cluster from the rest of the palm date samples based on the metabolite composition as shown by the pattern observed in Hierarchical Clustering Analysis (HCA) and PCA. Deglet Noor exhibited a significant higher level of sucrose (δ 5.40) and fructose (δ 4.16) in comparison with the other four varieties which can be associated with the distinctive sweet taste of this variety. Dates originated from Madinah and Tunisia exhibited a contrast manner in the amount of xylose and moisture content. These two aspects may contribute towards the soft texture of Tunisian dates. All Madinah dates were found to contain phenolic compounds which were well established as great antioxidant and anti-inflammatory agent. Ajwa dates exerted greater effect in inhibiting the generation of nitric oxide (NO) from the stimulated RAW264.7 cells at 95.37% inhibition. Succinic acid was suggested to have the most significant correlation with the trend of NO inhibitory shown by the selected date palm varieties.
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ETHNOPHARMACOLOGICAL RELEVANCE: Phoenix dactylifera L. (Ajwa date) has high nutritive value and are consumed in Arabian Peninsula as an essential diet. Phoenix dactylifera L. have been mentioned in folk remedies of traditional Egyptian medicine and alternative medicine, for numerous health benefits including cancer treatment. The aim of the study is to evaluate the anticancer effects of the extract of Ajwa Date on human Prostate cancer cell line (PC3). MATERIALS AND METHODS: Antiproliferative effect was measured using MTT assay. The long-term effect of EAFAD was determined using colony assay. Different stains like Giemsa and fluorescent stains (DAPI and acridine orange / Ethidium bromide) measured morphological changes. Loss of mitochondrial membrane potential and increased oxidative stress were measured using JC-1 and DCFH-DA dyes. DNA degradation was analyzed by comet assay. Cell cycle distribution was measured by flow cytometer. The apoptotic cell was quantified by annexin V-FITC and Propidium iodide dual staining using flow cytometer. RESULTS: PC3 cell line was treated with ethyl acetate fractions of Ajwa dates (EAFAD) to study their morphological and cellular changes and induction of apoptosis. MTT assay showed the strong inhibitory effect of EAFAD on PC3 cells. Loss of mitochondrial membrane potential and increased oxidative stress were observed in EAFAD treated cells, which suggested mitochondrial involvement in apoptosis. Comet assay proved DNA fragmentation induced by EAFAD. Flow Cytometer results demonstrated that Annexin V-FITC and propidium iodide staining showed that EAFAD induced apoptosis and arrest the cell cycle in S phase. CONCLUSION: Our results suggested EAFAD has potential therapeutics properties for prostate cancer.
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Antineoplásicos Fitogénicos/farmacología , Phoeniceae , Extractos Vegetales/farmacología , Acetatos/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Fragmentación del ADN , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Solventes/químicaRESUMEN
This study was aimed at examining the variations in the metabolite constituents of the different Ajwa grades and farm origins. It is also targeted at establishing the correlations between the metabolite contents and the grades and further to the nitric oxide (NO) inhibitory activity. Identification of the metabolites was generated using ¹H-NMR spectroscopy metabolomics analyses utilizing multivariate methods. The NO inhibitory activity was determined using a Griess assay. Multivariate data analysis, for both supervised and unsupervised approaches, showed clusters among different grades of Ajwa dates obtained from different farms. The compounds that contribute towards the observed separation between Ajwa samples were suggested to be phenolic compounds, ascorbic acid and phenylalanine. Ajwa dates were shown to have different metabolite compositions and exhibited a wide range of NO inhibitory activity. It is also revealed that Ajwa Grade 1 from the al-Aliah farm exhibited more than 90% NO inhibitory activity compared to the other grades and origins. Phenolic compounds were among the compounds that played a role towards the greater capacity of NO inhibitory activity shown by Ajwa Grade 1 from the al-Aliah farm.
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Antiinflamatorios/farmacología , Óxido Nítrico/metabolismo , Phoeniceae/química , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/química , Ácido Ascórbico/análisis , Frutas/química , Metabolómica , Ratones , Estrés Oxidativo/efectos de los fármacos , Fenoles/análisis , Fenilalanina/análisis , Phoeniceae/clasificación , Extractos Vegetales/química , Espectroscopía de Protones por Resonancia Magnética , Células RAW 264.7RESUMEN
BACKGROUND/PURPOSE: Ajwa, a special variety of Saudi Arabian dates (Phoenix dactylifera L.) is a rich source of nutrients, fibers and bioactive molecules. While previous studies have shown the therapeutic value of dates phytoconstituents in liver and kidney diseases etc., its cardioprotective potential remains elusive. We therefore, investigated the cardioprotective effect of lyophilized Ajwa extract (AJLE) ex vivo as well as in vivo. METHODS: Ex vivo cardioprotective effect of AJLE was evaluated on DCFH-toxicated cardiomyoblast cells (H9C2). In vivo hemodynamics, cardiac function, serum cardiac enzymes, myocardial antioxidant, inflammatory and apoptotic biomarkers as well as histopathological parameters were studied in IPS-injured Wistar rat heart tissues. RESULTS: AJLE (250 µg/ml) attenuated the cytotoxicity and enhanced the H9C2 proliferation by up to 40%. Oral administration of AJLE (250 and 500 mg/kg.bw) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH and NO) and myocyte injury marker enzymes, and inhibited lipid peroxidation (MDA, MPO). Moreover, AJLE downregulated the expressions of proinflammatory cytokines (IL-6, IL-10 and TNFα) and apoptotic markers (caspase-3 and Bax), and upregulated the anti-apototic protein Bcl2. Histological data showed that AJLE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the cardiomyocytes architecture. CONCLUSION: Taken together, our data revealed that AJLE had strong antioxidant, hypolipidimic, cardioprotective, anti-inflammatory and anti-apoptotic potential against myocardial damage. This further endorses the use of Ajwa in Arabian traditional medicine against cardiovascular diseases.