Protective Effects of Propolis and Chitosan Nanoparticles against Ibuprofen-Induced Hepatotoxicity in Albino Rats.

Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver injury. Hepatitis is linked to systemic oxidative stress which results in cellular necrosis and fibrosis, as well as tissue lipoprotein peroxidation and glutathione depletion. Given the lack of safe and effective anti-hepatitis drugs in medicine today, natural substances appear to be a promising and safe alternative. Propolis and chitosan are considered natural substances that have a protective effect on the hepatocytes. The purpose of this study was to validate the protective effect of propolis/chitosan nanoparticle extracts on ibuprofen-induced hepatotoxicity. Thirty (30) albino rats were used for the experiment. Animals were exposed to ibuprofen (400 mg/kg body weight/day) for 4 weeks (7 days/week) followed by treatment with propolis (200 mg/kg body weight/day) and chitosan extract (200 mg/kg body weight/day) separately and also in combination for consecutive 4 weeks. This study revealed a significant increase in serum transaminases, alkaline phosphatase, albumin, and total bilirubin in serum, as well as an increase in lipid peroxidation (MDA) and nitric oxide (NO). Furthermore, GSH, GST, and SOD decreased significantly in the group that was exposed to ibuprofen. Furthermore, there was a significant increase in pro-inflammatory parameters such as IL-1ß and NF-ĸB, as well as low levels of anti-inflammatory parameters such as IL-6 and BCl-2. These alterations were improved by propolis and chitosan extracts, which was further confirmed in experimental animals. This study demonstrated that propolis and chitosan nanoparticle extracts have the potential to protect against hepatotoxicity induced by ibuprofen, due to their ability to regulate anti-inflammatory and anti-oxidative defense activities.

In silico investigation and potential therapeutic approaches of isoquinoline alkaloids for neurodegenerative diseases: computer-aided drug design perspective.

Microtubule affinity regulating kinase (MARK4) has been proposed as a potential therapeutic target for diabetes, cancer, and neurological diseases. We used a variety of computational studies techniques to examine the binding affinity and MARK4 inhibitory potential of several isoquinoline alkaloids. MARK4 has been associated with tau protein phosphorylation and, consequently, Alzheimer's disease. The three molecules with the highest binding affinities inside the 5ES1 receptor, according to molecular docking experiments, are isoliensinine, liensinine, and methylcorypalline. Isoliensinine had the highest drug score and drug likeness, coming in at 1.17, while Liensinine and Methylcorypalline came in at 1.15 and 1.07, respectively. The thesis claims that three compounds have a better chance than the others of being identified as therapeutic leads. The bulk of the compounds under investigation didn't break any of Lipinski's five rules, especially methylcorypalline, which did and is probably orally active. The majority of the compounds under investigation, particularly Isoliensinine, Liensinine, and Methylcorypalline, show the potential to exhibit drug-like behaviour, which is strongly confirmed by ADMET characteristics estimates. The chemicals Isoliensinine, Liensinine, and Methylcorypalline, especially Methylcorypalline, form the most stable combination with the 5ES1, according to a 100 ns molecular dynamics simulation of these compounds docked inside 5ES1 complexes. Methylcorypalline has a higher binding affinity inside 5ES1, according to additional MM/GBSA experiments using MD trajectories. Overall, research supports the use of the drug development tool methylcolipalin for its ability to inhibit MARK4, which may have implications for the treatment of neurodegenerative diseases.Communicated by Ramaswamy H. Sarma.

Identification of potent COVID-19 main protease inhibitors by loading of favipiravir on Mg12O12 and Zn12O12 nanoclusters: an in silico strategy for COVID-19 treatment.

Pandemic new severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has increased throughout the world. There is no effective treatment against this virus until now. Since its appearance in Wuhan, China in December 2019, SARS-CoV-2 becomes the largest challenge the world is opposite today, including the discovery of an antiviral drug for this virus. Several viral proteins have been prioritized as SARS-CoV-2 antiviral drug targets, among them the papain-like protease (PLpro) and the main protease (Mpro). Inhibition of these proteases would target viral replication, viral maturation and suppression of host innate immune responses. Potential candidates have been identified to show inhibitory effects against Mpro, both in biochemical assays and viral replication in cells. There are different molecules such as lopinavir and favipiravir considerably inhibit the activity of Mpro in vitro. Different studies have shown that structurally improved favipiravir and other similar compounds can inhibit SARS-CoV-2 main protease. In this work, we study the interactions between favipiravir with Mg12O12 and Zn12O12 nanoclusters by density functional theory (DFT) and quantum mechanics atoms in molecules (QMAIM) methods to summarize the ability to load favipiravir onto Mg12O12 and Zn12O12 nanoclusters. Favipiravir-Mg12O12 and favipiravir-Zn12O12 lowest structures complexes were chosen to dock inside the SARS-CoV-2 main protease by molecular docking study. The molecular docking analysis revealed that the binding affinity of Mg12O12 and Zn12O12 nanoclusters inside the Mpro receptor is larger than that of favipiravir. Also, the loading of favipiravir on the surface of Mg12O12 and Zn12O12 nanoclusters increased the binding affinity against the Mpro receptor. Subsequently, 100 ns molecular dynamics simulation of the favipiravir-Mg12O12, and favipiravir-Zn12O12 docked inside the Mpro complexes established that favipiravir-Mg12O12, forms the most stable complex with the Mpro. Further molecular mechanics Poisson Boltzmann surface area (MMPBSA) analyses using the MD trajectories also demonstrated the higher binding affinity of favipiravir-Mg12O12 inside the Mpro. In summary, this study demonstrates a new way to characterize leads for novel anti-viral drugs against SARS-CoV-2, by improving the drug ability of favipiravir via loading it on Mg12O12 and Zn12O12 nanoclusters.Communicated by Ramaswamy H. Sarma.

Computational and Molecular Docking Studies of New Benzene Sulfonamide Drugs with Anticancer and Antioxidant Effects.

BACKGROUND: The studies on the potential usage of benzene sulfonamide derivatives as anticancer agents are limited. benzene sulfonamide derivatives are currently used as anticancer agents against different breast cancer cell lines, such as MCF-7, lung cancer cells (A549), prostate cancer cells (Du-145), and cervical cells (HeLa). OBJECTIVE: A series of new sulfonamide drugs are synthesized by reacting aldehydes thio-semi-carbazones derivatives with benzene sulphonyl chloride to form benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide derivatives. Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. METHODS: Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. To study the anti-breast cancer activity of the newly synthesized compounds, a molecular docking study is used to analyze the binding energy for the nonbonding interactions between the ligands (studied compounds) and receptor (4PYP (pdb code: 4FA2)) against human breast cancer (MCF-7) cells. The bioavailability of all studied compounds is confirmed by pharmacological investigations using Mol inspiration and absorption, distribution, metabolism, excretion, and toxicity online servers. RESULTS: The two derivatives, 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4c) and 2-(4-dimethylamino) benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4e) show the most potent anticancer effects against MCF-7 breast carcinoma cell lines. Meanwhile, these two derivatives show the lowest antioxidant activities. CONCLUSION: The different spectral techniques were used to confirm the structure of the novel synthesized compounds. Further, 2-(4-(dimethyl amino) benzylidene)-N- (phenylsulfonyl)hydrazine-1-carbothioamide (4e) and 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1 carbothioamide (4c) were the most potent anticancer derivatives against MCF-7 breast carcinoma cell lines. Furthermore, they exhibited the most potent antioxidant activities. Meanwhile, the 2-benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4a) and 2-(4-chloro benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4d) had the lowest antioxidant potentials. The estimated binding energies, inhibition constant, intermolecular energies, and reference RMSD produced from docking for all studied compounds were reported. These values showed that all studied compounds formed stable complexes with the receptor with high binding affinity. It was further noted from the ADMET analysis that compounds 4c, 4d, and 4e have good absorption, low toxicity in the human liver, and medium BBB penetration. Hence, these studied compounds (4c-4e) may be suggested as potential compounds against human breast cancer MCF-7 cells.

Evaluation of the phycoremediation potential of microalgae for captan removal: Comprehensive analysis on toxicity, detoxification and antioxidants modulation.

Captan is one of the most widely used organochlorine fungicides, its frequent application contaminates both terrestrial and aquatic ecosystems and negatively affects their key ecological processes. This study demonstrated the toxicity and efficient removal of captan by two different taxonomic species; the green microalga Scenedesmus obliquus and cyanobacterium Nostoc muscorum. After a week of exposure to mild (15 mg/L) and severe (30 mg/L) captan doses, the intracellular captan uptake, degradation and metabolic regulation of captan detoxification were studied. Compared to N. muscorum, S. obliquus accumulated more captan, but efficiently degraded it into two safe eco-friendly by-products; phthalic acid and 1,2,3,6-tetrahydro phthalimide. S. obliquus showed less decrease in cell growth, photosynthesis activity and related parameters including Chla content and activity of PEPC and RuBisCo enzymes. Captan at the severe dose induced oxidative damage particularly in N. muscorum, as expressed by the high levels of H2O2, MDA, NADPH oxidase and protein peroxidation. Both species invested glutathione-s-transferase enzyme in captan detoxification however, induction of antioxidant defence system e.g. ascorbate and glutathione cycle was more pronounced in S. obliquus which could explain its tolerance ability. This study provided a better understanding of the environmental risks of captan and introduced S. obliquus as a promising captan phycoremediator.

Experimentally and theoretically approaches for disperse red 60 dye adsorption on novel quaternary nanocomposites.

A comprehensive study that combined both experimental and computational experiments was performed to evaluate the usage of organo-metal oxide nanocomposite for the elimination of disperse red 60 dye (DR) from aqueous solutions. Chitosan was modified by Schiff base to form nanoneedles chitosan-4-chloroacetophenone derivative. The derivatives were then impregnated with CeO2-CuO-Fe2O3 or CeO2-CuO-Al2O3 metal oxides to prepare a novel quarternary organo-metal oxide nanocomposite. The novel nanocomposite, chitosan-4-chloroacetophenone/CeO2-CuO-Fe2O3 (CF) and chitosan-4-chloroacetophenone/CeO2-CuO-Al2O3 (CA) are cheap and effective nano adsorbents that can be used for the uptake of DR from aqueous solution. The CF and CA nano-composites were characterized using different techniques. Moreover, the effect of adsorption parameters (initial DR concentration, time of contact, pH, temperature, and adsorbent mass) as well as CA and CF reusability tests were performed. Langmuir adsorption isotherm and pseudo-second-order kinetics models were best fitted with the adsorption process. The maximum amount of DR adsorbed was 100 mg/g on CF and CA at pH 2 and 4, respectively with a physical spontaneous, and exothermic adsorption process. Monte Carlo (MC) simulation studies indicated the adsorption of DR molecule on the CF and CA surfaces following a parallel mode in most of all studied configurations, confirming the strong interactions between the DR and surfaces atoms of CF and CA. The molecular structure analysis of DR dye adsorbed on the surface of CF and CA indicated that the adsorption process related to Van der Waals dispersion force. Consequently, this helps to trap DR dye molecules on the surface of CF and CA (i.e., physical adsorption), which supports our experimental results.

Combination and tricombination therapy to destabilize the structural integrity of COVID-19 by some bioactive compounds with antiviral drugs: insights from molecular docking study.

Recently, the SARS-CoV-2 (COVID-19) pandemic virus has been spreading throughout the world. Until now, no certified drugs have been discovered to efficiently inhibit the virus. The scientists are struggling to find new safe bioactive inhibitors of this deadly virus. In this study, we aim to find antagonists that may inhibit the activity of the three major viral targets: SARS-CoV-2 3-chymotrypsin-like protease (6LU7), SARS-CoV-2 spike protein (6VYB), and a host target human angiotensin-converting enzyme 2 (ACE2) receptor (1R42), which is the entry point for the viral encounter, were studied with the prospects of identifying significant drug candidate(s) against COVID-19 infection. Then, the protein stability produced score of less than 0.6 for all residues of all studied receptors. This confirmed that these receptors are extremely stable proteins, so it is very difficult to unstable the stability of these proteins through utilizing individual drugs. Hence, we studied the combination and tricombination therapy between bioactive compounds which have the best binding affinity and some antiviral drugs like chloroquine, hydroxychloroquine, azithromycin, simeprevir, baloxavir, lopinavir, and favipiravir to show the effect of combination and tricombination therapy to disrupt the stability of the three major viral targets that are mentioned previously. Also, ADMET study suggested that most of all studied bioactive compounds are safe and nontoxic compounds. All results confirmed that caulerpin can be utilized as a combination and tricombination therapy along with the studied antiviral drugs for disrupting the stability of the three major viral receptors (6LU7, 6VYB, and 1R42). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11224-020-01723-5.

Bis-indole alkaloid caulerpin from a new source Sargassum platycarpum: isolation, characterization, in vitro anticancer activity, binding with nucleobases by DFT calculations and MD simulation.

Caulerpin, a bis-indole alkaloid is isolated from a new source Sargassum platycarpum, brown alga (family Sargassaceae) for the first time. The structure of caulerpin was characterized by IR, H1NMR, C13 NMR, HSQC, HMBC, EI-MS spectroscopy. Antifungal results suggest that caulerpin has been inhibited Cryptococcus neoformas (12 mm) and Candida albicans (7 mm) than other microbes. In vitro anticancer activity of caulerpin has been explored by cell viability assay against new human cancer cell line (liver-HepG2). The results show that caulerpin has low IC50 value (24.6 ± 2.1 µg/mL) against HepG-2. Based on the least toxic activity of caulerpin, these results encourage for future in vivo anticancer study. The binding of caulerpin molecule with the two nucleobases (T/U) bases has been studied by DFT methods. According to the AIM analysis, there are two types of interactions between caulerpin and T/U bases partially covalent partially electrostatic and electrostatic in gas and water phases. Based on NBO analysis, the charges were transferred from the lone-pair (n) in orbitals of O atoms of caulerpin to the σ* orbitals of T/U bases atoms. ΔEbin in the state of caulerpin-T bases complexes are lower than those in the caulerpin-U bases complexes in both gas and water phase. MD simulation supported that caulerpin-T/U bases complexes are stable in presence of explicit water phase. Thus, the findings of our study will be useful for giving an insight into the caulerpin/bases complexes that could be helpful in future experimental studies to develop the performance of caulerpin molecules as natural candidate drug. Communicated by Ramaswamy H. Sarma.

Cytotoxic activity, molecular docking, pharmacokinetic properties and quantum mechanics calculations of the brown macroalga Cystoseira trinodis compounds.

In this study, nine compounds were isolated, eight of them were isolated for the first time from Cystoseira trinodis. The biological activity of the extract, fractions and pure compounds was evaluated. The antimicrobial activity was investigated against 3 fungi species, 3 gram + ve and 3 gram -ve bacteria. The crude extract and fractions showed moderate inhibition against some of the tested microorganisms, especially the butanol fraction exhibited the maximum inhibition zone against Salmonella typhimurium (16 ± 0.60 mm). Cytotoxicity was evaluated against HepG-2 and MCF-7 cell lines. Hexane fraction exhibited the highest cytotoxic effect against HepG-2 and MCF-7 cell lines with an IC50 value of 14.3 ± 0.8 and 19.2 ± 0.7 µg/ml, respectively with compared to other fractions. The isolates were identified as octacosanoic acid (1), glyceryl trilinoleate (2), oleic acid (3), and the epimeric mixture of saringosterols (4, 5), ß-sitosterol (6), glycoglycerolipid (7) and a mixture of kjellmanianone and loliolide (8, 9) by spectroscopic analysis. Among the all tested compounds kjellmanianone and loliolide mixture exhibited significant cytotoxic activity with an IC50 value of 7.27 µg/ml against HepG-2 cells. The major and minor constituents of the extract and fractions were identified using GC-MS analysis. Molecular docking analysis confirmed that most of the studied compounds especially compounds 8 and 9 strongly interact with TPK and VEGFR-2 with highest binding energies supported that the high cytotoxicity of these compounds against human hepatocellular cancer in the experimental part. The energetic, geometric and topological properties of compounds 8 and 9 binding with cytosine base were computed by DFT methods. Molecular properties descriptors, bioactivity score and ADMET analysis confirmed that most of the studied compounds especially compounds 8 and 9 exhibit significant biological activities and have a better chance to be developed as drug leads. Communicated by Ramaswamy H. Sarma.

Dissipation of pyridaphenthion by cyanobacteria: Insights into cellular degradation, detoxification and metabolic regulation.

Excessive use of organophosphorus pesticides such as pyridaphenthion (PY) to constrain insects induced crop loss, results in soil and water sources contamination. Cyanobacteria are sensitive biological indicators and promising tools for bioremediation of soil and water pollutants. To understand PY toxicity, detoxification and degradation in cyanobacteria, we performed a comparative study in the two diazotrophic cyanobacteria; Anabaena laxa and Nostoc muscorum. They were exposed to mild (5 mg/L) and high (10 mg/L) concentrations of PY for 7 days. Compared to A. laxa, N. muscorum efficiently showed high PY accumulation and degradation to a safe environmentally product; 6-hydroxy-2-phenylpyridazin-3(2 H)-one. PY inhibited cell growth and reduced Chl a content and photosynthesis related enzymes (PEPC and RuBisCo) activities in both species, but to less extend in N. muscorum. It also induced oxidative damage, particularly in A. laxa, as indicated by high H2O2, lipid peroxidation and protein oxidation levels and increased NADPH oxidase enzyme activity. N. muscorum invested more in antioxidants induction, i.e., induced ascorbate and glutathione cycle, however, these antioxidants increments in A. laxa were less pronounced. Overall, this study provides more in-deep insights into the PY toxicity and the role of N. muscorum as a promising PY remediator.

The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation.

This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1-10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski's rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment.

Destabilizing the structural integrity of COVID-19 by caulerpin and its derivatives along with some antiviral drugs: An in silico approaches for a combination therapy.

Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of these drugs by using caulerpin and its derivatives as an adjunct drug against SARS-CoV-2 receptor proteins: the SARS-CoV-2 main protease and the SARS-CoV-2 spike protein. Caulerpin exhibited antiviral activities against chikungunya virus and herpes simplex virus type 1. Caulerpin and some of its derivatives showed inhibitory activity against Alzheimer's disease. The web server ANCHOR revealed higher protein stability for the two receptors with disordered score (< 0.6). Molecular docking analysis showed that the binding energies of most of the caulerpin derivatives were higher than all the suggested drugs for the two receptors. Also, we deduced that inserting NH2, halogen, and vinyl groups can increase the binding affinity of caulerpin toward 6VYB and 6LU7, while inserting an alkyl group decreases the binding affinity of caulerpin toward 6VYB and 6LU7. So, we can modify the inhibitory effect of caulerpin against 6VYB and 6LU7 by inserting NH2, halogen, and vinyl groups. Based on the protein disordered results, the SARS-CoV-2 main protease and SARS-CoV-2 spike protein domain are highly stable proteins, so it is quite difficult to unstabilize their integrity by using individual drugs. Also, molecular dynamics (MD) simulation indicates that binding of the combination therapy of simeprevir and the candidate studied compounds to the receptors was stable and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. So, this study suggested that caulerpin and its derivatives could be used as a combination therapy along with lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir for disrupting the stability of SARS-CoV2 receptor proteins to increase the antiviral activity of these drugs.

Adsorption of Cd2+ and Cr3+ ions from aqueous solutions by using residue of Padina gymnospora waste as promising low-cost adsorbent.

Recently, a great attention has been given for applying a low-cost and effective adsorbents instead of expensive and dangerous chemical materials as a promising approach to treat wastewater. In this work, residue powder of brown macroalga Padina gymnospora (RPG), after extracting most of its active components by 70% methanol, was used as an adsorbent material for wastewater treatment. This work also reduces the costs of residue disposal. The adsorption ability of RPG is studied for removing Cd2+ and Cr3+from wastewater. We investigated metal adsorption isotherms and kinetics, the effect of initial metal concentration, contact time, adsorbent dosage, temperature, pH and the RPG reusability on metal ions removal. The results showed that the removal % generally increases with decreasing concentration of metal ions. RPG has higher metal removal percentages reaching 96.2% and 78.8% for Cd2+ and Cr3+, respectively, with a maxiumum adsorption capacity of 96.46 and 31.52 mg/g for Cd 2+ and Cr3+,respectively at pH 6.2, 50 mg, 25 °C and initial metal concentration of 100 mg/L. The metal ions removal % increased by increasing the dosage of adsorbent and it decreased after a certain limit. The metal removal % slightly changes with increasing temperature for Cd2+ and decreased at high-temperature for Cr3+. The adsorption increased with increasing pH value from 3 to 5, and decreases at pH value of 6.2 then it increased again at pH 8. The removal % and adsorption capacity at pH 8 reaches 99.58%, 99.65%, 99.85 mg/g and 39.86 mg/g for Cd2+ and Cr3+, respectively. The results also showed that RPG can be reused several times for metal ions removal. In addition, Tempkin isotherms and pseudo-second-order kinetic fit the adsorption of Cd2+ and Cr3+ well.

Utilization of actinobacteria to enhance the production and quality of date palm (Phoenix dactylifera L.) fruits in a semi-arid environment.

Actinobacteria have received much attention due to their capacity for plant growth promotion, a promising approach in sustainable development of agriculture. Date palm (Phoenix dactylifera L.) is an important crop, particularly in semi-arid regions of the world, due to the high nutritional and health-promoting values of its fruits. The present study was conducted to investigate the utilization of actinobacteria as an approach to support soil fertility and enhance production and functional food value of date palm fruits in a semi-arid environment. To achieve this purpose, actinobacterial strains were isolated from palm rhizosphere, characterized and screened for bioactivity. Then the potent isolates, based on plant growth promoting assays, were inoculated into the soil rhizosphere of five-target palms (Ajwa, Sokary, Khodry, Rashodia and Saffawy) before flowering and during fruiting stages in two successive seasons. Interestingly, the actinobacterial inoculants increased soil fertility and improved fruit yield of the tested palms. The treated date fruits accumulated higher levels of valuable phytochemicals such as sugars, organic acids, essential amino acids, unsaturated fatty acids, phenolic acids, flavonoids, vitamins and minerals, as compared with the untreated ones. Moreover, actinobacterial treatment induced the biological activities (antioxidant, antibacterial, antifungal and anticancer) of the produce dates. Conclusively, results presented herein suggest the promising application of actinobacteria for supporting the production and functional food value of date palms in semi-arid regions.