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Mohammed Mubarak Aljeldah,1 Mohamed Taha Yassin,2 Ashraf Abdel-Fattah Mostafa,2 Mourad AM Aboul-Soud3 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al-Batin, Saudi Arabia; 2Botany and Microbiology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 3Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Mohammed Mubarak Aljeldah, College of Applied Medical Sciences, University of Hafr Al Batin, Email mmaljeldah@uhb.edu.sa Mourad AM Aboul-Soud, Chair of Medical and Molecular Genetics Research, College of Applied Medical Sciences, King Saud University, Email Maboulsoud@ksu.edu.saIntroduction: A considerable number of morbidities and fatalities occur worldwide as a result of the multidrug resistant microorganisms that cause a high prevalence of nosocomial bacterial infections. Hence, the current investigation was conducted to evaluate the antibacterial potency of green fabricated silver nanoparticles (AgNPs) against four different nosocomial pathogens.Methods: The flower extract of Hibiscus sabdariffa mediated green fabrication of AgNPs and their physicochemical features were scrutinized using different techniques. Antimicrobial activity of the biogenic AgNPs and their synergistic patterns with fosfomycin antibiotic were evaluated using disk diffusion assay.Results and Discussion: UV spectral analysis affirmed the successful formation of AgNPs through the detection of broad absorption band at 395 and 524 nm, indicating the surface plasmon resonance of the biofabricated AgNPs. In this setting, the biofabricated AgNPs demonstrated average particle size of 58.682 nm according to transmission electron microscope (TEM) micrographs. The detected hydrodynamic diameter was higher than that noticed by TEM analysis, recording 72.30 nm in diameter and this could be attributed to the action of capping agents, which was confirmed by Fourier Transform Infrared (FT-IR) analysis. Disk diffusion assay indicated the antibacterial potency of biogenic AgNPs (50 μg/disk) against Enterobacter cloacae, Methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli strains with relative inhibition zone diameters of 12.82 ± 0.36 mm, 14.54 ± 0.15 mm, 18.35 ± 0.24 mm and 21.69 ± 0.12 mm, respectively. In addition, E. coli was found to be the most susceptible strain to the biogenic AgNPs. However, the highest synergistic pattern of AgNPs-fosfomycin combination was detected against K. pneumonia strain recording relative synergistic percentage of 64.22%. In conclusion, the detected synergistic efficiency of AgNPs and the antibiotic fosfomycin highlight the potential for utilizing this combination in the biofabrication of effective antibacterial agents against nosocomial pathogens.Keywords: green synthesis, Hibiscus sabdariffa, silver nanoparticles, resistance, synergism, fosfomycin

Despite progress in medical and surgical treatments of wounds, bioactive compounds still offer an effective and safe approach to accelerate wound healing (WH). In this review, recent results of studies on WH by essential oils (EOs) and their terpenoids are reported. Mechanisms of action of these substances and their possible use in drug delivery systems (DDSs) for WH are discussed. EOs of 38 species from 16 families have been evaluated for their potential to treat wounds. Lamiaceae was the most representative family with 10 species, followed by Myrtaceae and Asteraceae. EOs improve WH by acting as anti-inflammatory, antioxidant, and antimicrobial agents. Some other EOs were involved by increasing expression of transforming growth factor (TGF), inhibition of several factors, including plasminogen activator inhibitor-1 (PAI-1), substitution of type III collagen by type I collagen, and up-regulation of insulin-like growth factor-1 (IGF-1), fibroblast growth factor 2 (FGF-2), and vascular endothelial growth factor (VEGF). These mechanisms improved repair of cells and increased proliferation. Alternatively, DDSs based on nanomaterials (NMs) used to carry EOs for WH are mainly based on nanoparticles (NPs), microparticles (MPs) and scaffolds. There is much evidence that EOs can promote WH. Advancement of nanotechnology in recent years has contributed to improving use of EO with DDSs in WH management. However, some limitations need to be addressed to achieve the translation of this technology into clinical applications for wound treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd and ISBI. All rights reserved.)

Caralluma europaea Guss. ( C. europaea ) is a medicinal plant used for cancer treatment. However, these treatments may be associated with complications that need to be investigated. This work aims to evaluate not only the chemical composition but also the hepatoprotective and anticancer properties of C. europaea extracts. The chemical constitution of the hydroethanolic extract was explored using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). The hydroethanolic extract, flavonoids, and polyphenols-rich extract at 100, 15, and 50 mg/kg, respectively, were administered to acetaminophen-treated rats for seven days. We used Western blotting and Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) to determine the protein and the mRNA levels of cancer stemness markers in pancreatic cancer cell lines MIA PaCa-2 and BxPC-3 exposed to increasing doses of C. europaea extracts. In silico analysis was used to evaluate the effects of phenolic compounds revealed in C. europaea on caspase-3 and HSP90, and on liver damage on CYP2E1. The primary phenolics detected by GC-MS and HPLC were ferulic acid and benzofurazan. The positive control group showed an increase in AST, ALT, ALP, triglycerides, and VLDL levels. C. europaea extracts demonstrated hepatoprotective effects by ameliorating acetaminophen-induced alterations of biochemical and hispathological parameters. Immunoblotting and RT-qPCR profiling of cancer stemness markers indicated a reduction in the expression levels of Oct-4 and Nanog proteins, as well as a reduction in the mRNA levels of CD133 by 50-60% and Sox2 by 80-90% in pancreatic cancer cells. Molecular docking showed that naringenin presented the highest docking Gscore on CYP2E1 (-8.199) and HSP90 (-7.742). In conclusion, C. europaea extracts could be considered as a safe and promising therapeutic strategy to sensitize pancreatic cancer cells to chemotherapy.

Ethnopharmacological Relevance: In Moroccan traditional medicine, plants from the Apiaceae family are widely utilized in folk medicine to treat various diseases associated with the digestive system. Ammodaucus leucotrichus plays an important role as an antispasmodic that has been traditionally used, especially to treat digestive tract diseases in children., Aim of the Study: The aim of this research was to verify the traditional use by assessing the relaxant and spasmolytic activities of A. leucotrichus essential oil (ALEO) and then comparing them to the effects and potency of the major constituent of ALEO, which is perillaldehyde., Materials and Methods: The in vitro evaluation of ALEO's relaxant and spasmolytic effects was carried out on isolated rats and rabbit jejunum in an organ bath setup. Intestinal contractility was recorded using an isotonic transducer connected to an amplifier. GC/MS analysis was conducted to identify components within ALEO. Subsequently, these compounds underwent in silico absorption, toxicity, and molecular docking studies., Results: GC/MS analysis of this essential oil studied revealed seven compounds, which account for 98.67% of the oil, with the dominance of two compounds, namely, perillaldehyde (91.12%) and limonene (6.33%). ALEO and its main compound, perillaldehyde, reversibly relaxed the basal tone of rabbit jejunum, with the IC 50 values 158.68 ± 13.89 and 95.03 ± 0.93 μg/mL, respectively. Moreover, ALEO caused a dose-dependent spasmolytic effect on Carbachol (CCh) and KCl provoked jejunum contraction in rats. Furthermore, the decrease in contractions of pre-contracted jejunum by CCh was more pronounced for perillaldehyde compared to ALEO, with an IC 50 value of 68.59 ± 6.57 μg/mL, which was half compared to that of ALEO. The pre-treatment of the tissue with concentrations ranging from 30 to 100 μg/mL caused a rightward and downward shift in the concentration-response curves for CaCl 2 and CCh. These results suggest that the spasmolytic effect of ALEO is mediated possibly through a non-competitive antagonist of calcium channel or muscarinic receptors. Our results are confirmed by the fact that perillaldehyde exhibited the highest docking scores on muscarinic acetylcholine receptors (M 2 and M 3 ) and voltage-gated calcium channels, with D-limonene showing lower binding energies in comparison. These remarks confirm that the activity of ALEO is attributed to the presence of perillaldehyde. In addition, perillaldehyde exhibits a low degree of in silico acute toxicity and high percent of intestinal absorption., Conclusion: In summary, ALEO exhibits myorelaxant and antispasmodic effects by inhibiting muscarinic receptors and calcium channels, which can be attributed to the presence of perillaldehyde. This provides a scientific foundation for the traditional use of A. leucotrichus in treating gastrointestinal disorders and opens up possibilities for developing a more effective and less toxic drug-utilizing perillaldehyde., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Karim, Marghich, Amrani, Addous, Malek, Beyi, Harit, Aldisi, Aboul-Soud, Giesy and Aziz.)

Artemisia absinthium L., is a plant with established pharmacological properties, but the A. absinthium root extract (AARE) remains unexplored. The aim of this study was to examine the chemical composition of AARE and assess its biological activity, which included antidiabetic, antibacterial, anticancer, and antioxidant properties. GC-MS was used to analyze the chemical components. The antioxidant activity of the total phenolic and flavonoid content was evaluated. Antibacterial activity and cytotoxic effects were identified. Enzyme inhibition experiments were performed to determine its antidiabetic potential. Molecular docking was utilized to evaluate the potential antioxidant, antibacterial, and anticancer activities of the compounds from AARE using Maestro 11.5 from the Schrödinger suite. AARE exhibited moderate antioxidant activity in DPPH (IC 50 : 172.41 ± 3.15 μg/mL) and ABTS (IC 50 : 378.94 ± 2.18 μg/mL) assays. Cytotoxicity tests on MCF-7 and HepG2 cancer cells demonstrated significant anticancer effects, with IC 50 values of 150.12 ± 0.74 μg/mL and 137.11 ± 1.33 μg/mL, respectively. Apoptotic studies indicated an upregulation of pro-apoptotic genes ( caspase - 3 , 8 , 9 , Bax ) and a downregulation of anti-apoptotic markers ( Bcl-2 and Bcl-Xl ). AARE also inhibited α-amylase and α-glucosidase, suggesting potential antidiabetic effects, with IC 50 values of 224.12 ± 1.17 μg/mL and 243.35 ± 1.51 μg/mL. Antibacterial assays revealed strong activity against Gram-positive bacteria. Molecular docking and pharmacokinetic analysis identified promising inhibitory effects of key AARE compounds on NADPH oxidase, E. coli Gyrase B, and Topoisomerase IIα, with favorable drug-like properties. These findings suggest AARE's potential in treating cancer, diabetes, and bacterial infections, warranting further in vivo and clinical studies.

Background: Salvia blancoana subsp. mesatlantica (Maire) Figuerola (SBm) is a plant endemic to Morocco and is one of the less studied species of Salvia. Herbal therapy is becoming more and more popular, especially in underdeveloped nations where access to medicinal herbs is affordable. However, some plants demonstrated toxic effects in animals and humans., Objective: Our study aimed to evaluate the SBm-extract for both acute and sub-chronic toxicity., Methods: Aqueous extracts were obtained from the aerial parts of SBm collected from Immouzer Kander commune (Middle Atlas, Morocco). Total Phenolic Content (TPC) and Flavones and flavonols Content (FFC), Antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power) was determined, and chemical composition was determined by High-Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD). Toxicity tests were conducted on mice and rats., Results: In acute toxicity, Swiss albino mice (mass of 25-35 g) received SBm-extract orally and intraperitoneally at doses (0.5-11 g/kg, bm). The sub-chronic toxicity was tested in Wistar albino rats (mass of 200-240 g) for 90 days at doses of 0, 250, 500, or 1000 mg/kg, bm. Values of TPC and FFC were estimated to be 157.56 ± 0.32 mg GAE/g DW and 7.89 ± 0.05 mg QE/g DW, respectively. DPPH scavenging (IC 50 ) was estimated to be 26.9 ± 0.08 µg/mL while reducing power was 12.41 ± 0.03 µg/mL. No toxicity or deaths were observed in acute tests after oral exposure, while intraperitoneal administration resulted in dose-dependent acute toxicity, with an LD 50 value of 6.82 g/kg. In sub-chronic tests, most hematological and biochemical parameters remained unchanged, except for transient fluctuations in specific blood constituents and a transitory reduction in serum glucose levels observed at elevated dosages. Histopathological investigation revealed no organ abnormalities. The SBm-extract exhibited minimal toxicity, supporting its safe use., Conclusions: Despite the relevant results of this study, future studies need to confirm these findings and expand our understanding of the safety characteristics of Salvia . Further investigations are needed to explore the effects of other solvents on the extraction of bioactive compounds from the underground and aerial parts of this endemic species. Evaluation of other biological properties such as anti-microbial, anti-cancer, and anti-inflammatory activities are needed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study focused on analyzing the pharmacological activities of AgNPs synthesized from an aqueous plant extract of Anchusa arvensis . The effectiveness of AgNPs was evaluated for protein kinase inhibition, antioxidant, antibacterial, and antifungal activities. The AgNPs and plant were used to regulate the protein kinase activity using the liquid TSB and ISP4 medium protein kinase inhibition study demonstrated that nanoparticles exhibited a larger zone of inhibition (9.1 ± 0.8) compared to the plant extract (8.1 ± 0.6). The antioxidant activity was assessed using DPPH reagent, and the results indicated that AgNPs displayed potent free radical scavenging properties. In terms of antibacterial activity, AgNPs showed higher efficacy against Enterobacter aerogens (20.1 ± 0.9), Bordetella bronchiseptaca (19.1 ± 0.9), and Salmonella typhimurium (17.2 ± 0.8) at 4 mg/mL. The antifungal activity of AgNPs was prominent against Aspergillus fumagatus (14.1 ± 0.9), Mucor species (19.2 ± 0.8), and Fusarium solani (11.2 ± 0.8) at 20 mg/mL. These findings suggest that AgNPs possess multiple beneficial properties, including bactericidal/fungicidal effects, protein kinase inhibition, and potential free radical scavenging abilities. Therefore, AgNPs have potential applications in various fields, such as biomedicine and industry, due to their ability to counteract the harmful effects of free radicals., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Monkeypox virus (MPV) infection has developed into a re-emerging disease, and despite the potential of tecovirimat and cidofovir drugs, there is currently no conclusive treatment. The treatment's effectiveness and cost challenges motivate us to use In Silico approaches to seek natural compounds as candidate antiviral inhibitors. Using Maestro 11.5 in Schrodinger suite 2018, available natural molecules with validated chemical structures collected from Eximed Laboratory were subjected to molecular docking and ADMET analysis against the highly conserved A42R Profilin-like Protein of Monkeypox Virus Zaire-96-I-16 (PDB: 4QWO) with resolution of 1.52 Å solved 3D structure. Compared to the FDA-approved Tecovirimat, molecular docking revealed that Salsoline derivatives, Genistein, Semisynthetic derivative of kojic acid, and Naringenin had strengthened affinity (-8.9 to -10 kcal/mol) to 4QWO, and the molecular dynamic's simulation confirmed their high binding stability. In support of these results, the hydrogen bond analysis indicated that the Salsoline derivative had the most robust interaction with the binding pockets of 4QWO among the four molecules. Moreover, the comparative free energy analyses using MM-PBSA revealed an average binding free energy of the complexes of Salsoline derivative, Genistein, Semisynthetic derivative of kojic acid, Naringenin, of -106.418, -46.808, -50.770, and -63.319 kJ/mol, respectively which are lower than -33.855 kJ/mol of the Tecovirimat complex. Interestingly, these results and the ADMET predictions suggest that the four compounds are promising inhibitors of 4QWO, which agrees with previous results showing their antiviral activities against other viruses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chebaibi, Bourhia, Amrati, Slighoua, Mssillou, Aboul-Soud, Khalid, Hassani, Bousta, Achour, Benhida and Daoud.)

Alpinia galanga (L.) Willd. ( A. galanga ) is extremely significant and is utilized extensively in traditional medicine throughout many nations. This study aimed to determine the chemical composition of A. galanga rhizome extract (AgRE) and to evaluate its antioxidant, anticancer, and antibacterial activities. The total phenolic content (TPC) and total flavonoid content (TFC) of AgRE were determined. The antioxidant activity, cytotoxic capability, and antibacterial of were assessed, as well as anti-apoptotic genes. Molecular docking (MD) was used to assess the binding affinity of the most enriched constituents in AgRE toward the active sites of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and p53 tumor suppressor protein (TP53). Gas chromatography-mass spectrometry (GC-MS) analysis demonstrated that AgRE is a rich source of turmerone. AgRE had moderate 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging properties, with the half-maximal inhibitory concentration (IC 50 ) values of 79.34 ± 1.78 and 88.94 ± 2.28 μg/ml, respectively. AgRE preferentially reduced the viability of a subset of malignant MCF-7 and HepG2 cell lines, with IC 50 of 125.35 ± 4.28 and 182.49 ± 3.19 μg/ml, respectively. AgRE exhibited considerable antimicrobial activity against all bacterial strains, with MIC values ranging from 7.81 ± 1.53 to 62.5 ± 3.28 μg/ml. The MD results revealed that ethyl-4-(2-methylpropyl)-benzene had the greatest binding energy with NADPH oxidase, with a Glide score of -6848 kcal/mol, followed by 2-methoxy-phenol (-5111 kcal/mol). Taken together, we report the interesting antioxidant, antibacterial, and anticancer properties of AgRE, which warrant further investigation. AgRE is a promising natural resource that could be used to combat complicated diseases such as cancer and bacterial infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: Protein kinases (PKs) play key roles in cellular signaling and regulation cascades and therefore are listed among the most investigated enzymes with the intent to develop drugs that are able to modulate their catalytic features. Specifically, PKs are involved in chronic diseases of large impact in the society such as cancers and neurodegeneration. Since the approval of Fasudil for the management of cerebral vasospasm, frantic efforts are currently ongoing for the development of selective PK-modulating agents., Areas Covered: A selection of the most relevant patents in the European Patent Office for biomedical innovation and/or industrial development covering the years 2020-2023 on PK modulators either of the antibody and small-molecule type is reported. In addition to the examined patents, we also reported the contributions claiming the use of antibody-targeted PKs for lab bench identification kits., Expert Opinion: The field of PK modulators for biomedical purposes is particularly crowded with contributions, making it rich in valuable information for the development of potential drugs. An emerging frontier is represented by PK activators that aims to complement the use of PK inhibitors with the final intent of finely adjusting any PK-related disruption responsible for triggering any disease.

The main objective of the study is to evaluate the antioxidant, anticancer, and antimicrobial activities of Anchusa officinalis L. in vitro and in silico. The dried aerial parts of A. officinalis L. were extracted with methanol. Total phenolic and flavonoid content was analyzed. Antioxidant and antimicrobial effects were tested against both gram-positive and gram-negative bacteria. Gas chromatography-mass spectrometry analysis revealed the presence of 10 phytochemical compounds, and cyclobutane (26.07%) was identified as the major photochemical compound. The methanol extract exhibited the maximum amount of total phenolic content (118.24 ± 4.42 mg QE/g dry weight of the dry extract) (R 2  = 0.994) and the total flavonoid content was 94 ± 2.34 mg QE/g dry weight of the dry extract (R 2  = 0.999). The IC 50 value for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid was 107.12 ± 3.42 μg/mL, and it was high for 1,1-diphenyl-2-picryl hydrazyl (123.94 ± 2.31 μg/mL). The IC 50 value was 72.49 ± 3.14 against HepG2 cell lines, and a decreased value was obtained (102.54 ± 4.17 g/mL) against MCF-7 cell lines. The methanol extract increased the expression of caspase mRNA and Bax mRNA levels when compared to the control experiment (p < .05). The conclusions, A. officinalis L. aerial parts extract exhibited antibacterial, antifungal, and antioxidant activities., (© 2024 John Wiley & Sons Ltd.)

Anemia is a widespread global health concern necessitating effective, accessible, and natural interventions. The potential of medicinal plants to address anemia has garnered significant interest. Among these plants, parsley ( Petroselinum crispum ( Petroselinum crispum ) L.) stands out as an edible and herbal-based option for combating anemia. Aim of the study: This study investigated the potential of P. crispum (PC-Ext) as an emerging antianemic product, focusing on its physicochemical attributes, antioxidant properties, and mineral profile. Both qualitative and quantitative analyses of the phenolic compounds in P. crispum were conducted by using high-performance liquid chromatography with a diode array detector (HPLC-DAD). Anemia was induced in rats by intravenous injections of phenylhydrazine, administered at a dose of 40 mg/kg for two consecutive days. The antianemic activity of PC-Ext was assessed at a dose of 500 mg/kg twice daily for 5 weeks by estimating blood parameters, such as serum iron and ferritin. Additionally, the osmotic fragility test measured the capacity of red blood cells to withstand osmotic shock of various concentrations of saline. Aqueous extract of P. crispum was rich in phytochemical compounds, including syringic acid, quercetin, catechin, gallic acid, and luteolin. The findings demonstrate the effectiveness of P. crispum in ameliorating phenylhydrazine-induced reductions in red blood cell count (RBCs), hemoglobin (Hb), and hematocrit (HCT) levels. Consequently, PC-Ext exhibits significant activity against phenylhydrazine-induced anemia in rats, as demonstrated by its ability to prevent hemolysis. Iron estimation within PC-Ext further confirms its utility in addressing both iron deficiency and ferritin-deficiency anemia. Therefore, PC exhibits a favorable effect against both types of anemia, iron deficiency, and hemolysis. The results of this study provide robust scientific validation for ethnomedicinal use and the potential utility of P. crispum , positioning it as a promising source for future pharmaceutical development., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: This study investigates the potential effects of cannabis seed oil (CSO) on the wound healing process. The aim was to assess the efficacy of CSO in treating skin wounds using an animal model and to explore its anti-inflammatory properties through in silico analysis., Methods: Eighteen male albino Wistar rats, weighing between 200 and 250 g, were divided into three groups: an untreated negative control group, a group treated with the reference drug silver sulfadiazine (SSD) (0.01 g/mL), and a group treated topically with CSO (0.962 g/mL). The initial wound diameter for all groups was 1 cm. In silico studies were conducted using Maestro 11.5 to evaluate the anti-inflammatory effects of phytoconstituents against cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)., Results: CSO and SSD treatments led to a significant reduction (p <0.05) in the size of burned skin wounds by day 5, with contraction rates of 53.95% and 45.94%, respectively, compared to the untreated negative control group. By day 15, wounds treated with CSO and SSD had nearly healed, showing contraction rates of 98.8% and 98.15%, respectively. By day 20, the wounds treated with CSO had fully healed (100%), while those treated with SSD had almost completely healed, with a contraction rate of 98.97%. Histological examination revealed granulated tissue, neo-blood vessels, fibroblasts, and collagen fibers in wounds treated with CSO. In silico studies identified arachidic acid, γ-linolenic acid, and linolenic acid as potent inhibitors of COX-1 and COX-2. Serum biochemical parameters indicated no significant changes (p > 0.05) in liver and kidney function in rats treated with CSO, whereas a significant increase (p < 0.01) in ALAT level was observed in rats treated with SSD., Discussion: The findings demonstrate that CSO has a promising effect on wound healing. The CSO treatment resulted in significant wound contraction and histological improvements, with no adverse effects on liver and kidney function.However, the study's limitations, including the small sample size and the need for detailed elucidation of CSO's mechanism of action, suggest that further research is necessary. Future studies should focus on exploring the molecular pathways and signaling processes involved in CSO's pharmacological effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bouarfa, Chebaibi, Ez-Zahra Amrati, Souirti, Saghrouchni, El atki, Bekkouche, Mourabiti, Bari, Giesy, Mohany, Al-Rejaie, Aboul-Soud and Bousta.)

Although giant fennel is recognized as a "superfood" rich in phytochemicals with antioxidant activity, research into the antibacterial properties of its fruits has been relatively limited, compared to studies involving the root and aerial parts of the plant. In this study, seven solvents-acetone, methanol, ethanol, ethyl acetate, chloroform, water, and hexane-were used to extract the chemical constituents of the fruit of giant fennel (Ferula communis), a species of flowering plant in the carrot family Apiaceae. Specific attributes of these extracts were investigated using in silico simulations and in vitro bioassays. High-performance liquid chromatography equipped with a diode-array detector (HPLC-DAD) identified 15 compounds in giant fennel extract, with p-coumaric acid, 3-hydroxybenzoic acid, sinapic acid, and syringic acid being dominant. Among the solvents tested, ethanol demonstrated superior antioxidant activity and phenolic and flavonoid contents. F. communis extracts showed advanced inhibition of gram-negative pathogens (Escherichia coli and Proteus mirabilis) and variable antifungal activity against tested strains. Molecular docking simulations assessed the antioxidative, antibacterial, and antifungal properties of F. communis, facilitating innovative therapeutic development through predicted compound-protein interactions. In conclusion, the results validate the ethnomedicinal use and potential of F. communis. This highlights its significance in natural product research and ethnopharmacology., (© 2024. The Author(s).)

The bioactive extracts of traditional medicinal plants are rich in polyphenols and help to rejuvenate skin. The study was designed to assess the skin rejuvenating effects of a stable cream enriched with 4% I. argentea (IaMe) extract. The quantity of polyphenols by spectrophotometric methods was TPC, 101.55 ± 0.03 mg GAE/g and total flavonoid content; 77.14 ± 0.13 mg QE/g, while HPLC-PDA revealed gallic acid; 4.91, chlorogenic acid 48.12, p-coumaric acid 0.43, and rutin 14.23 μg/g. The significant results of biological activities were observed as DPPH; 81.81% ± 0.05%, tyrosinase; 72% ± 0.23% compared to ascorbic acid (92.43% ± 0.03%), and kojic acid (78.80% ± 0.19%) respectively. Moreover, the promising sun protection effects Sun protection factor of extract (20.53) and formulation (10.59) were observed. The active cream formulation (w/o emulsion) was developed with liquid paraffin, beeswax, IaMe extract, and ABIL EM 90, which was stable for 90 days as shown by various stability parameters. The rheological results demonstrated the active formulation's non-Newtonian and pseudo-plastic characteristics and nearly spherical globules by SEM. The IaMe loaded cream was further investigated on human trial subjects for skin rejuvenating effects and visualized in 3D skin images. Herein, the results were significant compared to placebo. IaMe formulation causes a substantial drop in skin melanin from -1.70% (2 weeks) to -10.8% (12 weeks). Furthermore, it showed a significant increase in skin moisture and elasticity index from 7.7% to 39.15% and 2%-30%, respectively. According to the findings, Indigofera argentea extract has promising bioactivities and skin rejuvenating properties, rationalizing the traditional use and encouraging its exploitation for effective and economical cosmeceuticals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Arshad, Shoaib Khan, Khan, Al-Roujayee, Mohany, Ahmad, Maryam, Akram, Shaukat, Khursheed and Aboul-Soud.)

Introduction: Epilepsy is a chronic brain disease characterized by repeated seizures and caused by excessive glutamate receptor activation. Many plants are traditionally used in the treatment of this disease. This study aimed to evaluate the bioavailability of a polyphenolic extract obtained from Origanum majorana L. (OMP) leaves, as well as its antiepileptic activity and its potential mechanism of action. Methods: We have developed and validated a simple, rapid, and accurate stability-indicating reversed-phase liquid chromatographic method for the simultaneous determination of caffeine and quercetin in rat plasma. The OMP antiepileptic effect was evaluated with pilocarpine-induced seizures, and a docking method was used to determine the possible interaction between caffeic acid and quercetin with the N-methyl-D-aspartate (NMDA) receptor. Results and Discussion: Both compounds tested showed low bioavailability in unchanged form. However, the tested extract showed an anticonvulsant effect due to the considerably delayed onset of seizures in the pilocarpine model at a dose of 100 mg/kg. The molecular docking proved a high-affinity interaction between the caffeic acid and quercetin with the NMDA receptor. Taken together, OLP polyphenols demonstrated good antiepileptic activity, probably due to the interaction of quercetin, caffeic acid, or their metabolites with the NMDA receptor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amaghnouje, Chebaibi, Aldossari, Ghneim, Amrati, Es-Safi, Di Cristo, Calarco, Achour, Carta, Al-Sheikh, Aboul-Soud and Bousta.)

Objective: To investigate the response of nutritional supplement (LNS-PLW) on appetite score, energy intake, insulin and glucose levels in preeclamptic women., Design & Participants: Sixty under-weight preeclamptic primigravida were divided into two groups randomly and provided LNS-PLW/Placebo in the fasted state. Blood samples were collected at fasting state, after 30mins of supplementation, "ad libitum buffet" breakfast and lunch for glucose and insulin levels., Results: Total energy intake was higher significantly in the LNS-PLW group, although during breakfast it was significantly reduced. The insulin and glucose concentration was significantly increased after 30min of supplementation in the LNS-PLW group., Conclusion: Intake of the LNS-PLW by pre-eclamptic women had short-term suppression on subsequent meal but improved total energy intake during trial., (Copyright 2024 The Author(s).)

Unpredictable chronic mild stress (UCMS) leads to variable metabolic effects. Oxidative stress (OS) of adipose tissue (AT) and mitochondrial energy homeostasis is little investigated. This work studied the effects of UCMS on OS and the antioxidant/redox status in AT and mitochondrial energy homeostasis in rats. Twenty-four male Wistar rats (180-220 g) were divided into two equal groups; the normal control (NC) group and the UCMS group which were exposed to various stresses for 28 days. An indirect calorimetry machine was used to measure volumes of respiratory gases (VO 2 & VCO 2 ), total energy expenditure (TEE), and food intake (FI). The AT depots were collected, weighed, and used for measuring activities and gene expression of key antioxidant enzymes (GPx1, SOD, CAT, GR, GCL, and GS), OS marker levels including superoxide anion (SA), peroxynitrite radical (PON), nitric oxide (NO), hydrogen peroxide (H 2 O 2 ), lipid peroxides (LPO), t-protein carbonyl content (PCC), and reduced/oxidized glutathione levels (GSH, GSSG). Additionally, AT mitochondrial fractions were used to determine the activities of the tricarboxylic acid cycle (TCA) cycle enzymes (CS, α-KGDH, ICDH, SDH, MDH), respiratory chain complexes I-III, II-III, IV, the nicotinamide coenzymes NAD + , NADH, and ATP/ADP levels. Compared with the NC group, the UCMS group showed very significantly increased OS marker levels, lowered antioxidant enzyme activities and gene expression, as well as lowered TCA cycle and respiratory chain activity and NAD + , NADH, and ATP levels (p < .001 for all comparisons). Besides, the UCMS group had lowered TEE and insignificant FI and weight gain. In conclusion, AT of the UCMS-subjected rats showed a state of disturbed redox balance linked to disrupted energy homeostasis producing augmentation of AT., (© 2023 John Wiley & Sons Ltd.)

This study was conducted to investigate the protective potential of a pharmaceutically formulated capsule of artichoke leaf powder (ArLP) against aflatoxin B 1 (AFB 1 )-induced hepatotoxicity in male albino rats. In the 42-day experiment, rats were divided into five equal groups: (i) control, treated with sterile water, (ii) treated with 4% DMSO as AFB 1 vehicle, (iii) ArLP of 100 mg kg -1 bw, (iv) AFB 1 of 72 µg kg -1 bw, and (v) AFB 1 plus ArLP. Exposure of rats to AFB 1 resulted in hepatotoxicity as manifested by the intensification of oxidative stress, production of free radicals and significant increase in the activity levels of liver function enzymes relative to the control. Significant reductions in both the enzymatic and non-enzymatic antioxidant markers as well as histopathological abnormalities in liver tissues were also observed. Notably, the combined administration of ArLP with AFB 1 clearly reduced AFB 1 -mediated adverse effects leading to the normalization of most of these parameters back to control levels. These findings clearly highlight the potential benefits of artichoke dietary supplements as a safe and natural solution in counteracting the adverse hepatotoxic effects conferred by AFB 1 exposure. Further research is warranted to fully dissect the biochemical and molecular mechanism of action of the observed artichoke-mediated hepatoprotection.

The goal of the current study is to achieve plant-mediated synthesis of iron oxide nanoparticles (Fe 2 O 3 NPs). The plant extract of Saccharum arundinaceum was used as a reducing and stabilizing agent for the synthesis of Fe 2 O 3 NPs. Different techniques such as energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy (UV-vis) were used to characterize the synthesis of Fe 2 O 3 NPs. UV-visible spectroscopy verified the synthesis of Fe 2 O 3 NPs using a surface plasmon resonance peak at a wavelength of 370 nm. SEM analysis specifies the spherical morphology of the synthesized nanoparticles with a size range between 30 and 70 nm. The reducing and capping materials of Fe 2 O 3 NPs were revealed by FT-IR analysis based on functional group identification. The plant extract contained essential functional groups, such as C-H, C-O, N-H, -CH 2 , and -OH, that facilitate the green synthesis of Fe 2 O 3 NPs. The EDX analysis detected the atomic percentage with the elemental composition of Fe 2 O 3 NPs, while the XRD pattern demonstrated the crystallinity of Fe 2 O 3 NPs. Furthermore, the synthesized Fe 2 O 3 NPs showed potential antiglycation activity under in vitro conditions, which was confirmed by the efficient zone of inhibition on glycation of bovine serum albumin/glucose (BSA-glucose) in the order <100 < 500 < 1000 μg/mL, which revealed that Fe 2 O 3 NPs showed significant antiglycation activity. Additionally, the cytotoxic activity against brain glioblastoma cells was assessed using the MTT assay, which exhibited diminished cytotoxic activity at concentrations lower than 300 μg/mL. Thus, we assumed that the resulting Fe 2 O 3 NPs are a good option for use in drug delivery and cancer treatments., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: patients with locally advanced breast cancer (LABC) are often treated by neoadjuvant chemotherapy (NACT). This study aims to determine the prevalence of psychological distress and their sociodemographic and clinical factors in patients recently diagnosed with LABC and before NACT., Methods: A total of 209 LABC patients without metastatic localization were recruited between 2021 and 2022 in the oncology hospital at Fez. A structured questionnaire and the Hospital Anxiety and Depression Scale were used. A descriptive analysis and linear model were performed., Results: a mean age of participants was 47.43 ± 9.45 years. The prevalence of depression, anxiety and psychological distress among participants was 59.62% (95% CI: 52.61-33.34), 47.85% (95% CI: 40.91-54.85), and 65.07 (95% CI: 58.19-71.52) respectively. Depression was associated to age (< 50 years) (AOR = 2.19; 95% CI = 1.13-4.23) and health insurance (AOR = 3.64; 95% CI: 1.18-11.26). Anxiety was associated to age (< 50) (AOR = 2.21; 95% CI: 1.18-4.13) and right breast cancer (AOA = 2.01; 95% CI: 1.11-3.65). Psychological distress was associated to chronic illness (AOR = 2.78; 95% CI: 1.32-5.85) and lymph node status (AOR = 2.39; 95% CI: 1.26-4.57)., Conclusions: Based on the high prevalence of depression and anxiety it appears opportune to treat psychological distress among LABC patient candidates for NACT. Each psychological intervention should take into account sociodemographic and clinical factors found associated in our study. Psychological therapeutic interventions are crucial for LABC patients as early as the time of diagnosis and through subsequent steps in NACT to improve their overall mental health., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Novel superparamagnetic iron oxide nanoparticles (SPIONs) of Methotrexate (MTX) were developed using supercritical liquid technology and optimized with a Box-Behnken design in order to assess its potential as a candidate for the treatment of breast cancer. MTX-SPIONs coated with poly(lactic- co -glycolic acid)-polyethylene glycol 400 had an aggregate size of 500 nm and an encapsulation efficiency of 46.8 ± 3.9%. The Fourier-transformed infrared spectroscopy analysis revealed a shift in the main bands due to intermolecular hydrogen bonds, whereas the differential scanning calorimetry analysis revealed the absence of the MTX melting endotherm, indicating complete encapsulation with oxide nanoparticles. The zeta potential results indicated a value of 4.98 mV, whereas the in vitro release study revealed an initial burst release followed by a considerable release of 35.1 ± 2.78% after 12 h. Using flow cytometry, control, MTX, and MTX-SPIONs were evaluated for apoptosis, with MTX-SPIONs exhibiting greater apoptosis than the control group and MTX. In addition, MTX-SPIONs inhibited cell division and content organization while substantially increasing the proportion of cells in the G1 and G2 phases relative to the control group. MTX-SPIONs exhibited prolonged anticancer effects against MCF-7 cell lines compared to MTX alone, indicating that SPION-delivered chemotherapeutics may increase cytotoxicity. The medication was stable with low encapsulated drug loss, suggesting that the supercritical liquid technology-based method is a promising way for generating drug-polymer magnetic composite nanoparticles for cancer treatment., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Bone formation is regulated by numerous factors, such as transcription factors, cytokines, and extracellular matrix molecules. Human hormone nuclear receptors (hHNR) are a family of ligand-regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various lipid-soluble signals, including retinoic acid, oxysterols, and thyroid hormone. We found that an hHNR called NR4A1 was the most highly expressed after human MSC differentiation into osteoblasts by whole-genome microarray. NR4A1 knockout decreased the osteoblastic differentiation of hMSCs in terms of ALPL expression and key marker gene expression. Whole-genome microarray analysis further confirmed the decrease in key pathways when we knocked down NR4A1. Further studies with small molecule activators identified a novel molecule called Elesclomol (STA-4783), which could activate and enhance osteoblast differentiation. Elesclomol activation of hMSCs also induced the gene expression of NR4A1 and rescued the phenotype of NR4A1 KD. In addition, Elesclomol activated the TGF-ß pathway by regulating key marker genes. In conclusion, we first identified the role of NR4A1 in osteoblast differentiation and that Elesclomol is a positive regulator of NR4A1 through activation of the TGF-ß signalling pathway., (© 2023 John Wiley & Sons Ltd.)

Global water consumption has grown twice as fast as the population. Wastewater is therefore a valuable and renewable source and provides additional water for priority uses. Wastewater can also be a source of pollution; thus, its physico-chemical and biological compositions can present major risks to the environment and human health. The objective of this study was to assess the status of irrigation waters in terms of salinization, accumulation of metallic elements, and microbiological contamination by parasites and pathogenic bacteria. The study focused on the surface water of Oued Fès used for irrigation located downstream of the industrial zone of Doukkarat and upstream of the industrial zone of Ain Noukbi (wastewater) before the confluence with the Oued Sebou, as well as on the treated wastewater of the wastewater treatment plant. The physico-chemical and microbiological analyses were carried out in two periods: summer and winter. Metals were analyzed by ICP-AES. The chemical and bacteriological quality of the wastewater and treated wastewater was found to be poor. These were characterized by organic pollution, including biodegradable pollutants, while upstream the organic residues were not biodegradables. COD, BOD 5 , Kjeldahl nitrogen, as well as chloride ion (Cl - ) are above the standard values. The highest concentrations of Cd, at 850 µg/l, Cu, at 690 µg/l and Mn, at 470 µg/l, largely exceed the international standards and requirements. In addition to fecal contamination, characterized by total coliforms and thermo-tolerant coliforms, other pathogens were present, including helminth eggs, both in the wastewater and in the treated wastewater. Other pathogens, such as Vibrio cholera, were found at all three sites whether in winter or summer, with the exception of the downstream of Oued Fez in winter. As for Salmonella, it was present in treated wastewater during the winter only. The water used for irrigation upstream of Oued Fez and the treated wastewater have poor to very poor quality. Therefore, for a better use of these waters, it is necessary to ensure their regular treatment in order to minimize the impacts on the environment and human health., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The goal of the current study was to synthesize zinc oxide nanoparticles (ZnO-NPs) using ZnCl 2 .2H 2 O salt precursor and an aqueous extract of Nephrolepis exaltata (N. exaltata), which act as a capping and reducing agent. N. exaltata plant extract-mediated ZnO-NPs were further characterized by various techniques, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), UV-visible (UV-Vis), and energy-dispersive X-ray (EDX) analysis. The nanoscale crystalline phase of ZnO-NPs was analyzed by the XRD patterns. The FT-IR analysis revealed different functional groups of biomolecules involved in the reduction and stabilization of the ZnO-NPs. The light absorption and optical properties of ZnO-NPs were examined by UV-Vis spectroscopy at a wavelength of 380 nm. The spherical shape morphology of ZnO-NPs with mean particle size ranges between 60 and 80 nm was confirmed by SEM images. While the EDX analysis was used to identify the elemental composition of ZnO-NPs. Furthermore, the synthesized ZnO-NPs demonstrate potential antiplatelet activity by inhibiting the platelet aggregation induced by platelet activation factor (PAF) and arachidonic acid (AA). The results showed that synthesized ZnO-NPs were more effective in inhibiting platelet aggregation induced by AA with IC 50 (56% and 10 μg/mL) and PAF (63% and 10 μg/mL), respectively. However, the biocompatibility of ZnO-NPs was assessed in human lung cancer cell line (A549) under in vitro conditions. The cytotoxicity of synthesized nanoparticles revealed that cell viability decreased and the IC 50 was found to be 46.7% at a concentration of 75 μg/mL. The present work concluded the green synthesis of ZnO-NPs that was achieved by N. exaltata plant extract and showed good antiplatelet and cytotoxic activity, which demonstrates the lack of harmful effects making them more effective for use in pharmaceutical and medical fields to treat thrombotic disorders., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The green synthesis of nanoparticles using plant extract is a new method that can be used in various biomedical applications. Therefore, the green approach was an aspect of ongoing research for the synthesis titanium dioxide nanoparticles (TiO 2 NP) using the Solanum surattense aqueous plant extract, which acts as a stabilizing and reducing agent. The synthesis of TiO 2 NPs was confirmed by energy dispersive X-ray (EDX), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy (UV-vis) analyses. The excitation energy to synthesize TiO 2 NPs was identified through the UV-vis spectrophotometric analysis at a wavelength of 244 nm. Further, the FT-IR spectroscopy visualized different biomolecules like OH, C=O, C-H, and C-O that were present in an aqueous extract of the plant and were responsible for the stabilization of TiO 2 NPs. The crystallinity and phase purity of TiO 2 NPs were illustrated by the sharp peaks of the XRD pattern. The spherical morphology with sizes ranging from 10 to 80 nm was examined using SEM images. The elemental composition of TiO 2 NPs was revealed by the intensity and narrow widths of titanium and oxygen using EDX analysis. This report also explains the antiepileptic activity of TiO 2 NPs in a maximal electroshock-induced epileptic (MESE) and pentylenetetrazol (PTZ) model. The synthesized TiO 2 NPs showed maximum antiepileptic activity in the PTZ model, significantly decreasing the convulsions (65.0 ± 5.50 s) at 180 mg/kg in contrast to standard drug phenytoin, whereas the MESE model was characterized by the appearance of extensor, clonus, and flexion. The results showed that synthesized TiO 2 NPs significantly reduced the time spent in each stage (15.3 ± 0.20, 16.8 ± 0.25, and 20.5 ± 0.14 s) at 180 mg/kg as compared to control groups. Furthermore, the cytotoxicity of synthesized produced TiO 2 NPs demonstrated that concentrations ≤80 μg/mL were biologically compatible., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Breast cancer (BC) is the most common female cancer in terms of incidence and mortality worldwide. Tamoxifen (Nolvadex) is a widely prescribed, oral anti-estrogen drug for the hormonal treatment of estrogen-receptor-positive BC, which represents 70% of all BC subtypes. This review assesses the current knowledge on the molecular pharmacology of tamoxifen in terms of its anticancer and chemo-preventive actions. Due to the importance of vitamin E compounds, which are widely taken as a supplementary dietary component, the review focuses only on the potential importance of vitamin E in BC chemo-prevention. The chemo-preventive and onco-protective effects of tamoxifen combined with the potential effects of vitamin E can alter the anticancer actions of tamoxifen. Therefore, methods involving an individually designed, nutritional intervention for patients with BC warrant further consideration. These data are of great importance for tamoxifen chemo-prevention strategies in future epidemiological studies.

Withania adpressa Coss. ex is a plant used in traditional medications. Antioxidant, antibacterial, and antifungal properties of the essential oil from leaves of Withania adpressa Coss ex. (EOW) were investigated. EOW was extracted using a Clevenger apparatus, and its volatile compounds were characterized by GC-MS. Antioxidant potency was determined using DPPH, FRAP, and TAC assays. Antibacterial effects were determined vs. Escherichia coli , Klebsiella pneumonia , Staphylococcus aureus , and Streptococcus pneumonia ; while its antifungal efficacy was determined vs. Candida albicans , Aspergillus flavus , Aspergillus niger , and Fusarium oxysporum using the disc diffusion and minimum inhibitory concentration bioassays. A chromatographic analysis showed that EOW contained eight phytochemical compounds constituting 99.14% of the total mass of oil. Caryophyllene (24.74%), Longifolene (21.37%), δ-Cadinene (19.08%), and Carene (14.86%) were predominant compounds in EOW. The concentrations required to inhibit 50% of free radical (IC50) values of antioxidant activities of EOW were 0.031 ± 0.006 mg/mL (DPPH), 0.011 ± 0.003 mg/mL (FRAP), and 846.25 ± 1.07 mg AAE/g (TAC). Inhibition zone diameters of EOW vs. bacteria were 18.11 ± 0.5 mm ( E. coli ), 17.10 ± 0.42 mm ( S. aureus ), 12.13 ± 0.31 mm ( K. pneumoniae ), and 11.09 ± 0.47 mm ( S. pneumoniae ), while MIC values were 51 ± 3, 47 ± 5, 46 ± 3 and 31 ± 1 µg/mL, respectively. Inhibition zone diameters of EOW vs. fungi were 31.32 ± 1.32, 29.00 ± 1.5, 27.63 ± 2.10, and 24.51 ± s1.07 mm for A. flavus , C. albicans , F. oxysporum , and A. niger , respectively. MIC values were 8.41 ± 0.40, 28.04 ± 0.26, 9.05 ± 0.76, and 22.26 ± 0.55 µg/mL, respectively. Importantly, the highest dose of EOW (1 mg/mL) showed negligible (~5%) cytotoxicity against MCF-12, a normal human epithelial cell line derived from the mammary gland, thus underscoring its wide safety and selectivity against tested microbes. To sum it up, EOW has exhibited promising antioxidant and antimicrobial properties, which suggests potential to abrogate antibiotic resistance.

The present study investigated the antioxidant and antimicrobial activities as well as characterized the chemical composition of the essential oils (EO) isolated from Artemisia flahaultii (EOF). EOF was extracted using hydro-distillation, and the chemical composition of EOF was ascertained by gas chromatography coupled with mass spectrometry (GC/MS). To assess antioxidant capacity, three tests were used: the 2,2-diphenyl-1-picrylhydrazil (DPPH), the total antioxidant capacity (TAC) and the ferric-reducing antioxidant power (FRAP) test. The antimicrobial activity of EOF was investigated using the diffusion assay and minimal inhibitory concentration assays (MICs). By use of in silico structure-activity simulations, the inhibitory potency against nicotinamide adenine dinucleotide phosphate (NADPH), physicochemical characters, pharmaco-centric properties and absorption, distribution, metabolism, excretion (ADME) characteristics of EOF were determined. GC/MS analysis reveals 25 components majorly composed of D-Limonene (22.09%) followed by β-pinene (15.22%), O -cymene (11.72%), β-vinylnaphthalene (10.47%) and benzene 2,4-pentadiynyl (9.04%). The capacity of DPPH scavenging by EOF scored an IC50 of 16.00 ± 0.20 µg/mL. TAC revealed that the examined oils contained considerable amounts of antioxidants, which were determined to be 1094.190 ± 31.515 mg ascorbic acid equivalents (AAE)/g EO. Results of the FRAP method showed that EOF exhibited activity with EC50 = 6.20 ± 0.60 µg/mL. Values for minimal inhibitory concentration (MIC) against certain clinically important pathogenic bacteria demonstrate EOF's potent antibacterial activity. MIC values of 1.34, 1.79, and 4.47 μg/mL against E. coli , B. subtilis and S. aureus were observed respectively. EOF exhibited significant antifungal activities against two stains of fungi: F. oxysporum and C. albicans , with values of 10.70 and 2.23 μg/mL, respectively. Of the total, 25 essential oils were identified. 2,4-Di-tert-butylphenol and capillin were the most active molecules against NADPH. The ADME prediction revealed that EOF was characterized by useful physicochemical characteristics and pharmaco-centric properties. The findings of this study show that the EOF can be used as an alternative to treat microbial resistance. Based on the in silico studies, EOF can be used as an "eco-friendly" NADPH inhibitor.

The plant Brocchia cinerea (Delile) ( B. cinerea ) has many uses in traditional pharmacology. Aqueous (BCAE) and ethanolic extracts (BCEE) obtained from the aerial parts can be used as an alternative to some synthetic drugs. In vitro, DPPH, FRAP and TAC are three tests used to measure antioxidant efficacy. Antibacterial activities were determined against one Gram positive and two Gram negative strains of bacteria. The analgesic power was evaluated in vivo using the abdominal contortion model in mice, while carrageenan-induced edema in rats was the model chosen for the anti-inflammatory test; wound healing was evaluated in an experimental second degree burn model. The results of the phytochemical analysis showed that BCEE had the greatest content of polyphenols (21.06 mg AGE/g extract), flavonoids (10.43 mg QE/g extract) and tannins (24.05 mg TAE/g extract). HPLC-DAD reveals the high content of gallic acid, quercetin and caffeic acid in extracts. BCEE has a strong antiradical potency against DPPH (IC 50 = 0.14 mg/mL) and a medium iron reducing activity (EC 50 = 0.24 mg/mL), while BCAE inhibited the growth of the antibiotic resistant bacterium, P. aeruginosa (MIC = 10 mg/mL). BCAE also exhibited significant pharmacological effects and analgesic efficacy (55.81% inhibition 55.64% for the standard used) and the re-epithelialization of wounds, with 96.91% against 98.60% for the standard. These results confirm the validity of the traditional applications of this plant and its potential as a model to develop analogous drugs.

Background: The IL-12/IFN- γ axis pathways play a vital role in the control of intracellular pathogens such as Salmonella typhi ., Objective: The study is aimed at using whole exome sequencing (WES) to screen out genetic defects in IL-12/IFN- γ axis in patients with recurrent typhoid fever., Methods: WES using next-generation sequencing was performed on a single patient diagnosed with recurrent typhoid fever. Following alignment and variant calling, exomes were screened for mutations in 25 genes that are involved in the IL-12/IFN- γ axis pathway. Each variant was assessed by using various bioinformatics mutational analysis tools such as SIFT, Polyphen2, LRT, MutationTaster, and MutationAssessor., Results: Out of 25 possible variations in the IL-12/IFN- γ axis genes, only 2 probable disease-causing mutations were identified. These variations were rare and include mutations in IL23R and ZNFX I. Other pathogenic mutations were found, but they were not considered likely to cause disease based on various mutation predictors., Conclusion: Applying WES to the patient with recurrent typhoid fever detects variants that are not much important as other genes in the IL-12/IFN- γ axis. Results of the current study suggest that a large population sizes would be needed to examine the functional relevance of IL-12/IFN- γ axis genes with recurrent typhoid fever., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2023 Faaiz ul Hassan et al.)

Sex determination in the early developmental stages of dioecious crops is economically-beneficial. During this study, a human homology of SRY gene was successfully identified in dioecious crops. SRY gene sequences of date palm and jojoba were submitted to GenBank under the accession numbers KC577225 and MK991776, respectively. This is the first report regarding the novel sex-determination methodology of four dioecious plants (jojoba, date palm, papaya, and pistachios). SRY sex gene was found in all the tested dioecious plant and human samples. This novel approach is simple and of significant importance for breeders. It facilitates the unambiguous selection of jojoba and date palm female plants at an early age and reduces the plantation cost of cultivating non-productive male plants. This is a rapid sex-determination technique for dioecious plants and mammals at an early stage. This technique specifically targets the SRY sequence that has been comprehensively investigated in humans. The kit development for the SRY-based sex determination of various crops is in progress., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

The present work was designed to study the chemical composition and the antioxidant and antimicrobial properties of fruits (SFr) and leaf (SF) extracts from Solanum elaeagnifolium var. obtusifolium (Dunal) Dunal ( S. elaeagnifolium). The chemical composition was determined using HPLC-DAD analysis. Colorimetric methods were used to determine polyphenols and flavonoids. Antioxidant capacity was assessed with DPPH, TAC, and FRAP assays. Antimicrobial activity was assessed using disk diffusion and microdilution assays against two Gram (+) bacteria ( Staphylococcus aureus ATCC-6633 and Bacillus subtilis DSM-6333) and two Gram (-) bacteria ( Escherichia coli K-12 and Proteus mirabilis ATCC-29906), while the antifungal effect was tested vs. Candida albicans ATCC-1023. By use of in silico studies, the antioxidant and antimicrobial properties of the studied extracts were also investigated. HPLC analysis showed that both fruits and leaf extracts from S. elaeagnifolium were rich in luteolin, quercetin, gallic acid, and naringenin. Both SFr and SF generated good antioxidant activity, with IC 50 values of 35.15 ± 6.09 μg/mL and 132.46 ± 11.73 μg/mL, respectively. The EC 50 of SFr and SF was 35.15 ± 6.09 μg/mL and 132.46 ± 11.73 μg/mL, respectively. SFr and SF also showed a good total antioxidant capacity of 939.66 ± 5.01 μg AAE/and 890.1 ± 7.76 μg AAE/g, respectively. SFr had important antibacterial activity vs. all tested strains-most notably B. subtilis DSM-6333 and E. coli , with MICs values of 2.5 ± 0.00 mg/mL and 2.50 ± 0.00 mg/mL, respectively. SFr demonstrated potent antifungal activity against C. albicans , with an inhibition diameter of 9.00 ± 0.50 mm and an MIC of 0.31 ± 0.00 mg/mL. The in silico approach showed that all compounds detected in SFr and SF had high activity (between -5.368 and 8.416 kcal/mol) against the receptors studied, including NADPH oxidase, human acetylcholinesterase, and beta-ketoacyl-[acyl carrier protein] synthase.

A series of new heterocycle hybrids incorporating pyrazole and isoxazoline rings was successfully synthesized, characterized, and evaluated for their antimicrobial responses. The synthesized compounds were obtained utilizing N -alkylation and 1,3-dipolar cycloaddition reactions, as well as their structures were established through spectroscopic methods and confirmed by mass spectrometry. To get more light on the regioselective synthesis of new hybrid compounds, mechanistic studies were performed using DFT calculations with B3LYP/6-31G(d,p) basis set. Additionally, the results of the preliminary screening indicate that some of the examined hybrids showed potent antimicrobial activity, compared to standard drugs. The results confirm that the antimicrobial activity is strongly dependent on the nature of the substituents linked pyrazole and isoxazoline rings. Furthermore, molecular docking studies were conducted to highlight the interaction modes between the investigated hybrid compounds and the Escherichia coli and Candida albicans receptors. Notably, the results demonstrate that the investigated compounds have strong protein binding affinities. The stability of the formed complexes by the binding between the hybrid compound 6c , and the target proteins was also confirmed using a 100 ns molecular dynamics simulation. Finally, the prediction of ADMET properties suggests that almost all hybrid compounds possess good pharmacokinetic profiles and no signs of observed toxicity, except for compounds 6e , 6f , and 6g ., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Bioprospecting natural products to find prominent agents for medical application is an area of scientific endeavor that has produced many clinically used bioactive compounds, including anticancer agents. These compounds come from plants, microorganisms, and marine life. They are so-called secondary metabolites that are important for a species to survive in the hostile environment of its respective ecosystem. The kingdom of Plantae has been an important source of traditional medicine in the past and is also enormously used today as an exquisite reservoir for detecting novel bioactive compounds that are potent against hard-to-treat maladies such as cancer. Cancer therapies, especially chemotherapies, are fraught with many factors that are difficult to manage, such as drug resistance, adverse side effects, less selectivity, complexity, etc. Here, we report the results of an exploration of the databases of PubMed, Science Direct, and Google Scholar for bioactive anticancer phytochemicals published between 2010 and 2020. Our report is restricted to new compounds with strong-to-moderate bioactivity potential for which mass spectroscopic structural data are available. Each of the phytochemicals reported in this review was assigned to chemical classes with peculiar anticancer properties. In our survey, we found anticancer phytochemicals that are reported to have selective toxicity against cancer cells, to sensitize MDR cancer cells, and to have multitarget effects in several signaling pathways. Surprisingly, many of these compounds have limited follow-up studies. Detailed investigations into the synthesis of more functional derivatives, chemical genetics, and the clinical relevance of these compounds are required to achieve safer chemotherapy.

Nanotechnology is one of the most recent technologies. It is uncertain whether the production of small-size nanoparticles (NPs) can be achieved through a simple, straightforward, and medicinally active phytochemical route. The present study aimed to develop an easy and justifiable method for the synthesis of Ag, Au, and their Ag/Au bimetallic NPs (BNPs) by using Hippeastrum hybridum (HH) extract, and then to investigate the effects of Ag, Au, and their Ag/Au BNPs as antimicrobial and phytotoxic agents. Ag, Au, and their Ag/Au BNPs were characterized by UV-visible spectroscopy, FT-IR spectroscopy, XRD, EDX, and SEM analysis. XRD analysis conferring to the face of face-centered cubic crystal structure with an average size of 13.3, 10.72, and 8.34 nm of Ag, Au, and Ag/Au BNPs, respectively. SEM showed that Ag, Au, and Ag/Au BNPs had spherical morphologies, with calculated nano measurements of 40, 30, and 20 nm, respectively. The EDX analysis confirmed the composition of elemental Ag signal of the HH-AgNPs with 22.75%, Au signal of the HH-AuNPs with 48.08%, Ag signal with 12%, and Au signal with 38.26% of the Ag/Au BNPs. The Ag/Au BNPs showed an excellent antimicrobial efficacy against Gram-positive Staphylococcus aureus , Actinomycetes meriye , Bacillus cereus , Streptococcus pyogenes , Methicillin-resistant Staphylococcus aureus , Micrococcus luteus , Streptococcus pneumonia , and Gram-negative Klebsiella pneumonia , Escherichia coli , and Serratia marcescens bacterial strains, as well as against three fungal strains ( Aspergillus niger , Aspergillus fumigatus , and Aspergillus flavus ) compared to HH extract, HH-AgNPs, and HH-AuNPs. However, further investigations are recommended to be able to minimize potential risks of application.

Plant based insecticides are considered among the most economic and ecofriendly chemicals for the protection of plants and stored grains. The cowpea weevil ( Callosbruchus maculatus ) causes more than 90% damage to sored grains in three to six months. The current study investigates insecticidal potentials of five selected botanicals: Melia azedarach, Nicotiana rustica, Azadirachta indica , Nicotiana tabacum and Thuja orientalis. They are explored at six different concentrations (0.5, 1.0, 1.5, 2.0, 2.5 and 3.0%) against C. maculatus and compared to effects of distilled water which is used as a control. Toxicities of 3%(V/V) extracts of N. tabacum, N. rustica, A. indica and T. orientalis against C. maculatus were 100%, 86.11%, 80.56% and 72.22%, respectively. Maximum mortality was caused by N. tabacum and N. rustica (100%), followed by A. indica (82%), whereas minimum mortality was observed in T. orientalis (64%) at 2.5%. Several phytochemicals, alkaloids, saponins, diterphenes, phytosterol, flavonoids and phenols were identified in N. tabacum and N. rustica, while few were present in A. indica. Phytosterol was present in greatest abundance. Saponins were only detected in aqueous extracts of N. rustica and N. tabacum. Taken together, these results indicate the utility of N. tabacum , N. rustica and A. indica as potential botanicals to control pest beetle and cowpea weevil.

Phyto-natural products are deeply associated with ethno-medicinal practices with less or more scientific validation for curing many vital diseases. Thus, the present study was carried out to asses chemical constituents and bioactivities of Grantia aucheri Boiss at different growth stages (vegetative, flowering, and seeding). For this aim, the chemical composition of G. aucheri ethanolic extracts was analyzed by gas chromatography with mass spectrometry detection (GC-MS), their total phenolics, total flavonoids, total tannins, and total anthocyanins concentrations were also spectrophotometrically determined. Antifungal and antibacterial activities were determined against three pathogenic fungi and six human pathogenic bacteria. Furthermore, antioxidant activity (DPPH and ABTS scavenging) and anti-inflammatory activity (Human Red Blood Cell Stabilization Method) were evaluated. The highest content of total phenolics, total flavonoids, total tannins, and total anthocyanins were established in the extract of G. aucheri at its flowering stage. Such phyto-compounds as boranyl acetate, β-himachalene and himachalol were major compounds found among 34 chemical constituents identified. The best antioxidant, anti-inflammatory, antifungal, and antibacterial activities were also found for this extract. Its phytochemicals presented bactericidal activities, mainly against Staphylococcus aureus, Bacillus subtilis, and Streptococcus pyogenes along with moderate fungicidal activity, however, it was less effective than the first one. Apart from antioxidant, antimicrobial, and anti-inflammatory activities, chemical constituents of G. aucheri may be potential alternative biomedical applications to reduce synthetic chemicals drugs., Competing Interests: Declaration of competing interest The authors declare no financial or other conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Jambosa caryophyllus has been used in traditional phytotherapy as a treatment against infections. In the present work, essential oils extracted from clove buds ( Jambosa caryophyllus ) (EO-JC) were investigated for their composition, antifungal, and insecticidal properties. Extraction of EO-JC was performed by use of hydrodistillation using a Clevenger-type apparatus, and the EOs were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Antifungal activity of EO-JC was evaluated by the use of solid-state diffusion (disc method) and microdilution to determine the minimum inhibitory concentration (MIC), against three strains of fungus, Aspergillus niger , Aspergillus flavus, and Fusarium oxysporum . Insecticidal activity of EO-JC against the cowpea weevil, Callosobruchus maculatus , was determined to assess utility of EO-JC to control this pest. Several exposures including inhalation and contact were used to determine lethality, as well as the repulsion test was conducted at concentrations of 4, 8, 16, and 32  μ L EO-JC. Characterization of EO-JC by GC/MS revealed 34 compounds accounting for 99.98% of the mass of the extract. The predominant compound was eugenol (26.80%) followed by β -caryophyllene (16.03%) and eugenyl acetate (5.83%). The antifungal activity of EO-JC on solid media exhibited inhibitions in the range of 49% to 87%, and MIC was between 3.125 and 7.80  μ g EO-JC/mL. Insecticidal activity, as determined by the use of the inhalation test, and expressed as the LD 50 and LD 95 after 96 hours of exposure was 2.32 and 21.92  μ L/L air, respectively. In the contact test, a 96-hour exposure resulted in LD 50 and LD 95 of 5.51 and 11.05  μ L/L of air, respectively. EO-JC exhibited insecticidal activity against fungi and pest chickpea weevil., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Otmane Zouirech et al.)

Due to poor diagnosis breast cancer in women has emerged as the most common cause of death disease in developing countries. Medicinal plants have been used for thousands of years and can be useful in healthcare, especially in developing countries. Ethanol extracts of leaves of fire bush or arta ( Calligonum comosum; EECC), exhibited significant anticancer potencies against two breast cancer cell lines, MCF-7 and MDA 231. These in vitro effects of EECC indicated potential anticancer activities that were determined to be specific since minimal toxicity was recorded against MCF-12, a non-cancerous breast cell line used as a reference. EECC also induced cell cycle arrest in MCF-7 and MDA 231 as revealed by the increased proportions of sub-G1 cells. Fluorescence-activated cell sorter analysis (FACS), utilizing double staining by annexin V-FITC/propidium iodide, revealed that the observed cytotoxic effects were mediated via apoptosis and necrosis. FACS measurement of thegreater in fluorescence intensity, linked with oxidation of DCFH to DCF, revealed that apoptosis was attributable to production of free radicals. EECC-mediated apoptosis was further validated by observation of up-regulation in the "executioner" enzyme, caspase 3. The current findings reveal that EECC exhibits significant, selective cytotoxicity to breast cancer cells, that proceeds via the generation of ROS, which culminates in apoptosis. The anti-proliferative effects of EECC weres further verified by use of a structure-based, virtual screening between its major bioactive polyphenolic constituents and the apoptosis executioner marker enzyme, caspase-3. Based on their glide score values against the active site of caspase 3, some phyto-constituents present in EECC, such as DL-alpha-tocopherol and campesterol, exhibited distinctive, drug-like potential with no predicted toxicity to non-target cells. Taken together, the usefulness of natural phenolic and flavonoid compounds contained in Calligonum comosum were suggested to be potent anticancer agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumar, Alfhili, Bari, Ennaji, Ahamed, Bourhia, Chebaibi, Benbacer, Ghneim, Abudawood, Alghamdi, Giesy, Al-Sheikh and Aboul-Soud.)

Meningitis caused by Klebsiella pneumoniae and Pseudomonas aeruginosa has lately become a prevalent cause of the central nervous system (CNS) infection. Bacterial invasion into the subarachnoid space prompts the releasing mechanism of chemokines and pro-inflammatory cytokines. The present study aimed to compare K. pneumoniae and P. aeruginosa meningitis concerning the memory, pro-inflammatory mediators and brain histopathological changes at different time intervals in adult Albino rats. The animals were sacrificed at three time intervals comprising 5, 10 and 15 days after meningitis induction. Cerebrospinal fluid (CSF) culture, relative brain weights, complete blood analysis, biochemical markers, levels of cytokine, chemokine and brain-derived neurotrophic factor (BDNF), neurotransmitter acetylcholine esterase (AChE) activity, and the brain histopathology of the infected rats in comparison to those in the control group were assessed. There was a significant increase in the levels of pro-inflammatory cytokines and chemokines including TNF-α, IL-1β, IL-6 and AChE after 5 days of bacterial meningitis infection with both K. pneumoniae and P. aeruginosa . The histopathological analysis of the cerebral cortex in the P. aeruginosa meningitis model at different time intervals revealed abundant numbers of dilated and congested blood vessels with severe hemorrhage, cerebral infarct, intracellular and extracellular vacuoles, and gliosis. Fifteen days post infection, a significant reduction in the brain tissue weight was observed. The meningitis model employing P. aeruginosa exhibited more evident time-dependent severity compared to K. pneumoniae , which may advocate its validity as a simple and effective research model to study meningitis of the CNS. This model may be utilized for further investigation to ascertain the molecular and biological association between bacterial meningitis and the development of the pathophysiological hallmarks underlying Alzheimer's disease in preclinical and clinical setups. Clinical extrapolation based on studies employing animal disease models should be carefully interpreted.

Inflammation is pivotal to the pathogenesis of diabetes mellitus (DM), but pathological alterations of the neutrophil−lymphocyte ratio (NLR), an emerging inflammatory index in DM management, remains understudied. The aim of this study is to examine the relationship between NLR and glycemic control in the Saudi population. Gender, age, WBC count, and fasting blood glucose (FBG) were obtained from Al-Borg Medical Laboratories for 14,205 subjects. Means, prevalence, risk measures, and the diagnostic accuracy of elevated NLR and hyperglycemia (HG) were evaluated. Subjects with elevated NLR (>3) had significantly higher FBG (105.10 ± 0.33 vs. 114.0 ± 2.81) and NLR was significantly elevated in impaired fasting glycemia (IFG; 1.21 ± 0.01 vs. 1.25 ± 0.01) and HG (1.21 ± 0.01 vs. 1.39 ± 0.02). Elevations of NLR in HG but not in IFG persisted across all age groups except young males and elderly females. The prevalence of elevated NLR in hyperglycemic subjects was 4.12% compared to 2.16% in subjects with normal FBG. HG was more prevalent in subjects with elevated NLR (17.33% vs. 12.46%) who had a relative risk (RR) of 1.68 (95% CI = 1.38−2.06, p < 0.0001) and an odds ratio (OR) of 1.94 (95% CI = 1.48−2.56, p < 0.0001) to be hyperglycemic. Nevertheless, NLR failed to discriminate individuals with normal FBG from those with HG based on ROC curve analysis. Pathological fluctuations in NLR may serve as supportive evidence in DM management.

Centaurea calcitrapa has been intensively utilized in ethnomedicinal practices as a natural therapeutic recipe to cure various ailments. The current study aimed to chemically characterize ethanolic extract of C. calcitrapa (EECC) aerial parts (leaves and shoots) by use of gas chromatography-mass spectrometry analyses (GC-MS) and investigate its antioxidant and in vitro anticancer activities, elucidating the underlying molecular mechanism by use of flow cytometry-based fluorescence-activated cell sorting (FACS) and conducting in silico assessment of binding inhibitory activities of EECC major compounds docked to caspase-3. CG-MS profiling of EECC identified a total of 26 major flavonoids and polyphenolic compounds. DPPH and ABTS assays revealed that EECC exhibits potent antioxidant activity comparable to standard reducing agents. Results of the proliferation assay revealed that EECC exhibit potent, dose-dependent cytotoxic activities against triple-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell models, with IC50 values of 1.3 × 102 and 8.7 × 101 µg/mL, respectively. The observed cytotoxic effect was specific to studied cancer cells since EECC exhibited minimal (~<10%) cytotoxicity against MCF-12, a normal breast cell line. FACS analysis employing annexin V-FITC/propidium iodide double labeling demonstrated that the observed anti-proliferative activity against MCF-7 and MDA-MB-231 was mediated via apoptotic as well as necrotic signaling transduction processes. The increase in fluorescence intensity associated with DCFH oxidation to DCF, as reported by FACS, indicated that apoptosis is caused by generation of ROS. The use of caspase-3-specific fluorogenic substrate revealed a dose-dependent elevation in caspase-3 substrate-cleavage activity, which further supports EECC-mediated apoptosis in MCF-7 cells. The major EECC compounds were examined for their inhibitory activity against caspase-3 receptor (1HD2) using molecular docking. Three compounds exhibited the highest glide score energy of −5.156, −4.691 and −4.551 kcal/mol, respectively. Phenol, 2,6-dimethoxy established strong binding in caspase-3 receptor of hydrogenic type, with residue ARG 207 and of PI-PI stacking type with residue HIS 121. By contract, hexadecenoic acid showed 3 H-bond with the following residues: ASN 615, ASN 616a and THR 646. Taken together, the current findings reveal that EECC exhibits significant and specific cytotoxicity against breast cancer cells mediated by the generation of ROS and culminating into necrosis and apoptosis. Further investigations of the phytoconstituents-rich C. calcitrapa are therefore warranted against breast as well as other human cancer cell models.

Nigella sativa (NS) is a plant that has long been utilized in traditional medicine as a treatment for certain diseases. The aim of this work was to valorize the essential oil (EO) of this species by phytochemical analysis and antimicrobial and antioxidant evaluation. EO was extracted by hydrodistillation from the seeds of Nigella sativa (EO-NS). Phytochemical content of EO-NS was evaluated by use of gas chromatography coupled to mass spectrometry (GC-MS/MS). Antioxidant ability was in vitro determined by use of three assays: 2.2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing power (FRAP), and total antioxidant capacity (TAC) relative to two synthetic antioxidants: BHT and quercetin. Antimicrobial effect was evaluated against four clinically important bacterial strains ( Staphylococcus aureus , ATCC 6633; Escherichia coli , K12; Bacillus subtilis , DSM 6333; and Proteus mirabilis , ATCC 29906) and against four fungal strains ( Candida albicans , ATCC 10231; Aspergillus niger , MTCC 282; Aspergillus flavus , MTCC 9606; and Fusarium oxysporum , MTCC 9913). Fifteen constituents that accounted for the majority of the mass of the EO-NS were identified and quantified by use of GC-MSMS. The main component was O -cymene (37.82%), followed by carvacrol (17.68%), α -pinene (10.09%), trans-sabinene hydrate (9.90%), and 4-terpineol (7.15%). EO-NS exhibited significant antioxidant activity with IC 50 , EC 50 , and total antioxidant capacity (TAC) of 0.017 ± 0.0002, 0.1196 ± 0.012, and 114.059 ± 0.97 mg EAA/g, respectively. Additionally, EO-NS exhibited promising antibacterial activity on all strains under investigation, especially on E. coli K12 resulting in inhibition diameter of 38.67 ± 0.58 mm and a minimum inhibitory concentration (MIC) of 1.34 ± 0.00  μ g/mL. Also, EO-NS had significant antifungal efficacy, with a percentage of inhibition of 67.45 ± 2.31% and MIC of 2.69 ± 0.00  μ g/mL against F. oxysporum , MTCC 9913 and with a diameter of inhibition 42 ± 0.00 mm and MIC of 0.67 ± 0.00  μ g/mL against C. albicans . To minimize development of antibiotic-resistant bacteria, EO-NS can be utilized as a natural, alternative to synthetic antibiotics and antioxidants to treat free radicals implicated in microbial infection-related inflammatory reactions., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Otmane Zouirech et al.)

Attenuation of adverse effects of aflatoxin (AFB 1 ) in brains of B 1 rats by extracts of leaves of artichoke was studied. The active ingredients in extracts of leaves of artichoke, Cynara scolymus L., were determined by HPLC analysis. In the 42-day experiment, rats were exposed to either sterile water, 4% DMSO, 100 mg artichoke leaf extract/kg body mass, 72  μ g aflatoxin B 1 /kg body mass, or AFB 1 plus artichoke leaf extract. Neurotoxicity of AFB 1 was determined by an increase in profile of lipids, augmentation of plasmatic glucose and concentrations of insulin, oxidative stress, increased activities of cholinergic enzymes, and a decrease in activities of several antioxidant enzymes and pathological changes in brain tissue. Extracts of artichoke leaf significantly reduced adverse effects caused by AFB 1 , rescuing most of the parameters to values similar to unexposed controls, which demonstrated that adverse, neurotoxic effects caused by aflatoxin B 1 could be significantly reduced by simultaneous dietary supplementation with artichoke leaf extract, which itself is not toxic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Enas A. Ibrahim et al.)

Ozonated olive oil (OL) combines the therapeutic effects of both ozone and olive oil. However, it suffers from limited water solubility and poor transdermal permeation, which hinder its application in melanoma treatment. Nanocarrier host molecules, such as niosomes, were used to improve the water solubility, transdermal permeation, and anticancer effect of hydrophobic compounds. This study aims to design and optimize a niosomal vesicular nanoplatform loaded with OL (OL/NSs) to improve OL's skin permeation and anti-melanoma effect. In this regard, OL was prepared and characterized by evaluating its chemical properties (acid, peroxide, and iodine values) and fatty acid composition using gas chromatography. Then, OL/NSs were developed using the thin film hydration method employing cholesterol, Span 60, and Tween 60 at five different molar ratios. The optimized niosomes had an average diameter of 125.34 ± 13.29 nm, a surface charge of -11.34 ± 4.71 mV, and a spherical shape. They could entrap 87.30 ± 4.95% of the OL. OL/NSs showed a 75% sustained oil release over 24 h. The skin permeation percentage of OL/NSs was 36.78 ± 3.31 and 53.44 ± 6.41% at 12 and 24 h, respectively, three times higher than that of the free OL (11.50 ± 1.3 and 17.24 ± 2.06%, at 12 and 24 h, respectively). Additionally, the anticancer activity of the developed niosmal formulation, when tested on human melanoma cells (A375), was double that of the free OL; the IC 50 of the OL/NSs was 8.63 ± 2.8 μg/mL, and that of the free OL was 17.4 ± 3.7 μg/mL. In conclusion, the encapsulation of ozonated olive oil in niosomes enhanced its water solubility, skin permeation, and anticancer activity and thus may represent potent natural chemotherapy in treating melanoma.