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Abstract The phytochemical, nutritional, and biological features of wild carob pulp from Tanzight (TN), Ait-Waada (AW), and Tizi-ghnayn (TG) in Azilal were studied. The results of the study reveal that the carob pulp examined has a low-fat level. AW had the most total sugar (78.34 ± 3.00%), total reducing sugar (27.20 ± 2.89%), crude fiber (14.21 ± 1.23%), sucrose (24.303 ± 0.038%), sodium (153.7 ± 18.52 mg/kg), pH (5.599 ± 0.05), and total polyphenol content (4134.50 ± 17.91 mg GAE/100 g DW). TG has higher amounts of potassium (11373 ± 153.7 mg/kg), calcium (4345 ± 7.211 mg/kg), phosphorus (3551 ± 175.1 mg/kg), magnesium (1347 ± 52.43 mg/kg), fructose (7.635 ± 0.012%), and total flavonoids (1678.08 ± 24.05 mg RE/100 g DW). TN has the highest levels of crude protein (5.607 ± 0.047%), moisture (9.33 ± 0.57%), ash (4.16 ± 0.02%), glucose (2.956 ± 0.047%), and total condensed tannins (529.61 ± 6.76 mg CE/100 g DW). The ethanol extract derived from AW exhibited noteworthy antioxidant activity, as evidenced by its total antioxidant capacity (TAC) of 1245.83 ± 26.33 µg ascorbic acid equivalent /mg extract and IC50 values of 18.45 ± 1.41 µg/mL, 124.98 ± 5.21 µg/mL, and 24.87 ± 1.30 µmol/mL for 2,2-Diphenyl-1-picrylhydrazil (DPPH), beta carotene (β-Carotene), and 2,2’-azino-bis (3-éthylbenzothiazoline-6-sulfonate) (ABTS), respectively. Furthermore, AW has demonstrated significant antibacterial activity against a variety of bacterial and fungal strains using disc diffusion and broth dilution techniques. The analysed samples also demonstrated encouraging anti-cancer effects on MDA-MB-231, MDA-MB-436, and MCF-7 cancer cell lines. The biological activities were confirmed through molecular docking analysis, identifying naringin and quercetin 3-O-β-glucoside as related compounds. Additionally, ADME analyses have revealed that all the synthetic compounds examined in this study demonstrate high intestinal absorption, meet Lipinski’s criteria, indicating their potential suitability for oral drug development. Based on these findings, wild carob pulp from Azilal province may contain bioactive compounds and nutrients.

Abstract Citrobacter koseri causes infection in people who are immunocompromised. Without effective antibiotics, these infections can become severe and life-threatening, so effective drugs are essential to treat these infections. Utilizing subtractive genomics, 2699 ORFs were predicted and translated into amino acid sequences. Metabolic pathway analysis and subcellular localization helped define the roles of key bacterial proteins. Two druggable proteins, WP_012000829.1 and WP_275157394.1, were discovered as promising targets. Alpha Fold provided 3D structures, and a library of 1600 echinoderm metabolites was docked against these proteins, with Ampicillin, Levofloxacin, and Doxycycline as controls. Notably, CMNPD13085 and CMNPD15632 exhibited the highest binding affinities for WP_012000829.1 and WP_275157394.1, respectively. Molecular dynamics simulations and MM-GBSA binding free energy complemented docking results. However, acknowledging the reliance on computational validations, the study emphasizes the need for essential in-vitro research to transform these potential inhibitors into therapeutic drugs.

IntroductionCarrot (Daucus carota) is a nutrient-dense root vegetable, and carrot pomace is a by-product of the juice extraction procedure, which is recognized a source of phytochemicals and functional components. Almonds (Prunus dulcis) are packed with a decent amount of nutrients and bioactives.MethodsThis study investigates the utilization of carrot pomace powder (CPP) and almond powder (AP) as partial substitutes for straight grade white flour (SGWF) in cakes to enhance their nutritional value and sensory appeal, while reducing waste from carrot processing. The aim is to assess the effects of incorporating CPP (at 5%, 10%, and 15%) and AP (at 5%) on the chemical composition and properties of cakes.Results and discussionComparative analysis reveals that AP is rich in fat (13.8 ± 0.6%) and protein (31 ± 0.6%), while CPP excels in ash (5.0 ± 0.5%) and fiber (43.3 ± 3.3%) content. Furthermore, SGWF exhibits the highest moisture content. Water holding capacities for CPP and AP are 5.2 ± 0.2% and 5.0±0.1%, respectively, and oil holding capacities are 1.3 ± 0.1% and 1.8 ± 0.2%, respectively. Additionally, CPP contains higher levels of sodium, potassium, and calcium, while AP contains higher levels of magnesium, iron, and zinc compared to SGWF. The addition of CPP and AP increases the ash, fat, fiber, and protein contents of the cakes. Notably, cakes containing 80% SGWF, 15% CPP, and 5% AP show significantly higher total phenolic content (TPC) (125.5 ± 3.8 mg GAE/100 g), total flavonoid content (TFC) (58.4 ± 1.4 mg QE/100 g), and DPPH activity (17.6 ± 2.7%) compared to control cakes. Furthermore, a significant increment in mineral content is observed in cakes with high levels of CPP and AP. Sensory evaluations reveal high acceptance of cakes containing 15% CPP and 5% AP. In conclusion, this study suggests that the incorporation of CPP and AP into cakes can improve their nutritional profile, antioxidant activity, and sensory characteristics, offering a sustainable approach to bakery product development.

BackgroundWith the increasing global prevalence of type 2 diabetes (T2D) and obesity, there is a pressing need for novel therapeutic interventions. Lavandula stoechas, a medicinal plant traditionally used for various ailments, holds promise as a potential agent for T2D management, particularly in Morocco, where it is commonly used to treat diabetes. This study aims to evaluate the pharmacological potential of L. stoechas aqueous extract (AqLs) by assessing its lipase inhibition antioxidant and anti-inflammatory activities, identifying phenolic compounds, and examining its efficacy in reducing diabetic complications.MethodsThe pharmacological potential of L. stoechas aqueous extract was investigated using in vitro assays. The inhibitory effect on pancreatic lipase, antioxidant power (FRAP), and anti-inflammatory activity (albumin denaturation method) was assessed. High-performance liquid chromatography (HPLC) analysis identified phenolic compounds. Additionally, albumin glycation was evaluated by estimating fructosamine, carbonyl groups, and amyloid β-structures to assess efficacy in mitigating diabetic complications.ResultsThe extract demonstrated concentration-dependent inhibition of pancreatic lipase (IC50 = 0.132 ± 0.006 mg/mL), potent antioxidant activity (IC50 = 604.99 ± 1.01 μg/mL), and dose-dependent anti-inflammatory effects (IC50 = 207.01 ± 34.94 mg/mL). HPLC analysis revealed phenolic compounds: naringin (38.28%), syringic acid (25.72%), and cinnamic acid (15.88%) were the most abundant, with 4-hydroxybenzoic acid, hydrated catechin, and catechin ranging from 9.60% to 5.24%, and p-coumaric acid (1.73%). Furthermore, the extract inhibited albumin glycation and fructosamine production, suggesting efficacy in mitigating diabetic complications.ConclusionThese findings highlight the multifaceted pharmacological potential of L. stoechas aqueous extract in T2D management, suggesting that this plant can be highly beneficial for diabetic individuals.

ABSTRACT: Aflatoxin B1 (AFB1) is a significant pollutant found in food and feed, posing a threat to public health. The objective of this study was to assess the effect of Lactiplantibacillus plantarum (LACP) against AFB1 in growing rabbits by investigating growth, serum metabolites, immunity, antioxidant capacity, and inflammatory response. A total of 60 growing male rabbits (721.5 ± 2.68g) were allocated to 4 experimental groups. The control group receiving only a basal diet, the AFB1 group (0.3 mg AFB1/kg diet), the LACP group (1 × 109 cfu/g /kg diet), and the combination group (1 × 109 cfu/g + 0.3 mg AFB1/kg diet; AFB1+ LACP) for 8 wk. The administration of AFB1 alone significantly decreased the final body weight, body gain, and feed intake, while significantly increasing the feed conversion ratio (P < 0.05). A significant decline in total proteins and globulins, along with elevated levels of hepatic enzymes (AST, ALP, ALT, and GGT) and renal function markers (creatinine and uric acid), were observed in the AFB1-contaminated group (P < 0.05). Immunoglobulins (IgG and IgM) were significantly decreased, alongside a significant elevation of triglycerides, direct bilirubin, and indirect bilirubin in growing rabbits fed diets with AFB1 (P < 0.05). Supplementing the AFB1 diet with LACP restored the growth reduction, improved liver (AST, ALP, ALT, and GGT) and kidney (creatinine and uric acid) functions, and enhanced immune markers in rabbit serum (P < 0.05). Antioxidant indices (SOD, GSH, and CAT) were significantly decreased in the AFB1 group (P < 0.05). However, the addition of LACP to the AFB1-contaminated diets improved antioxidant capacity and malondialdehyde (MDA) and protein carbonylation (PC) in hepatic tissues of rabbits (P < 0.05). Serum interlukin-4 (IL-4) and interferon gamma (IFN‐γ) levels were significantly increased in the AFB1 group (P < 0.05), but the addition of LACP significantly reversed this elevation. AFB1 downregulated the expression of immune-inflammatory genes such Nrf2, IL-10, and BCL-2 genes, while up-regulating the caspase-3 (CASP3) gene (P < 0.05). Supplementing AFB1 diet with LACP significantly decreased the expression of immune-inflammatory genes (Nrf2, IL-10, and BCL-2) and reduced the expression of the apoptotic-related gene CASP3. This study highlights the potential of L. plantarum (1 × 109 cfu/g /kg diet) as a protective agent against AFB1 in growing rabbits by enhancing antioxidant and immune function and reducing apoptosis and inflammation pathways.

IntroductionLiver diseases represent a significant global health challenge, with primary causes including excessive alcohol consumption, infections, chemotherapy, and autoimmune disorders. Medicinal plants, due to their natural bioactive compounds, hold promise for developing effective treatments and preventive measures against liver ailments. This study aimed to document the use of herbal remedies in northeastern Morocco for liver diseases and correlate these uses with scientific evidence through a bibliometric analysis.MethodsAn ethnobotanical survey was conducted in remote communities of northeastern Morocco from October 2020 to January 2022. A total of 189 informants were interviewed using semi-structured questionnaires to gather information on local medicinal plants used for liver ailments. The data were analyzed using four ethnobotanical quantitative indices: use value (UV), familial use value (FUV), informant consensus factor (ICF), and fidelity level (FL). Additionally, a bibliometric analysis was performed to evaluate the scientific support for the ethnopharmacological uses documented.ResultsThe survey identified 45 plant species from 26 different families used in the treatment of liver diseases. The most frequently utilized species were Cuminum cyminum L. (UV = 0.1065), Allium sativum L. (UV = 0.1015), Salvia officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Ziziphus lotus (L.) Lam. (UV = 0.0457). The Apiaceae family showed the highest familial use value (FUV = 0.1066), followed by Alliaceae (FUV = 0.1015). Liver congestion had the highest informant consensus factor (ICF = 0.83), followed by hepatic colic (ICF = 0.80). Bibliometric analysis revealed that 61% of the plants identified had documented pharmacological effects related to liver health.DiscussionThe study demonstrates that traditional knowledge in northeastern Morocco encompasses a rich diversity of medicinal plants used to treat liver diseases. The high ICF values indicate a strong consensus among informants on the efficacy of these remedies. The correlation between ethnopharmacological use and scientific validation for a significant portion of these plants suggests their potential as reliable therapeutic agents for liver conditions. However, further scientific investigations are necessary to confirm their efficacy and safety in clinical settings. This research contributes valuable information for future studies on the therapeutic potential of these plants.ConclusionThis ethnobotanical survey provides a comprehensive database of medicinal plants used in northeastern Morocco for liver diseases. The findings highlight the potential of these plants in developing novel treatments for hepatic conditions, although further research is essential to substantiate their therapeutic claims.

IntroductionMelons are highly sought after worldwide due to their exquisite and delectable taste. However, the peels of these fruits, which are rich in phytochemicals and sustainable components for innovative culinary formulations, are often discarded as waste.MethodsThis study explored the phytochemistry and valorization of three melon fruit, i.e., canary melon (Cucumis melo, var. Fonzy), watermelon (Citrullus lanatus, var. Augusta), and muskmelon (Cucumis melo, var. Cantaloupe), peels in food applications by incorporating into wheat flour biscuits. Peels of fruits were separated, dried and powders were extracted with 70% ethanol.Results and discussionComparing the muskmelon fruit peel to the peels of the other two fruits, the muskmelon fruit peel had the significantly (p

IntroductionThe aim of this study was to evaluate the antioxidant, antimicrobial, and preservative efficacy of Thymus broussonetii Boiss. essential oil (EO) in a topically applied formulation using a challenge test.MethodsThe essential oil was extracted from the aerial part of T. broussonetii using hydrodistillation, and the obtained EO was further analyzed by gas chromatography/mass spectrometry (GC/MS). The antioxidant effect of the EO was evaluated using three methods: the inhibition of free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), β-carotene–linoleic acid, and the ferric reducing antioxidant power (FRAP) methods. The antimicrobial activity and the minimum inhibitory concentration (MIC) of this EO were assayed by the disk-diffusion method and the broth microdilution method, respectively. The preservative efficacy of T. broussonetii EO was assayed at 1% and 2% (v/w) in a topical cream formulation using a challenge test against standard-specific microorganisms recommended by the European Pharmacopoeia. Furthermore, the identified phytochemical compounds were docked for their effect on nicotinamide adenine dinucleotide phosphate oxidase, human casein kinase 1 alpha 1 (CSNK1A1), glycogen synthase kinase 3, Staphylococcus aureus nucleoside diphosphate kinase, Escherichia coli beta-ketoacyl-[acyl-carrier protein] synthase, Pseudomonas aeruginosa LasR ligand-binding domain, and sterol 14-alpha demethylase (CYP51) from Candida albicans. The ADME/toxicity was predicted by analyzing the absorption, distribution, metabolism, and excretion parameters.Results and discussionchemical composition of the EO revealed the presence of thymol (63.09%), p-cymene (11%), and γ-terpinene (8.99%) as the major components. The antioxidant assays revealed that the essential oil exhibited strong antioxidant activity, as indicated by the minimum inhibitory concentration IC50 (IC50 = 210 ± 0.3 μg/mL for the DPPH assay, IC50 = 145 ± 0.1 μg/mL for the β-carotene assay, and IC50 = 84 ± 0.21 μg/mL for the FRAP assay) when compared to quercetin and butylated hydroxytoluene (BHT) as controls. The investigated essential oil exhibited important antimicrobial activity against all the tested microorganisms, and the MICs of the EO against bacteria and fungi were 0.02%–1%. Moreover, the EO of T. broussonetii evaluated at 2% (v/w) in a cream formulation succeeded in satisfying the A criteria for preservation efficacy against S. aureus, E. coli, and Aspergillus brasiliensis but exhibited less efficacy against P. aeruginosa (1.78 log reduction in the number of CFU/g after 7 days of evaluation) and C. albicans (1.09 log reduction in the number of CFU/g after 14 days of evaluation) when compared to the synthetic preservative phenoxyethanol 1% (v/w). In silico results showed that the antimicrobial activity of T. broussonetii EO is mostly attributed to thymol, terpinen-4-ol, and aromadendrene, while the antioxidant activity is attributed to thymol. These results indicate that the EO of T. broussonetii possesses important antimicrobial and antioxidant properties and can, therefore, be used as a natural preservative ingredient in the cosmetic industry.

The escalation of many coronavirus variants accompanied by the lack of an effective cure has motivated the hunt for effective antiviral medicines. In this regard, 18 Saudi Arabian medicinal plants were evaluated for SARS CoV-2 main protease (Mpro) inhibition activity. Among them, Terminalia brownii and Acacia asak alcoholic extracts exhibited significant Mpro inhibition, with inhibition rates of 95.3 % and 95.2 %, respectively, at a concentration of 100 µg/mL. Bioassay-guided phytochemical study for the most active n-butanol fraction of T. brownii led to identification of eleven compounds, including two phenolic acids (1, and 2), seven hydrolysable tannins (3–10), and one flavonoid (11) as well as four flavonoids from A. asak (12–15). The structures of the isolated compounds were established using various spectroscopic techniques and comparison with known compounds. To investigate the chemical interactions between the identified compounds and the target Mpro protein, molecular docking was performed using AutoDock 4.2. The findings identified compounds 4, 5, 10, and 14 as the most potential inhibitors of Mpro with binding energies of −9.3, −8.5, −8.1, and −7.8 kcal mol−1, respectively. In order to assess the stability of the protein–ligand complexes, molecular dynamics simulations were conducted for a duration of 100 ns, and various parameters such as RMSD, RMSF, Rg, and SASA were evaluated. All selected compounds 4, 5, 10, and 14 showed considerable Mpro inhibiting activity in vitro, with compound 4 being the most powerful with an IC50 value of 1.2 µg/mL. MM-GBSA free energy calculations also revealed compound 4 as the most powerful Mpro inhibitor. None of the compounds (4, 5, 10, and 14) display any significant cytotoxic activity against A549 and HUVEC cell lines.

Enzymatic degradation of cellulosic biomass represents the most sustainable and environmentally friendly method for producing liquid biofuel, widely utilized in various commercial processes. While cellulases are predominantly produced by bacteria and fungi, the enzymatic potential of cellulase-producing yeasts remains significantly less explored. In this study, the yeast strain Trichosporon insectorum, isolated from the gut of the coprophagous beetle Gymnopleurus sturmii, was utilized for cellulase production in submerged fermentation. A central composite design was employed to optimize cellulase production, with substrate concentration, temperature, and pH as dependent variables. The highest CMCase activity of 0.71 IU/mL was obtained at 1% substrate concentration, pH 5, and an incubation temperature of 40 °C for 72 h of fermentation using cellulose as a carbon source. For FPase production, the high value was 0.23 IU/mL at 0.5% CMC, pH 6, and an incubation temperature of 40 °C for 72 h. After purification, the enzymes produced by T. insectorum represent 39% of the total proteins. The results of this study offer an alternative strategy for utilizing various carbon sources, both soluble (CMC, carboxymethylcellulose) and insoluble (cellulose), to efficiently produce cellulase for the degradation of lignocellulosic materials. This approach holds promising benefits for sustainable waste management.

The objective of this study was to evaluate the antioxidant, anti-inflammatory, and anticancer properties of thymol, carvacrol, and their equimolar mixture. Antioxidant activities were assessed using the DPPH, ABTS, and ORAC methods. The thymol/carvacrol mixture exhibited significant synergism, surpassing the individual compounds and ascorbic acid in DPPH (IC50 = 43.82 ± 2.41 µg/mL) and ABTS (IC50 = 23.29 ± 0.71 µg/mL) assays. Anti-inflammatory activity was evaluated by inhibiting the 5-LOX, COX-1, and COX-2 enzymes. The equimolar mixture showed the strongest inhibition of 5-LOX (IC50 = 8.46 ± 0.92 µg/mL) and substantial inhibition of COX-1 (IC50 = 15.23 ± 2.34 µg/mL) and COX-2 (IC50 = 14.53 ± 2.42 µg/mL), indicating a synergistic effect. Anticancer activity was tested on MCF-7, MDA-MB-231, and MDA-MB-436 breast cancer cell lines using the MTT assay. The thymol/carvacrol mixture demonstrated superior cytotoxicity (IC50 = 0.92–1.70 µg/mL) and increased selectivity compared to cisplatin, with high selectivity indices (144.88–267.71). These results underscore the promising therapeutic potential of the thymol/carvacrol combination, particularly for its synergistic antioxidant, anti-inflammatory, and anticancer properties against breast cancer. This study paves the way for developing natural therapies against breast cancer and other conditions associated with oxidative stress and inflammation, leveraging the synergistic effects of natural compounds like thymol and carvacrol.

The optimization of existing natural antioxidants that are highly effective is crucial for advancements in medicine and the food industry. Due to growing concerns regarding the safety of synthetic antioxidants, researchers are increasingly focusing on natural sources, particularly essential oils (EOs). Combining EOs might enhance antioxidant activity due to increased chemical diversity. This study investigates, for the first time, the antioxidant properties of EOs from Lavandula dentata, Rosmarinus officinalis, and Myrtus communis, both individually and in combination, using the augmented-simplex design methodology. The in vitro evaluation of the antioxidant activity was performed using DPPH and ABTS radical scavenging assays. Chromatography gas-mass spectrometry (CG-MS) revealed that 1,8-cineol (37.27%) and pinocarveol (12.67%) are the primary components of L. dentata; verbenone (16.90%), camphor (15.00%), and camphene (11.03%) are predominant in R. officinalis; while cineol (43.32%) is the main component of M. communis. The EOs showed varying scavenging activities against ABTS and DPPH radicals, with DPPH assay values ranging from 194.10 ± 3.01 to 541.19 ± 3.72 µg/mL and ABTS assay values ranging from 134.07 ± 1.70 to 663.42 ± 2.99 µg/mL. These activities were enhanced when the EOs were combined. The optimal antioxidant blend for DPPHIC50 consisted of 20% L. dentata, 50% R. officinalis, and 30% M. communis. For the highest ABTS radical scavenging activity, the best combination was 18% L. dentata, 43% R. officinalis, and 40% M. communis. These results highlight the potential of EO combinations as new natural formulations for use in cosmeceutical, food, and pharmaceutical sectors.

Schizophrenia, a global mental health disorder affecting approximately 1 % of the population, is characterized by neurotransmitter dysregulation, particularly dopamine, serotonin, and glutamate. Current antipsychotic therapies, despite their efficacy, are accompanied by adverse effects, which has motivated researchers to investigate more secure substitutes. This study examines the potential antipsychotic effects of esculetin, a natural coumarin derivative recognized for its wide-ranging pharmacological activities (anti-inflammatory, antioxidant, anti-pathogenic, anticancer, and neuroprotective), in animal model of schizophrenia induced by ketamine. In order to induce disease, acute and chronic ketamine administration was performed on Swiss albino mice, supplemented with esculetin (as the test substance) and clozapine (as the reference standard). Behavioral studies and biochemical assays were performed to evaluate positive, negative, and cognitive symptoms of schizophrenia, as well as antioxidant and oxidant levels in various brain regions. Esculetin demonstrated significant improvements in behavioral symptoms, attenuated oxidative stress and neuroinflammation, and modulated neurotransmitter levels. Afterwards, ELISA was performed to evaluate levels of schizophrenia biomarkers AChE, BDNF. Moreover, proinflammatory cytokines (IL-6 and TNF-α) and NF-κB were also determined. Histopathological parameters of under study brain parts i.e., hippocampus, cortex and striata were also assessed. Esculetin and clozapine significantly (***p

Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.

The heterocycle compounds, with their diverse functionalities, are particularly effective in inhibiting Janus kinases (JAKs). Therefore, it is crucial to identify the correlation between their complex structures and biological activities for the development of new drugs for the treatment of rheumatoid arthritis (RA) and cancer. In this study, a diverse set of 28 heterocyclic compounds selective for JAK1 and JAK3 was employed to construct quantitative structure-activity relationship (QSAR) models using multiple linear regression (MLR). Artificial neural network (ANN) models were employed in the development of QSAR models. The robustness and stability of the models were assessed through internal and external methodologies, including the domain of applicability (DoA). The molecular descriptors incorporated into the model exhibited a satisfactory correlation with the receptor-ligand complex structures of JAKs observed in X-ray crystallography, making the model interpretable and predictive. Furthermore, pharmacophore models ADRRR and ADHRR were designed for each JAK1 and JAK3, proving effective in discriminating between active compounds and decoys. Both models demonstrated good performance in identifying new compounds, with an ROC of 0.83 for the ADRRR model and an ROC of 0.75 for the ADHRR model. Using a pharmacophore model, the most promising compounds were selected based on their strong affinity compared to the most active compounds in the studied series each JAK1 and JAK3. Notably, the pharmacokinetic, physicochemical properties, and biological activities of the selected compounds (As compounds ZINC79189223 and ZINC66252348) were found to be consistent with their therapeutic effects in RA, owing to their non-toxic, cholinergic nature, absence of P-glycoprotein, high gastrointestinal absorption, and ability to penetrate the blood-brain barrier. Furthermore, ADMET properties were assessed, and molecular dynamics and MM/GBSA analysis revealed stability in these molecules.

Uterine fibroids (UF), most prevalent gynecological disorder, require surgery when symptomatic. It is estimated that between 25 and 35 percent of women wait until the symptoms have worsened like extended heavy menstrual bleeding and severe pelvic pain. These UF may be reduced in size through various methods such as medical or surgical intervention. Progesterone (prog) is a crucial hormone that restores the endometrium and controls uterine function. In the current study, 28 plant-based molecules are identified from previous literature and docked onto the prog receptors with 1E3K and 2OVH. Tanshinone-I has shown the best docking score against both proteins. The synthetic prog inhibitor Norethindrone Acetate is used as a standard to evaluate the docking outcomes. The best compound, tanshinone-I, was analyzed using molecular modeling and DFT. The RMSD for the 1E3K protein–ligand complex ranged from 0.10 to 0.42 Å, with an average of 0.21 Å and a standard deviation (SD) of 0.06, while the RMSD for the 2OVH protein–ligand complex ranged from 0.08 to 0.42 Å, with an average of 0.20 Å and a SD of 0.06 showing stable interaction. In principal component analysis, the observed eigen values of HPR-Tanshinone-I fluctuate between −1.11 to 1.48 and −1.07 to 1.25 for PC1 and PC2, respectively (1E3K), and the prog-tanshinone-I complex shows eigen values of −38.88 to −31.32 and −31.32 to 35.87 for PC1 and PC2, respectively (2OVH), which shows Tanshinone-I forms a stable protein–ligand complex with 1E3K in comparison to 2OVH. The Free Energy Landscape (FEL) analysis shows the Gibbs free energy in the range of 0 to 8 kJ/mol for Tanshinone-I with 1E3K and 0 to 14 kJ/mol for Tanshinone-I with the 2OVH complex. The DFT calculation reveals ΔE value of 2.8070 eV shows tanshinone-I as a stable compound. 1E3K modulates the prog pathway, it may have either an agonistic or antagonistic effect on hPRs. Tanshinone-I can cause ROS, apoptosis, autophagy (p62 accumulation), up-regulation of inositol requiring protein-1, enhancer-binding protein homologous protein, p-c-Jun N-terminal kinase (p-JNK), and suppression of MMPs. Bcl-2 expression can change LC3I to LC3II and cause apoptosis through Beclin-1 expression.

This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-one derivatives 5a–5o. The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a “click chemistry” approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including 1H NMR, 13C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of −9.9 and −9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski’s criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development.

Honey, with its varied and extensive characteristics, is a complex and diverse biological substance that has been used since ancient times. The aim of this study is to thoroughly characterize the physicochemical, phytochemical, and biological properties of four floral honey varieties from the Fez-Meknes region in Morocco, with the goal of promoting the valorization of Moroccan honey in skincare and cosmetic products. The analyses of their physicochemical characteristics encompass various parameters such as pH, acidity, density, water content, Brix index, conductivity, ash content, hydroxymethylfurfural (HMF) content, and color. The levels of polyphenols range from 22.1 ± 0.4 to 69.3 ± 0.17 mg GAE/100 g of honey, measured using the Folin–Ciocalteu method for polyphenol quantification. Additionally, the estimation of flavonoid quantities in 100 g of honey, conducted using the aluminum trichloride method, reveals values ranging from 3.6 ± 0.2 to 7.2 ± 0.6 mg QE. Furthermore, it is noteworthy that honey exhibits high levels of glucose and relatively low concentrations of proteins. The quantitative evaluation of antioxidant effects, carried out through the 2,2-diphenyl-1-picrylhydrazyl free-radical-scavenging method and the ferric-reducing antioxidant power (FRAP) method, highlights the strong antioxidant capacity of multifloral honey, characterized by low inhibitory concentration values (IC50 = 30.43 mg/mL and EC50 = 16.06 mg/mL). Moreover, all honey varieties demonstrate antibacterial and antifungal properties, with multifloral honey standing out for its particularly pronounced antimicrobial activity. The correlation analyses between phytochemical composition and antioxidant and antibacterial activities reveal an inverse relationship between polyphenols and IC50 (DPPH) and EC50 (FRAP) concentrations of honey. The correlation coefficients are established at R2 = −0.97 and R2 = −0.99, respectively. Additionally, a significant negative correlation is observed between polyphenols, flavonoids, and antifungal power (R2 = −0.95 and R2 = −0.96). In parallel, a marked positive correlation is highlighted between antifungal efficacy, DPPH antioxidant activity (R2 = 0.95), and FRAP (R2 = 0.92). These results underscore the crucial importance of phytochemical components in the beneficial properties of honey, meeting international quality standards. Consequently, honey could serve as a natural alternative to synthetic additives.

Sinomenine (SN) is a well-documented unique plant alkaloid extracted from many herbal medicines. The present study evaluates the wound healing potentials of SN on dorsal neck injury in rats. A uniform cut was created on Sprague Dawley rats (24) which were arbitrarily aligned into 4 groups receiving two daily topical treatments for 14 days as follows: A, rats had gum acacia; B, rats addressed with intrasite gel; C and D, rats had 30 and 60 mg/ml of SN, respectively. The acute toxicity trial revealed the absence of any toxic signs in rats after two weeks of ingestion of 30 and 300 mg/kg of SN. SN-treated rats showed smaller wound areas and higher wound closure percentages compared to vehicle rats after 5, 10, and 15 days of skin excision. Histological evaluation of recovered wound tissues showed increased collagen deposition, fibroblast content, and decreased inflammatory cells in granulated tissues in SN-addressed rats, which were statistically different from that of gum acacia-treated rats. SN treatment caused positive augmentation of Transforming Growth Factor Beta 1 (angiogenetic factor) in wound tissues, denoting a higher conversion rate of fibroblast into myofibroblast (angiogenesis) that results in faster wound healing action. Increased antioxidant enzymes (SOD and CAT), as well as decreased MDA contents in recovered wound tissues of SN-treated rats, suggest the antioxidant potentials of SN that aid in faster wound recovery. Wound tissue homogenates showed higher hydroxyproline amino acid (collagen content) values in SN-treated rats than in vehicle rats. SN treatment suppressed the production of pro-inflammatory cytokines and increased anti-inflammatory cytokines in the serum of wounded rats. The outcomes present SN as a viable pharmaceutical agent for wound healing evidenced by its positive modulation of the antioxidant, immunohistochemically proteins, hydroxyproline, and anti-inflammatory cytokines.

In recent years, there has been a focus on developing and discovering novel Bruton's tyrosine kinase (BTK) inhibitors, as they offer an effective treatment strategy for B-cell malignancies. BTK plays a crucial role in B cell receptor (BCR)-mediated activation and proliferation by regulating downstream factors such as the NF-κB and MAP kinase pathways. To address this challenge and propose potential therapeutic options for B-cell lymphomas, researchers conducted 2D-QSAR and ADMET studies on pyrrolopyrimidine derivatives that act as inhibitors of the BCR site in cytochrome b. These studies aim to improve and identify new compounds that could serve as more potent potential BTK inhibitors, which would lead to the identification of new drug candidates in this field.In our study, we used 2D-QSAR (multiple linear regression, multiple nonlinear regression, and artificial neural networks), molecular docking, molecular dynamics, and ADMET properties to investigate the potential of 35 pyrrolopyrimidine derivatives as BTK inhibitors. A molecular docking study and molecular dynamics simulations of molecule 13 over 10 ns revealed that it establishes multiple hydrogen bonds with several residues and exhibits frequent stability throughout the simulation period. Based on the results obtained by molecular modeling, we proposed six new compounds (Pred1, Pred2, Pred3, Pred4, Pred5, and Pred6) with highly significant predicted activity by MLR models. A study based on the in silico evaluation of the predicted ADMET properties of the new candidate molecules is strongly recommended to classify these molecules as promising candidates for new anticancer agents specifically designed to target Bruton's tyrosine kinase (BTK) inhibition.

The extraction of gum from natural raw materials is of increasing importance in various industries, including food, pharmaceuticals, and cosmetics, particularly due to their emulsifying properties and potential applications as stabilizers and thickeners. This study presents an insight on the influence of changing parameters like reagents and operating condition on yield and some properties of the flax (Linum usitatissimum L.) seed gum. The extraction conditions were meticulously examined using a full factorial design, highlighting the significant impact of pretreatment, seed preparation, and solvent selection on the extraction yield. A response surface methodology (RSM) was then applied to optimize the water/benzoic acid ratio of the pretreatment step, the ethyl alcohol/water ratio, and the medium pH of the extraction method, resulting in a maximum yield of 14.47%. Furthermore, detailed analyses of the chemical and emulsifying properties of the gum were conducted showing emulsifying capacities over 94%, offering promising application prospects, particularly in the food industry.

Trigonelline, an alkaloid found in the seeds of Trigonella foenum-graecum L. (fenugreek), has been recognized for its potential in treating various diseases. Notably, trigonelline has demonstrated a neuroprotective impact by reducing intrasynaptosomal calcium levels, inhibiting the production of reactive oxygen species (ROS), and regulating cytokines. Kainic acid, an agonist of kainic acid receptors, is utilized for inducing temporal lobe epilepsy and is a common choice for establishing kainic acid-induced status epilepticus, a widely used epileptic model. The neuroprotective effect of trigonelline in the context of kainic acid-induced epilepsy remains unexplored. This study aimed to induce epilepsy by administering kainic acid (10 mg/kg, single subcutaneous dose) and subsequently evaluate the potential anti-epileptic effect of trigonelline (100 mg/kg, intraperitoneal administration for 14 days). Ethosuccimide (ETX) (187.5 mg/kg) served as the standard drug for comparison. The anti-epileptic effect of trigonelline over a 14-day administration period was examined. Behavioral assessments, such as the Novel Object Recognition (NOR) test, Open Field Test (OFT), and Plus Maze tests, were conducted 2 h after kainic acid administration to investigate spatial and non-spatial acquisition abilities in rats. Additionally, biochemical analysis encompassing intrasynaptosomal calcium levels, LDH activity, serotonin levels, oxidative indicators, and inflammatory cytokines associated with inflammation were evaluated. Trigonelline exhibited significant behavioral improvements by reducing anxiety in open field and plus maze tests, along with an amelioration of memory impairment. Notably, trigonelline substantially lowered intrasynaptosomal calcium levels and LDH activity, indicating its neuroprotective effect by mitigating cytotoxicity and neuronal injury within the hippocampus tissue. Moreover, trigonelline demonstrated a remarkable reduction in inflammatory cytokines and oxidative stress indicators. In summary, this study underscores the potential of trigonelline as an anti-epileptic agent in the context of kainic acid-induced epilepsy. The compound exhibited beneficial effects on behavior, neuroprotection, and inflammation, shedding light on its therapeutic promise for epilepsy management.

Peptic ulcer disease is the greatest digestive disorder that has increased incidence and recurrence rates across all nations. Prangos pabularia (L.) has been well documented as a folkloric medicinal herb utilized for multiple disease conditions including gastric ulcers. Hence, the target study was investigation the gastro-protection effects of root extracts of Prangos pabularia (REPP) on ethanol-mediated stomach injury in rats. Sprague Dawley rats were clustered in 5 cages: A and B, normal and ulcer control rats pre-ingested with 1 % carboxymethyl cellulose (CMC)); C, reference rats had 20 mg/kg omeprazole; D and E, rats pre-supplemented with 250 and 500 mg/kg of REPP, respectively. After one hour, group A was given orally 1 % CMC, and groups B-E were given 100 % ethanol. The ulcer area, gastric acidity, and gastric wall mucus of all stomachs were determined. The gastric tissue homogenates were examined for antioxidant and MDA contents. Moreover, the gastric tissues were analyzed by histopathological and immunohistochemically assays. Acute toxicity results showed lack of any toxic effects or histological changes in rats exposed to 2 and 5 g/kg of REPP ingestion. The ulcer controls had extensive gastric mucosal damage with lower gastric juice and a reduced gastric pH. REPP treatment caused a significant reduction of the ethanol-induced gastric lacerations represented by an upsurge in gastric mucus and gastric wall glycoproteins (increased PAS), a decrease in the gastric acidity, leukocyte infiltration, positively modulated Bax and HSP 70 proteins, consequently lowered ulcer areas. REPP supplementation positively modulated oxidative stress (increased SOD, CAT, PGE2, and reduced MDA) and inflammatory cytokines (decreased serum TNF-α, IL-6, and increased IL-10) levels. The outcomes could be scientific evidence to back-up the folkloric use of A. Judaica as a medicinal remedy for oxidative stress-related disorders (gastric ulcer).

This work explored the activities of bergamot oil nano-emulsion (NBG) in modulating blood biochemical parameters, redox status, immunity indices, inflammation markers, semen quality, testicular changes and the expression of HSPs genes in stressed rabbit bucks. Twenty-four mature rabbit bucks (5 months) were randomly divided into three groups; control group (NBG0) received 1 ml of distilled water, while the other two groups received NBG orally at doses of 50 and 100 mg/kg (bw) twice a week. The present study's findings revealed that treated groups had lower values of total and direct bilirubin, triglyceride, lactate dehydrogenase, and creatinine compared with NBG0 group (p

The emergence of drug-resistant microorganisms presents a substantial global public health threat. The increase in pathogens resistant to commonly prescribed antibiotics underscores the urgent requirement to explore alternative treatment strategies. This study adopts a novel approach by harnessing natural resources, specifically essential oils (EO), to combat bacterial pathogenicity. The primary aim of this research was to analyze the chemical composition of the aerial part of the Matricaria aurea (M. aureas) EO and evaluate its potential for inhibiting quorum sensing (QS) and disrupting biofilm formation in Pseudomonas aeruginosa (P. aeruginosa). The gas chromatography-mass spectrometry (GCMS) analysis unveiled that α-bisabolol oxide A constituted the predominant portion, comprising 64.8% of the total, with β-bisabolene at 6.3% and α-farnesene at 4.8% following closely behind. The antibiofilm efficacy was observed at concentrations of 0.3, 0.15, and 0.08 mg/mL, demonstrating negligible effects on cell viability. Furthermore, the EO from M. aurea effectively inhibited the formation of P. aeruginosa biofilms by diminishing aggregation, hydrophobicity, and swarming motility. Significantly, the EO treatment resulted in a conspicuous decrease in the production of pyocyanin, rhamnolipid, and extracellular polymeric substances (EPS), along with a reduction in the enzymatic activity of protease and chitinase. The EO effectively hindered QS by disrupting QS mechanisms, resulting in a marked decline in the secretion of N-Acyl homoserine lactone (AHL) molecules and the expression of phazA1 and aprA genes. This investigation offers compelling evidence supporting the potential of M. aurea EO as a promising therapeutic candidate for addressing infectious diseases induced by biofilm formation.

This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe2+-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of cellular signals is speculated upon to proffer suitable therapeutics for metabolic stress disorder upon their inhibition. While we know little about therapeutics with flexible dual inhibitors for these protein targets, this study was designed to screen KAD-7’s (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) inhibitory potential for both protein targets. We induced oxidative hepatic damage via the incubation of hepatic tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. We achieved the treatment by incubating the hepatic tissues with KAD-7 under the same conditions. The catalase (CAT), glutathione (GSH), malondialdehyde (MDA), ATPase, and ENTPDase activity were all measured in the tissues. We predicted how the drug candidate would work against ATPase and ENTPDase targets using molecular methods. When hepatic injury was induced, there was a significant decrease in the levels of the GSH, CAT, and ENTPDase (p < 0.05) activities. In contrast, we found a noticeable rise in the MDA levels and ATPase activity. KAD-7 therapy resulted in lower levels of these activities overall (p < 0.05), as compared to the control levels. We found the compound to have a strong affinity for ATPase (−7.1 kcal/mol) and ENTPDase (−7.4 kcal/mol), and a better chemical reactivity than quercetin. It also met all drug-likeness parameters. Our study shows that KAD-7 can protect the liver from damage caused by FeSO4 by reducing oxidative stress and purinergic actions. Our studies indicate that KAD-7 could be developed as a therapeutic option since it can flexibly inhibit both ATPase and ENTPDase.

Red Sea represents one of the most remarkable marine ecosystems. However, it is also one of the world's least explored areas of marine biodiversity. The aims of this investigation were therefore, to isolate marine microorganisms from the seashore sediments and water in shallow region from west Yemen coast, to assess their antimicrobial potential, to identify the highly active isolate, and to purify and identify the bioactive compounds from it. In this regard, twenty-five bacterial strains have been isolated from twenty samples and tested for their antimicrobial ability against some pathogenic bacteria and yeast by using the agar disk diffusion and agar well diffusion assay. Out of the total 25 marine actinomycetes isolates only 13 exhibited interesting antimicrobial activity. The morphological, biochemical, and phylogenetic characteristics of the potential isolate 1S1 were compatible with their classification in the genus Streptomyces. The 16S rRNA gene sequences have shown that the isolate 1S1 clustered with Streptomyces longisporoflavus. The strain Streptomyces sp. 1S1 was cultivated and extracted with ethyl acetate. The GC–MS study of the extract indicated the presence of certain fatty acyl compounds e.g., tetradecanoic acid, 9-octadecenoic acid, hexadecanoic acid, and 9,12,15-octadecatrienoic acid. Using chromatographic techniques, three compounds were isolated and by spectroscopic methods e.g., IR, MS and NMR structurally elucidated. The three compounds were identified as a triacylglyceride, 9-octadecenoic acid, and hexadecanoic acid. The study reinforces the evidence of the potential of Streptomyces sp and the ability to produce several antimicrobial compounds.

A structural class of forty glycine transporter type 1 (GlyT1) inhibitors, was examined using molecular modeling techniques. The quantitative structure-activity relationships (QSAR) technology confirmed that human GlyT1 activity is strongly and significantly affected by constitutional, geometrical, physicochemical and topological descriptors. ADME-Tox in-silico pharmacokinetics revealed that L28 and L30 ligands were predicted as non-toxic inhibitors with a good ADME profile and the highest probability to penetrate the central nervous system (CNS). Molecular docking results indicated that the predicted inhibitors block GlyT1, reacting specifically with Phe319, Phe325, Tyr123, Tyr 124, Arg52, Asp475, Ala117, Ala479, Ile116 and Ile483 amino acids of the dopamine transporter (DAT) membrane protein. These results were qualified and strengthened using molecular dynamics (MD) study, which affirmed that the established intermolecular interactions for (L28, L30–DAT protein) complexes remain perfectly stable along 50 ns of MD simulation time. Therefore, they could be strongly recommended as therapeutics in medicine to improve memory performance.

Some fruiting body fungi, such as mushrooms, have valuable nutritional and medicinal properties. The present study aimed to report some mushroom species for the first time in several regions of Saudi Arabia: Abha, Al-Baha, Al-Taif, and Jeddah. Morphological and microscopic features, the internal transcribed spacer (ITS) region, and a Basic Local Alignment Search Tool (BLAST) analysis were studied to identify Crinipellis scabella, Parasola conopilea, Agrocybe pediades, Pyrofomes demidoffii, and Tulostoma fimbriatum in Al-Baha, and Conocybe macrospora, and Chlorophyllum palaeotropicum throughout Saudi Arabia. All mushrooms identified in this present work were Agaricomycotina mushrooms recorded for the first time in Saudi Arabia.

In the present investigation, the phenolic compounds of Solanum elaeagnifolium were identified, and the plant’s anti-lipase and anti-glycation effects on hemoglobin were discovered through in vitro experiments, as well as its short-term antihyperglycemic and anti-inflammatory effects. The chemical compound composition was detected using HPLC-DAD, the anti-lipase activity was tested in vitro using 4-nitrophenyl butyrate as a substrate, and the antiglycation activity of the plant extracts was also tested in vitro using a haemoglobin model. The antihyperglycemic effect was determined by inhibiting pancreatic α-amylase and α-glycosidase activity and performing an in vivo glucose tolerance test on normal rats, and the anti-inflammatory activity was determined by inducing paw inflammation with carrageenan. In both the SEFR (fruit) and SEFE (leaf) extracts, chromatographic analysis revealed the presence of quercetin 3-O-β-D-glucoside, rutin, and quercetin. SEFR inhibited the pancreatic lipase enzyme more effectively, with an IC50 of 0.106 ± 0.00 mg/mL. S. elaeagnifolium extracts demonstrated significant antiglycation activity, with 3.990 ± 0.23 mg/mL of SEFE and 3.997 ± 0.14 mg/mL of SEFR. When compared to positive and negative controls, plant extracts had very significant anti-diabetic and anti-inflammatory effects. The findings in this study and previous research on this plant encourage us to investigate other pharmacological activities of this plant besides its duiretic, cictrisant, and anti-ulcer activity.

Background and Objectives: HIV disease is recognized to cause inconsistencies in coagulation via various pathways during infection. Some studies have indicated that HIV-infected patients are prone to developing thrombocytopenia, thrombosis, or autoantibodies that may cause difficulties in diagnosis. This study is intended to measure the trend of coagulation parameters in Sudanese patients with HIV. Materials and Methods: A cross-sectional study was carried out in patients with HIV admitted to the Sudan National AIDS Program (SNAP) from January 2018 to December 2019. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), D-dimer (DD), hemoglobin (HB), total lymphocyte count (TLC), platelet count (PLT), and a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), were evaluated among HIV Sudanese patients. Results: Out of the 44 HIV patients included, 6 (13.6%) were found to have thrombotic thrombocytopenic purpura-like events and 12 (27.2%) had antiphospholipid antibodies, of whom 8 (66.6%) showed anticardiolipin antibody (1gG (75%) and IgM (25%)) and 4 showed lupus anticoagulants. The HB, TLC, and PLT values were found to be significantly lower in HIV patients than in control (p = 0.000, 0.000, and 0.050, respectively). The PT and ADAMTS13 values showed no significant difference between HIV patients and control (p = 0.613 and 0.266, respectively). The PTT, TT, and DD values were found to be augmented in HIV patients versus the control (p = 0.000). Conclusions: Thrombotic thrombocytopenic purpura-like events among HIV Sudanese patients were explored. In addition, antiphospholipid antibodies were strikingly seen in these patients. Additional research is anticipated to confirm these diagnoses.

Juncus acutus, acknowledged through its indigenous nomenclature “samar”, is part of the Juncaceae taxonomic lineage, bearing considerable import as a botanical reservoir harboring conceivable therapeutic attributes. Its historical precedence in traditional curative methodologies for the alleviation of infections and inflammatory conditions is notable. In the purview of Eastern traditional medicine, Juncus species seeds find application for their remedial efficacy in addressing diarrhea, while the botanical fruits are subjected to infusion processes targeting the attenuation of symptoms associated with cold manifestations. The primary objective of this study was to unravel the phytochemical composition of distinct constituents within J. acutus, specifically leaves (JALE) and roots (JARE), originating from the indigenous expanse of the Nador region in northeastern Morocco. The extraction of plant constituents was executed utilizing an ethanol-based extraction protocol. The subsequent elucidation of chemical constituents embedded within the extracts was accomplished employing analytical techniques based on high-performance liquid chromatography (HPLC). For the purpose of in vitro antioxidant evaluation, a dual approach was adopted, encompassing the radical scavenging technique employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the total antioxidant capacity (TAC) assay. The acquired empirical data showcase substantial radical scavenging efficacy and pronounced relative antioxidant activity. Specifically, the DPPH and TAC methods yielded values of 483.45 ± 4.07 µg/mL and 54.59 ± 2.44 µg of ascorbic acid (AA)/mL, respectively, for the leaf extracts. Correspondingly, the root extracts demonstrated values of 297.03 ± 43.3 µg/mL and 65.615 ± 0.54 µg of AA/mL for the DPPH and TAC methods. In the realm of antimicrobial evaluation, the assessment of effects was undertaken through the agar well diffusion technique. The minimum inhibitory concentration, minimum bactericidal concentration, and minimum fungicidal concentration were determined for each extract. The inhibitory influence of the ethanol extracts was observed across bacterial strains including Staphylococcus aureus, Micrococcus luteus, and Pseudomonas aeruginosa, with the notable exception of Escherichia coli. However, fungal strains such as Candida glabrata and Rhodotorula glutinis exhibited comparatively lower resistance, whereas Aspergillus niger and Penicillium digitatum exhibited heightened resistance, evincing negligible antifungal activity. An anticipatory computational assessment of pharmacokinetic parameters was conducted, complemented by the application of the Pro-tox II web tool to delineate the potential toxicity profile of compounds intrinsic to the studied extracts. The culmination of these endeavors underpins the conceivable prospects of the investigated extracts as promising candidates for oral medicinal applications.

Traditional otic drug delivery methods lack controlled release capabilities, making reverse gelatination gels a promising alternative. Reverse gelatination gels are colloidal systems that transition from a sol to a gel phase at the target site, providing controlled drug release over an extended period. Thermosensitive norfloxacin reverse gelatination gels were developed using a Quality by Design (QbD)-based optimization approach. The formulations were evaluated for their in vitro release profile, rheological behavior, visual appearance, pH, gelling time, and sol–gel transition temperature. The results show that the gelation temperatures of the formulations ranged from 33 to 37 °C, with gelling durations between 35 and 90 s. The drug content in the formulations was uniform, with entrapment efficiency ranging from 55% to 95%. Among the formulations, F10 exhibited the most favorable properties and was selected for a stability study lasting 60 days. Ex-vivo release data demonstrate that the F10 formulation achieved 95.6percentage of drug release at 360 min. This study successfully developed thermosensitive norfloxacin reverse gelatination gels using a QbD-based optimization approach. The selected formulation, F10, exhibited desirable properties in terms of gelling temperature, drug content, and release profile. These gels hold potential for the controlled delivery of norfloxacin in the treatment of ear infections.

Exclusive physicochemical and biological properties of carbon allotrope graphene have attracted the peer attention of researchers for the synthesis and development of newer topical remedies including films, scaffolds, microspheres, and hydrogels. Here, graphene nanoplatelets (GN) were embedded into a different ratio of polymeric ERL100/ERS100 solution and fabricated in the form of a scaffold through the electrospinning process. FTIR spectra displayed characteristic similar peaks present both in GN and GN-loaded scaffold owing to the compatibility of GN and polymeric mixture. XRD curve revealed a distinct GN peak at nearly 26° whereas from DSC/TGA thermal stability was observed between polymers and graphene nanoplatelets. FESEM images showed ultrathin architecture of GN-loaded scaffold in a range of 280 ± 90 nm. The fabricated scaffold exhibited hydrophilicity (contact angle 48.8 ± 2.8°) and desirable swelling index (646% in skin pH media) which were desired criteria for the scaffold for topical application. In vitro, antifungal activity was conducted through the broth microdilution method against different virulent dermatophytes i.e., Microsporum gypseum, M. canis, M. fulvum, and Trychophyton rubrum. For in vivo evaluation, T. rubrum inoculum was applied on the dorsal surface of each group of Swiss albino mice, and the degree and intensity of mycelial growth or erythema on skin surfaces was visually investigated. The study depicted complete signs of cure after 14 days of application of G3-loaded scaffold on the infected dorsal site. Hence graphene-loaded scaffold represented a possible alternative for the treatment of topical fungal infections caused by dermatophytes.

Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified, but the notable alleles responsible for reduced enzyme activity are CYP2C9*2 and CYP2C9*3. No pharmacogenetic data are available on CYP2C9*2 and CYP2C9*3 alleles in the Pakistani population. In Pakistan, pharmacogenetics, which examines the relationship between genetic factors and drug response, are in the early stages of development. We, for the first time, investigated the association between the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 and the incidence of hypoglycaemia in patients with Type 2 diabetes mellitus (T2DM) receiving sulphonylurea medications. A total of n = 400 individuals of Pashtun ethnicity were recruited from 10 different districts of Khyber Pakhtunkhwa, Pakistan to participate in the study. The study participants were divided into two distinct groups: the case group (n = 200) and the control group (n = 200). The case group consisted of individuals with T2DM who were receiving sulphonylurea medications and experienced hypoglycaemia with it, whereas the control group included individuals with T2DM who were receiving sulphonylurea medication but did not experience sulphonylurea-induced hypoglycaemia (SIH). Blood samples were obtained from study participants following informed consent. DNA was isolated from whole blood samples using a Wiz-Prep DNA extraction kit. Following DNA isolation, CYP2C9 alleles were genotyped using MassARRAY sequencing platform at the Centre of Genomics at the Rehman Medical Institute (RMI). The frequency of CYP2C9*2 (low-activity allele) was more frequent in the diabetic patients with SIH compared to the control group (17.5% vs. 6.0%, p = 0.021). The frequency of its corresponding genotype CYP2C9*1/*2 was higher in cases compared to the control group (10% vs. 6% with p = 0.036); the same was true for genotype CYP2C9*2/*2 (7% vs. 3.5% with p = 0.028). Logistic regression analysis evidenced potential association of CYP2C9*2 allele and its genotypes with SIH. When adjusted for confounding factors such as age, weight, sex, mean daily dose of sulphonylurea, and triglyceride level, the association between the CYP2C9*2 allele and hypoglycaemia remained consistent. Confounding factors played no role in SIH (insignificant p-value) because both groups (cases and controls) were closely matched in term of age, weight, sex, mean daily dose of sulphonylurea, and triglyceride levels. Our study suggests that genetic information about a patient’s CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug, based on their genetic make-up.

Parasites are a significant component of biodiversity. They negatively affect fish appearance, growth, and reproduction. In this study, the prevalence of infection, diversity, and mean intensity of parasites were examined in 9 freshwater fish species (45 samples per fish species). Ecto-parasites were examined on the skin, gills, and fins with a hand lens. Wet mounts were prepared using mucosal scrapings from all the external and internal organs of the sampled fish. Microscopy, muscle compression, and the pepsin-HCL artificial digestion technique were also performed. In this study, 26 species of parasites were identified including three taxa belonging to 9 species of protozoan parasites, 11 treamtodes, and 6 monogenean parasites. The identified protozoan parasites were Entamoeba histolitica, Chilodonella sp., Coccidia sp., Costia sp., Cryptobia sp., Ichthyopthiris-multifilis, Microsporidia, Piscinoodinium sp., and Ichthyobodo necator. The identified trematode parasites were Fasciola gigantica, Echinostoma revolutum, Fasciola hepatica, Haplorchis pumilio, Brachylaima cribbi, Echinostoma cinetorchis, Neascus sp., Deropegus sp., Trematode Soldier, Centrocestus formosanus, and Clinostomum marginatum. The identified monogenean parasites were Dactylogyrus limipopoensis, Dactylogyrus anchoratus, Dactylogyrus myersi, Dactylogyrus vastator, Gyrodactylus salaris, and Ancyrocephalus. The diversity of parasites was maximum at the Okara site. The host’s organs that were targeted for parasitic infection included the intestine, liver, gills, fins, skin, and kidneys. The majority of the parasites were identified in Labeo rohita followed by Hypophthalmichthys molitrix, Ctenopharyngodon idella, Oreochromis niloticus, Cyprinus carpio, and Wallagu attu. Two species appeared to be resistant species because none of the parasites were observed in Notopterus notopterus or Sperata seenghala. This study also concluded that the prevalence of parasites increased with increasing length, size, and age of fish.

Using different chromatographic methods, four new compounds were isolated from the aerial parts of Suaeda monoica (Chenopodiaceae) along with 2-hydroxy-1-naphthoic acid (SCM-3). The structures of the new compounds were established as 6′-hydroxy-10′-geranilanyl naphtha-1-oate (SMC-1), 4,4,8β,10β-Tetramethyl-9β-isobutanyl decalin-13-ol-13-O-β-D-xylopyranoside (SCM-2), 6′-(2-hydroxynaphthalen-3-yl) hexanoic acid (SCM-4) and 1′-(2-Methoxy-3-naphthyl)-4′-(2′'-methylbenzoyl)-n-butane (SMC-5) by IR, EIMS and NMR (1 & 2D) analyses. All compounds (50 μg/mL) were tested for cell proliferative potential on cultured human liver cell HepG2 cells by MTT assay. The results revealed a marked cell proliferative potential of all compounds (1.42–1.48 fold) as compared to untreated control. The results of molecular docking and binding with specific proteins such as PTEN (Phosphatase and Tensin homolog) and p53 also justify the cell proliferative potential of the isolated compounds. Glide program with Schrodinger suit 2018 was used to evaluate the binding between SMC compounds and proteins (PTEN and p53). The binding affinity of all compounds was in order of 104–105 M−1 towards both PTEN and p53. All the SMC compounds have been found to bind at the active site of PTEN, thereby may prevent the binding of phosphatidylinositiol 3,4,5-triphosphate (PI3P). In the locked position, PTEN would not be able to hydrolyze PI3P and hence the PI3P regulated signaling pathway remains active. Similarly, SMC molecules were found to interact with the amino acid residues (Ser99, Thr170, Gly199, and Asp224) which are critically involved in the formation of tetrameric p53. The blockage of p53 to attain its active conformation thus may prevent the recruitment of p53 on DNA and hence may promote cell proliferation. Keywords: Suaeda monoica, Cell-proliferation, Molecular docking, β-Naphthol, Caproic acid, Chenopodiaceae, HepG2 cells

Background: The insulin-responsive glucose transporter 4 (GLUT4) plays prominent role in insulin-mediated facilitated glucose uptake into most of the cell types, majorly muscle, liver and adipose tissue. Impaired expression of GLUT4 has been linked to insulin resistance and diabetes. In adipocytes, excess lipids that are generated from liver and by de novo lipogenesis utilizing blood sugar, are stored. There are various nuclear factors, co-factors and signaling mechanisms that directly and indirectly regulate glucose transporter activity in adipocytes. Molecular mechanism behind the regulation of GLUT4 in adipocytes has not elucidated well. Objective: Therefore, the present study focuses to explore the role of Liver X receptor- alpha (LXRα) on GLUT4 expression and the possible co-factors involved during in vitro adipogenesis and is assessed by modulating the activity of LXRα with specific agonist and antagonist ligands in 3T3L1 differentiated cells. Results: The results demonstrate that SR 9238 (300 nM), a strong inhibitor of LXRα, decreased the rate of adipogenesis through reduced lipid droplet formation in adipocytes without affecting the cell morphology. The FMOC-l-Leucine (FLL), a known partial ligand of PPARγ, enhanced the expression of LXRα. Thus, it can be concluded that LXRα has a significant role in adipocyte differentiation and FLL interaction promoted the transcription of LXRα, thereby promotes GLUT4 expression. The results in this study identified the role of LXRα in regulating the expression of GLUT4 through SRC1. Conclusion: The study is of much relevance in treatment of diabetes and also opens the possibility of identifying new drug molecules that target LXRα. Keywords: LXRα, Diabetes, GLUT4, PPARγ, Adipocyte, Insulin resistance

Chalcones, either natural or synthetic, are known to exhibit various biological activities. The present study aimed to evaluate the in vitro and in silico activities of some chalcone analogues as potential antleishmanial agents via inhibition of the trypanothione reductase enzyme (TR). Five chalcone analogues were synthesized using Claisen-Schmidt reaction and their activity has been evaluated against Leishmania donovani and presented as IC50 values. Various integrated web-based technologies were used to assess the synthesized compounds' absorption, distribution, metabolism, excretion, and toxicity profile (ADMET). The binding affinity of the most potent chalcone for the selected target was then investigated using Auto-Dock 4.0. Additionally, the molecular dynamics was performed using WEBGRO. (E)-1-(4-bromophenyl)-3-(4-hydroxyphenyl) prop-2-en-1-one (Chalcone 4) has shown the highest inhibitory effect with IC50 value 0.03 ± 0.16 µM. In addition, the pharmacokinetic and toxicological investigations revealed its good oral bioavailability and low toxicity. Furthermore, chalcone 4 was found to interact with high affinity (−8.6 kcal/mole) with trypanothione reductase (TR), an essential enzyme for the leishmanial parasite. Molecular dynamics simulation revealed several interesting features responsible for the potency and stability of chalcone 4 as TR inhibitor. Thus, the promising activity against Leishmania donovani, compared to amphotericin B and other reported chalcones derivatives, proposes the use of chalcone 4 as a potential new therapy for visceral leishmaniasis.

The current study focused on anti-biofilm property of chitosan loaded essential oils, which were obtained and evaluated against biofilm forming Acinetobacter baumannii. The results of agar well punctured method demonstrated its effeciency at 150 µg/mL concentration. The complete biofilm arrangement was demolished at 150 µg/mL concentration as suggested by quantitative invitro inhibition assay measurement. The biofilm metabolic cells lost their virulence, which was confirmed by color changes of XTT assay. Furthermore, the biofilm metabolic product inactivation was proved by congo red agar assay with the evidence of complete exopolysaccharide arrest. The interior and exterior portions of the chitosan loaded essential oils were completely damaged, as suggested by confocal laser scanning electron microscope and scanning electron microscope observations. Hence, all the invitro inhibition assays, and morphological examination confirmed that the biofilm forming Acinetobacter baumannii lost its virulence factors and its bacterial growth was eradicated efficiently.

Objective: Oxidative stress causes multidirectional damage including different types of cancers in our body by affecting the normal physiological functions of the cells and tissues. The objective is to study the cytotoxic and antioxidant potential of natural compounds isolated from fruits of Z. armatum DC. Methods: This study was designed to investigate the chemical nature as well as biological effects of natural compounds. The isolated compounds were tested for antioxidant effect in various ways e.g. DPPH free radical inhibition, ferric reducing effect, superoxide dismutase, and catalase evaluation. The cytotoxic effect of isolated compounds was evaluated using HepG2 cancer cells. Results: Chemical investigations on the fruits of Z. armatum DC, led to the isolation of two new compounds characterized as (cis)-2, 8-dimethyl-non-5-en-8-ol-2-olyl benzoate (1), (cis)-2, 10-dimethyl-undec-7-en-10-ol-2-olyl benzoate (2) along with five known compounds such as n-dodecanyl linoleniate (3), n-octacos-10, 20-dienoic acid (4), (cis, cis)-dotriacont-6, 12-dienoic acid (5), lignoceric acid (6), and (cis, cis)-dotriacont-6, 8-dienoic acid (7). Compound 1 shows potent activity against HepG2 cancer cells in comparison 2 and significantly affected the viability of cells till 48 hrs. The highest antioxidant potential among compounds and extracts with respect to DPPH free radical inhibition and the ferric reducing effect was shown by compound 1 followed by 2 and 7 with an EC50 value of 19.44, 20.44 and, 22.46 respectively. Conclusions: The present study indicates that compound (1) showed a significant effect against HepG2 cancer cells as well as antioxidant potential through DPPH and FRAP methods. Compounds 2 and 7 also proved to be useful up to some extent for antioxidant potential.

Background: Self-medication with antibiotics (SMA) is one of the common factors which precipitate antimicrobial resistance, yet if effective implementations are amended it can be effortlessly controlled. The present study aimed to estimate the prevalence and predictors of SMA in Sudan. Methods: The study adopted a cross-sectional study design conducted in all Sudan states between June and December 2021. Multi-stage stratified cluster sampling was used. A semi-structured questionnaire was used for data collection. Descriptive statistics were used to present the data. Binary logistic regression was computed to investigate the possible factors which associated with SMA. Results: Out of 1492 participants surveyed, 71.3% utilize antibiotics as self-medication. The derived reasons for SMA were convenience (63.3%) and cost-saving (34.8%). Tonsillitis was the most common ailment behind SMA (55.5%). Log-binominal regression revealed that non-insured and low level of education participants were more likely to predict SMA. Regarding the practice, 40% changed the dose and/or antibiotics mainly owing to improvement (53.7%) or worsening of the condition (37.9%). The most commonly used antibiotic was amoxicillin/clavulanic acid (32.5%). Conclusions: Two out of three individuals in Sudan practice SMA mainly to manage upper respiratory tract ailments. Thus, the necessity of implementing an antimicrobial stewardship program throughout the country, as well as implementing effective legislation to prohibit dispensing antibiotics without prescription is urgently required.

Breast cancer (BC) is one of the main types of cancer that endangers women’s lives. The characteristics of triple-negative breast cancer (TNBC) include a high rate of recurrence and the capacity for metastasis; therefore, new therapies are urgently needed to combat TNBC. Dual targeting HDAC6 and Hsp90 has shown good synergistic effects in treating metastatic TNBC. The goal of this study was to find potential HDAC6 and Hsp90 dual inhibitors. Therefore, several in silico approaches have been used. An e-pharmacophore model generation based on the HDAC6-ligand complex and subsequently a pharmacophore-based virtual screening on 270,450 natural compounds from the ZINC were performed, which resulted in 12,663 compounds that corresponded to the obtained pharmacophoric hypothesis. These compounds were docked into HDAC6 and Hsp90. This resulted in the identification of three compounds with good docking scores and favorable free binding energy against the two targets. The top three compounds, namely ZINC000096116556, ZINC000020761262, and ZINC000217668954, were further subjected to ADME prediction and molecular dynamic simulations, which showed promising results in terms of pharmacokinetic properties and stability. As a result, these three compounds can be considered potential HDAC6 and Hsp90 dual inhibitors and are recommended for experimental evaluation.

Based on the importance of multi drug resistant and biofilm forming bacterial spread, the current research work aimed on synthesizing the nanoparticles of zinc oxide from the plant parts of Limonia acidissima. They were assayed for their antibacterial activities against biofilm forming urinary tract infected pathogens including Salmonella paratyphi, Shigella, Streptococcus, Staphylococcus and Klebsiella pneumonia which was confirmed by anti-microbial susceptibility test, 24-well polystyrene plate and modified tube test methods. The formulation of nanoparticles was confirmed by UV–Visible spectrophotometry. Fourier transform infrared spectroscopy revealed the formation of biomolecules that has great involvement in stabilizing the zinc oxide. The size as well as the shape with high resolution was confirmed with electron microscopical studies. It is very clear that zinc oxide nanoparticles have great antimicrobial effect because of its inhibition role against tested urinary tract bacteria by various invitro experiments. This provides a positive thinking on novel drug discovery, in which human health can be improved. Hence, this study provides a scientific support to the medicinal uses of zinc oxide nanoparticles for the treatment of microbial infections.

Hepatitis is an inflammatory disease of the liver and is considered one of the leading causes of death worldwide. Due to its scavenging activity, Punica granatum may be used for the treatment and prevention of liver diseases. The current study investigated the protective mechanism underlying the effects of pomegranate against a rat model of carbon tetrachloride–induced liver injury. Intraperitoneal injection of CCl4 resulted in liver inflammation, oxidative stress, and accumulation of lipid in hepatocytes. CCl4 induced a downregulation of superoxide dismutase (SOD), glutathione (GSH), and melonaldehyde (MDA). Pomegranate protection was assessed in terms of biochemical parameters, histopathology, and immunohistochemistry. Promegranate administration decreased inflammation, elevated serum enzymes and ROS production, and countered the debilitating effects caused by CCl4. In addition, CCl4-induced histological changes were absent in the crude pomegranate extract group, which also enhanced the scavenging activity of reactive oxygen species by enhancing the antioxidant defense mechanism as confirmed by detecting MDA, SOD, and GSH expressions. The migration of CD68+ macrophages was halted at the injured area of the central vein and the number of macrophages was reduced to the normal control by the crude extract compared to the positive control silymarin group. Likewise, protective effects of ethylacetate and the aqueous fraction of the crude extract were also observed. However, the butanol and n-hexane fractions displayed increased levels of ALT, AST, and ALP as compared to silymarin. About 25% damage to hepatocytes was observed in the butanol and n-hexane group by histopathological examination, which is a little better compared to the CCl4-treated group. The crude extract and its ethyl acetate and aqueous fractions may be accountable for the hepatoprotective potential of Punica granatum, which was further confirmed by in vivo experiments. Together, these findings confirm that pomegranate exerts hepatoprotective activity against CCl4-induced oxidative stress and liver damage.

The present study was conducted to evaluate the acute toxicity and anti-inflammatory effect in vivo, as well as the antioxidant activity, of the essential oil of Thymus leptobotrys Murb. The results indicate that the tested essential oil is non-toxic, with an estimated LD50 of 2500 mg kg−1 of mice body weight. The anti-inflammatory test revealed that, at a dose of 200 mg kg−1, the essential oil reduced rat paw edemas by 89.59% within 3 h of oral administration, this reduction in edema size was greater than that obtained with indomethacin (75.78%). The antioxidant activity (IC50) of Thymus leptobotrys Murb essential oil was 346.896 µg mL−1 and 861.136 mg Trolox equivalent/g essential oil in the 2.2-diphenyl1-picryl-hydrazyl radical scavenging capacity (DPPH) and Trolox equivalent antioxidant capacity (TEAC) assays, respectively. The toxicity test reveals an LD50 greater than 2500 mg kg−1 of body weight of mice which classifies it within category 5 of non-toxic substances that can be administered orally. These results suggest that the essential oil of Thymus leptobotrys Murb is not toxic, and it represents a valuable source of anti-inflammatory and antioxidant metabolites.