Systematic exploration of Ziziphus species collection and gene identification influencing physiological traits using genotype-by-sequencing technology.

The Ziziphus genus, belonging to the Rhamnaceae family, holds significant economic, nutritional, and medicinal value. However, much remains to be discovered about its diversity and physical characteristics. Factors such as growth, resilience to changes, disease resistance, and unique features contribute to the quality of Ziziphus species. This study aims to investigate the genomes of 200 genotypes from five Ziziphus species: Ziziphus jujuba (Zj), Ziziphus nummularia (Zm), Ziziphus oxyphylla (Zx), Ziziphus mauritiana (Zm), and the cultivated variety Ziziphus jujube var. jujube, collected from Pakistan and China. Our goal is to identify single nucleotide polymorphisms (SNPs) associated with eight different traits and understand the genetic diversity within the selected Ziziphus species and their genotypes. Using high-quality SNPs obtained through genotype-by-sequencing (GBS), we conducted population structure, phylogenetic, and principal coordinates analyses, identifying a total of 10,945 clean SNPs. These genotypes were categorized into two groups, A and B. Natural Ziziphus variants in Pakistan, specifically Z. jujuba and Z. nummularia, exhibited high levels of genetic diversity and polymorphic information content (PIC) of 0.46 and 0.41, respectively, compared to other species. Furthermore, we identified 15 influential candidate genes that play crucial roles in regulating agronomic traits, such as fruit width and diameter, leaf width, plant height, and stem diameter within this group. This study provides valuable insights that can be utilized in Ziziphus breeding efforts.

In silico homology modeling of dengue virus non-structural 4B (NS4B) protein and its molecular docking studies using triterpenoids.

BACKGROUND: Dengue fever has become a significant worldwide health concern, because of its high morbidity rate and the potential for an increase in mortality rates due to lack of adequate treatment. There is an immediate need for the development of effective medication for dengue fever. METHODS: Homology modeling of dengue virus (DENV) non-structural 4B (NS4B) protein was performed by SWISS-MODEL to predict the 3D structure of the protein. Structure validation was conducted using PROSA, PROCHECK, Ramachandran plot, and VERIFY-3D. MOE software was used to find out the in-Silico inhibitory potential of the five triterpenoids against the DENV-NS4B protein. RESULTS: The SWISS-MODEL was employed to predict the three-dimensional protein structure of the NS4B protein. Through molecular docking, it was found that the chosen triterpenoid NS4B protein had a high binding affinity interaction. It was observed that the NS4B protein binding energy for 15-oxoursolic acid, betulinic acid, ursolic acid, lupeol, and 3-o-acetylursolic acid were - 7.18, - 7.02, - 5.71, - 6.67 and - 8.00 kcal/mol, respectively. CONCLUSIONS: NS4B protein could be a promising target which showed good interaction with tested triterpenoids which can be developed as a potential antiviral drug for controlling dengue virus pathogenesis by inhibiting viral replication. However, further investigations are necessary to validate and confirm their efficacy.

Co-application of Parthenium biochar and urea effectively mitigate cadmium toxicity during wheat growth.

Environmental contamination by cadmium (Cd), a highly toxic heavy metal, poses significant health risks to plants and humans. Biochar has been effectively used to promote plant growth and productivity under Cd stress. This study presents an innovative application of biochar derived from the invasive weed Parthenium hysterophorus to promote plant growth and productivity under Cd stress. Our study includes detailed soil and plant analyses, providing a holistic perspective on how biochar and urea amendments influence soil properties, nutrient availability, and plant physiological responses. To address these, we established seven treatments: the control, Cd alone (5 mg kg-1), biochar alone (5 %), urea alone (3 g kg-1), biochar with Cd, urea with Cd, and a combination of biochar and urea with Cd. Cd stress alone significantly reduced plant growth indicators such as shoot and root length, fresh and dry biomass, chlorophyll content, and grain yield. However, the supplementation of biochar, urea, or their combination significantly increased shoot length (by 48%, 34%, and 65%), root length (by 73%, 46%, and 70%), and fresh shoot biomass (by 4%, 31%, and 4%), respectively. This improvement is attributed to enhanced soil properties and improved nutrient absorption. The biochar-urea combination also enhanced Cd tolerance by improving total chlorophyll content by 14 %, 13 %, and 16 % compared to the control, respectively. Similaly, these treatments significantly (p < 0.05) boosted the activity of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase by 51 %, 30 %, and 51 %, respectively, thereby mitigating oxidative stress as a defensive mechanism. The Cd tolerance was improved by biochar, urea, and their combinations, which reduced Cd content in the shoots (by 60.5 %, 38.9 %, and 51.3 %), roots (by 47.5 %, 23.9 %, and 57.6 %), and grains (by 58.1 %, 30.2 %, and 38.3 %) relative to Cd stress alone, respectively. The synergistic effects of biochar and urea are achieved through improved soil properties, nutrient availability, activating antioxidant defense mechanisms, and minimizing the accumulation of metal ions in plant tissues, thereby enhancing plant defenses against Cd stress. Conclusively, converting invasive Parthenium weed into biochar and combining it with urea offers an environmentally friendly solution to manage its spreading while effectively mitigating Cd stress in crops.

Phytochemical Diversity and Biological Effects of Juniperus thurifera L., Essential Oil : A Comparative Study using In Vitro and In Silico Methods.

This study aims to elucidate the phytochemical diversity and biological activities of J. thurifera essential oil (JTEO) through a comparative analysis of samples from two distinct regions: Tensift-Al Haouz and Azilal, using both in vitro and in silico methods. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed 21 components in the Tensift-Al Haouz JTEO (99.99% of the oil) and 23 components in the Azilal JTEO (99.58% of the oil), with oxygenated monoterpenes being the predominant compounds in both. The biological activities were assessed in vitro. Antioxidant properties, evaluated using DPPH, FRAP, and ABTS assays, showed significant activity in both oils. Antibacterial activity was tested against two strains of Gram-positive and two strains of Gram-negative bacteria, with both oils demonstrating notable bacterial growth inhibition. Enzymatic assays assessed the antidiabetic (α-amylase and α-glucosidase), dermo-protective (tyrosinase and elastase), and neuroprotective (AChE and BChE) activities. Both oils displayed substantial inhibitory effects across all tested activities, with variations attributed to their distinct chemical compositions. In silico analyses of six target enzymes confirmed significant binding affinities of the major compounds. Notably, 2,2'-Thiobis(6-tert-butyl-p-cresol) exhibited strong binding affinities with AChE, BChE, α-amylase, α-glucosidase, tyrosinase, and elastase, with binding energies ranging from -10.0 to -6.2 kcal/mol.

Biological Properties of Mentha viridis L. Essential Oil and Its Main Monoterpene Constituents.

This research aimed to evaluate the antidiabetic, dermatoprotective, and antibacterial activities of Mentha viridis L. essential oil (MVEO) collected in the province of Ouezzane (Northwest Morocco). Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the main constituents of MVEO were carvone (37.26 %), 1,8-cineole (11.82 %), limonene (5.27 %), α-terpineol (4.16 %), and ß-caryophyllene (4.04 %). MVEO showed strong inhibitory effects on α-amylase and α-glucosidase activities, exceeding those of acarbose, but weak anti-elastase activity. The main compounds, ß-caryophyllene (IC50=79.91±2.24 and 62.08±2.78 µg/mL) and limonene (IC50=90.73±3.47 and 68.98±1, 60 µg/mL), demonstrated the strongest inhibitory effects on both digestive enzymes (α-glucosidase and α-amylase, respectively). In silico investigations, using molecular docking, also showed the inhibitory potential of these bioactive compounds against the enzymes tested. In conclusion, MVEO, due to its main components such as limonene, 1,8-cineole, ß-caryophyllene, carvone, and α-terpineol, shows promising prospects for drug discovery and natural therapeutic applications.

Degradation of Argan oils used in edible and cosmetic applications after exposure to UV light.

This study investigates for the first time the effects of UV light exposure on the chemical composition of artisanal and cold-pressed culinary and cosmetic argan oils, as well as their quality and biological activities. We ascertained the oxidative stability of both types of oil through measurements of the peroxide value, acidity, UV-spectrophotometric indexes (E232 and E270), and iodine value. Over the course of eight hours at room temperature, the impact of UV light on the breakdown of tocopherols, polyphenols, chlorophylls, and carotenoid pigments was examined. The findings showed that during photo-oxidation, acidity, peroxide value, and particular extinction coefficients (E232 and E270) gradually increased. On the other hand, a decline in the content of polyphenols, tocopherols, carotenoid, and chlorophyll was noted. Interestingly, iodine levels failed to improve. Although after an eight-hour degradation, the physicochemical profile of argan oils remained exceptional. DPPH• (1,1-Diphenyl-2-picrylhydrazyl) antioxidant activity tests showed a gradual decrease in radical inhibition over time, which was attributed to lower levels of tocopherol and polyphenol. However, roasted oils showed antifungal action against Botrytis cinerea fungus, while Argan vegetable oils showed no activity against Escherichia coli, Microbacterium resistens, Staphylococcus saprophyticus, and Raoultella ornithinolytica, according to antimicrobial assays.

Phytochemical-mediated regulation of aflatoxigenic fungi contamination in a shifting climate and environment.

Mycotoxin contamination poses a significant problem in developing countries, particularly in northern Pakistan's fluctuating climate. This study aimed to assess aflatoxin contamination in medicinal and condiment plants in Upper Dir (dry-temperate) and Upper Swat (moist-temperate) districts. Plant samples were collected and screened for mycotoxins (Aflatoxin-B1 and Aflatoxin-B-2). Results showed high levels of AFB-1 (11,505.42 ± 188.82) as compared to AFB-2 (846 ± 241.56). The maximum contamination of AFB-1 in Coriandrum sativum (1154.5 ± 13.43 ng to 3328 ± 9.9 ng) followed by F. vulgare (883 ± 9.89 ng to 2483 ± 8.4 ng), T. ammi (815 ± 11.31 ng to 2316 ± 7.1 ng), and C. longa (935.5 ± 2.12 ng to 2009 ± 4.2 ng) while the minimum was reported in C. cyminum (671 ± 9.91 ng to 1995 ± 5.7 ng). Antifungal tests indicated potential resistance in certain plant species (C. cyminum) while A. flavus as the most toxins contributing species due to high resistance below 80% (54.2 ± 0.55 to 79.5 ± 2.02). HPLC analysis revealed hydroxyl benzoic acid (5136 amu) as the dominant average phytochemical followed by phloroglucinol (4144.31 amu) with individual contribution of 8542.08 amu and 12,181.5 amu from C. cyaminum. The comparison of average phytochemicals revealed the maximum concentration in C. cyminum (2885.95) followed by C. longa (1892.73). The findings revealed a statistically significant and robust negative correlation (y = - 2.7239 × + 5141.9; r = - 0.8136; p < 0.05) between average mycotoxins and phytochemical concentrations. Temperature positively correlated with aflatoxin levels (p < 0.01), while humidity had a weaker correlation. Elevation showed a negative correlation (p < 0.05), while geographical factors (latitude and longitude) had mixed correlations (p < 0.05). Specific regions exhibited increasing aflatoxin trends due to climatic and geographic factors.

Methyl-CpG-Binding Protein 2 Emerges as a Central Player in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.

MECP2 and its product methyl-CpG binding protein 2 (MeCP2) are associated with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), which are inflammatory, autoimmune, and demyelinating disorders of the central nervous system (CNS). However, the mechanisms and pathways regulated by MeCP2 in immune activation in favor of MS and NMOSD are not fully understood. We summarize findings that use the binding properties of MeCP2 to identify its targets, particularly the genes recognized by MeCP2 and associated with several neurological disorders. MeCP2 regulates gene expression in neurons, immune cells and during development by modulating various mechanisms and pathways. Dysregulation of the MeCP2 signaling pathway has been associated with several disorders, including neurological and autoimmune diseases. A thorough understanding of the molecular mechanisms underlying MeCP2 function can provide new therapeutic strategies for these conditions. The nervous system is the primary system affected in MeCP2-associated disorders, and other systems may also contribute to MeCP2 action through its target genes. MeCP2 signaling pathways provide promise as potential therapeutic targets in progressive MS and NMOSD. MeCP2 not only increases susceptibility and induces anti-inflammatory responses in immune sites but also leads to a chronic increase in pro-inflammatory cytokines gene expression (IFN-γ, TNF-α, and IL-1ß) and downregulates the genes involved in immune regulation (IL-10, FoxP3, and CX3CR1). MeCP2 may modulate similar mechanisms in different pathologies and suggest that treatments for MS and NMOSD disorders may be effective in treating related disorders. MeCP2 regulates gene expression in MS and NMOSD. However, dysregulation of the MeCP2 signaling pathway is implicated in these disorders. MeCP2 plays a role as a therapeutic target for MS and NMOSD and provides pathways and mechanisms that are modulated by MeCP2 in the regulation of gene expression.

Microsatellite-based diversity analysis and the development of core-set germplasm in Pakistani barley lines.

Illustrating the population structure and genetic diversity in selected germplasm resources (after three year multi locations trials) plays a key role which directly utilize the selection of lines in a population for accumulative trait breeding in crops. In order to further understand, the structure of population and genetic variability, we explored 100 selected lines, cultivated for three consecutive years (2016-2019) in swat, University of Malakand, Khyber Pakhtunkhwa Pakistan and Provinces of China (Chongqing and Beijing) with 33 mapped SSR markers. The integrated population structure analysis in a core of hundred germplasm with Pakistani origin with three approved commercial barley cultivars have strong stratification that allowed their division into four major subpopulations (i.e. PI, PII, PIII and PIV) and an admixture subpopulation, with 52, 9, 15 and 27 germplasm respectively. A total of 133 alleles were identified with mean value of 0.80 Polymorphic information content. The number of alleles detected by the system varied from two alleles amplified to as six with an average of 4.03 per SSR marker pair. The gene diversity ranged from 0.56 to 0.98 with an average of 0.82 in selected germplasm resources. Based on the SSR data, the 100 selected germplasm with three cultivars were classified into four main phylogenetic Linages (LI, LII, LIII and LIV) which corresponded to the phylogenic grouping in genotypes. We assembled a core set of 20 barley genotypes (~1/5 of original population size) to sustain sufficient mapping of SSR marker with Phenotype, in which we proposed four SSR markers, Bmac0040, Bmac0134, Bmag0125 and Bmag0211 for malt gene and marker (Bmac0399) for tolerance to salinity gene, which will be applicable for marker assisted breeding in barley gene resources.

Identification of the Seaweed Metabolites as Potential Anti-tubercular Agents Against Human Pantothenate synthetase: An In Silico Approach.

Tuberculosis is the disease which is caused due to the contagion of Mycobacterium tuberculosis. The multidrug resistance Mycobacterium tuberculosis is the main hassle in the treatment of this worldwide health threats. Pantothenate synthase is a legitimate goal for rational drug designing against Mycobacterium tuberculosis. The enzyme is most active in the presence of magnesium or manganese. Marine algal cell wall is rich in sulfated polysaccharides such as fucoidans (brown algae), κ-carrageenans (red algae), and ulvan (green algae) with various favorable biological activities such as anticoagulant, antiviral, antioxidative, anticancer, and immunomodulating activities. In this study, we have modeled binding modes of selected known anti-tubercular compounds and different solvent extract against pantothenate synthase using advanced docking program AutoDock 4.2 tool. In our current study, in silico experiments were carried out to determine if fucoidan, κ-carrageenan, and ulvan sulfated polysaccharides could be a potential target against PANc (pantothenate synthetase), with the goal of identifying potential inhibitors as anti-TB leads targeting PANc for further wet lab validation. Two bioactive compounds were docked to the Mtb pantothenate synthetase protein binding site, with docking scores ranging from - 5.57 to - 2.73. κ-carrageenan had the best pose and docking score, with a Ligand fit score of - 5.815. Ulvan did not dock with the protein. The molecular dynamics simulations were conducted with substrate and ligand bounded fucoidan and κ-carrageenan for 150 ns and the protein Mtb pantothenate synthetase showed a stable conformation in the simulation, with tight amino acid contributions binding to the ligand molecule. RMSD characterizes the conformation and stability of protein ligand complexes, with higher fluctuations indicating low stability and minimal low-level fluctuations indicating equilibration and stability. The graph for RMSF shows significant peaks due to fluctuations in active site regions and other peaks indicating the adaptation of the ligand molecule to the protein binding pocket. From the molecular dynamics study, it is clear that the compounds are having good binding affinity in the active site. The root mean square deviation, root mean square fluctuations, and radius of gyration are supportive evidences which helped us to conclude that the compounds κ-carrageenan and fucoidan are suitable lead molecules for inhibiting pantothenate synthetase. Based on these evidences, the natural compounds from seaweeds can be tested clinically either alone or in combinations against the protein, which could facilitate the designing or the synthesis of new lead molecules as drugs against the tuberculosis.

Synthesis and Characterization of MIPs for Selective Removal of Textile Dye Acid Black-234 from Wastewater Sample.

Herein, a molecularly imprinted polymer (MIP) was prepared using bulk polymerization and applied to wastewater to aid the adsorption of targeted template molecules using ethylene glycol dimethacrylate (EGDMA), methacrylic acid (MAA), acid black-234 (AB-234), 2,2'-azobisisobutyronitrile (AIBN), and methanol as a cross linker, functional monomer, template, initiator, and porogenic solvent, respectively. For a non-molecularly imprinted polymer (NIP), the same procedure was followed but without adding a template. Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a surface area analyzer were used to determine the surface functional groups, morphology and specific surface area of the MIP and NIP. At pH 5, the AB-234 adsorption capability of the MIP was higher (94%) than the NIP (31%). The adsorption isotherm data of the MIP correlated very well with the Langmuir adsorption model with Qm 82, 83 and 100 mg/g at 283 K, 298 K, and 313 K, respectively. The adsorption process followed pseudo-second-order kinetics. The imprinted factor (IF) and Kd value of the MIP were 5.13 and 0.53, respectively. Thermodynamic studies show that AB-234 dye adsorption on the MIP and NIP was spontaneous and endothermic. The MIP proved to be the best selective adsorbent for AB-234, even in the presence of dyes with similar and different structures than the NIP.

A Comprehensive Mechanistic Antibacterial and Antibiofilm Study of Potential Bioactive ((BpA)2bp)Cu/Zn Complexes via Bactericidal Mechanisms against Escherichia coli.

Bacterial resistance to antibiotics and host defense systems is primarily due to bacterial biofilm formation in antibiotic therapy. In the present study, two complexes, bis (biphenyl acetate) bipyridine Cu (II) (1) and bis (biphenyl acetate) bipyridine Zn (II) (2), were tested for their ability to prevent biofilm formation. The minimum inhibitory concentration and minimum bactericidal concentration of complexes 1 and 2 were 46.87 ± 1.822 and 93.75 ± 1.345 and 47.87 ± 1.345 and 94.85 ± 1.466 µg/mL, respectively. The significant activity of both complexes was attributed to the damage caused at the membrane level and was confirmed using an imaging technique. The biofilm inhibitory potential levels of complexes 1 and 2 were 95% and 71%, respectively, while the biofilm eradication potential levels were 95% and 35%, respectively, for both complexes. Both the complexes showed good interactions with the E. coli DNA. Thus, complexes 1 and 2 are good antibiofilm agents that exert their bactericidal actions possibly by disrupting the bacterial membrane and interacting with the bacterial DNA, which can act as a powerful agent to restrain the development of bacterial biofilm on therapeutic implants.

Co-Doped CeO2/Activated C Nanocomposite Functionalized with Ionic Liquid for Colorimetric Biosensing of H2O2 via Peroxidase Mimicking.

Hydrogen peroxide acts as a byproduct of oxidative metabolism, and oxidative stress caused by its excess amount, causes different types of cancer. Thus, fast and cost-friendly analytical methods need to be developed for H2O2. Ionic liquid (IL)-coated cobalt (Co)-doped cerium oxide (CeO2)/activated carbon (C) nanocomposite has been used to assess the peroxidase-like activity for the colorimetric detection of H2O2. Both activated C and IL have a synergistic effect on the electrical conductivity of the nanocomposites to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The Co-doped CeO2/activated C nanocomposite has been synthesized by the co-precipitation method and characterized by UV-Vis spectrophotometry, FTIR, SEM, EDX, Raman spectroscopy, and XRD. The prepared nanocomposite was functionalized with IL to avoid agglomeration. H2O2 concentration, incubation time, pH, TMB concentration, and quantity of the capped nanocomposite were tuned. The proposed sensing probe gave a limit of detection of 1.3 × 10-8 M, a limit of quantification of 1.4 × 10-8 M, and an R2 of 0.999. The sensor gave a colorimetric response within 2 min at pH 6 at room temperature. The co-existing species did not show any interference during the sensing probe. The proposed sensor showed high sensitivity and selectivity and was used to detect H2O2 in cancer patients' urine samples.

Rapid Detection of Cd2+ Ions in the Aqueous Medium Using a Highly Sensitive and Selective Turn-On Fluorescent Chemosensor.

Herein, a novel optical chemosensor, (CM1 = 2, 6-di((E)-benzylidene)-4-methylcyclohexan-1-one), was designed/synthesized and characterized by 1H-NMR and FT-IR spectroscopy. The experimental observations indicated that CM1 is an efficient and selective chemosensor towards Cd2+, even in the presence of other metal ions, such as Mn2+, Cu2+, Co2+, Ce3+, K+, Hg2+,, and Zn2+ in the aqueous medium. The newly synthesized chemosensor, CM1, showed a significant change in the fluorescence emission spectrum upon coordination with Cd2+. The formation of the Cd2+ complex with CM1 was confirmed from the fluorometric response. The 1:2 combination of Cd2+ with CM1 was found optimum for the desired optical properties, which was confirmed through fluorescent titration, Job's plot, and DFT calculation. Moreover, CM1 showed high sensitivity towards Cd2+ with a very low detection limit (19.25 nM). Additionally, the CM1 was recovered and recycled by the addition of EDTA solution that combines with Cd2+ ion and, hence, frees up the chemosensor.

One Pot Synthesis, Biological Efficacy of AuNPs and Au-Amoxicillin Conjugates Functionalized with Crude Flavonoids Extract of Micromeria biflora.

Amoxicillin is the most widely used antibiotic in human medicine for treating bacterial infections. However, in the present research, Micromeria biflora's flavonoids extract mediated gold nanoparticles (AuNPs) were conjugated with amoxicillin (Au-amoxi) to study their efficacy against the inflammation and pain caused by bacterial infections. The formation of AuNPs and Au-amoxi conjugates were confirmed by UV-visible surface plasmon peaks at 535 nm and 545 nm, respectively. The scanning electron microscopy (SEM), zeta potential (ZP), and X-ray diffraction (XRD) studies reveal that the size of AuNPs and Au-amoxi are found to be 42 nm and 45 nm, respectively. Fourier-transform infrared spectroscopy (FT-IR) absorption bands at 3200 cm-1, 1000 cm-1, 1500 cm-1, and 1650 cm-1 reveal the possible involvement of different moieties for the formation of AuNPs and Au-amoxi. The pH studies show that AuNPs and Au-amoxi conjugates are stable at lower pH. The carrageenan-induced paw edema test, writhing test, and hot plate test were used to conduct in vivo anti-inflammatory and antinociceptive studies, respectively. According to in vivo anti-inflammatory activity, Au-amoxi compounds have higher efficiency (70%) after 3 h at a dose of 10 mg/kg body weight as compared to standard diclofenac (60%) at 20 mg/kg, amoxicillin (30%) at 100 mg/kg, and flavonoids extract (35%) at 100 mg/kg. Similarly, for antinociceptive activities, writhing test results show that Au-amoxi conjugates produced the same number of writhes (15) but at a lower dose (10 mg/kg) compared to standard diclofenac (20 mg/kg). The hot plate test results demonstrate that the Au-amoxi has a better latency time of 25 s at 10 mg/kg dose when compared to standard Tramadol of 22 s at 30 mg/ kg, amoxicillin of 14 s at 100 mg/kg, and extract of 14 s at 100 mg/kg after placing the mice on the hot plate for 30, 60, and 90 min with a significance of (p ≤ 0.001). These findings show that the conjugation of AuNPs with amoxicillin to form Au-amoxi can boost its anti-inflammatory and antinociceptive potential caused by bacterial infections.

Cardioprotective study of Eriobotrya japonica leaf extracts against carbon tetrachloride induced toxicity in rats.

The Rosaceae family includes the evergreen subtropical tree known as Eriobotrya japonica Lindl (loquat). To test the effect of several E. japonica leaf extracts on shielding the heart from carbon tetrachloride (CCl4) cytotoxic effects, we employed carbon tetrachloride (CCl4), a highly toxic chemical, to cause cardiotoxicity in rats. The heart function enzymes that were examined were lactate dehydrogenase (LDH) and Creatine Kinase. When compared to both the hazardous and normal groups, it was discovered that the protective dose of ethyl acetate extract (200 mg/Kg) and aqueous extract (100 and 200 mg/Kg) lowered the cardiac indicators. Total protein, malondialdehyde (MDA), and non-protein sulfhydryls (NP-SH) indicators were used to assess myocardial oxidative stress. Rats pretreated with ethyl acetate (200 mg/Kg) and aqueous extract (100 and 200 mg/Kg) showed higher levels of total protein than the control group. When compared to the silymarin group, all of the loquat leaf extracts examined in this study increased the amount of the MDA enzyme. The data also demonstrated that, when compared to the results from the normal group, aqueous extract (100 and 200 mg/Kg) enhanced the amount of NP-SH. The histopathology showed that administration of all loquat leaf extracts at doses of (100 mg/kg, 200 mg/kg) before CCl4 intoxication greatly reduced the modifications that were exhibited by CCl4 and preserved cardiac muscles that were very equivalent to those of normal control. Based on the aforementioned data, we deduced that loquat leaf aqueous extract provided the highest protection for heart tissue against the effects of CCl4 intoxication. Through chemical examination of the methanolic extract, four flavonoids were extracted and identified. Their structures were found to be kaempferol-3-O-rhamnoside 1, quercetin-3-O-rhamnoside 2, quercetin-3,7 di-O-glycerides 3, and roseoside 4.

Evidence of drug-induced hepatotoxicity in the Maghrebian population.

Drug-induced hepatotoxicity is one of the most challenging hepatic diseases faced nowadays due to a large number of drugs currently used in clinical practice, the enormous dietary supplements which are potentially hepatotoxic, as well as the ability to appear with different clinical symptoms and the absence of specific markers. The current research survey was conducted to investigate drug-induced hepatotoxicity and demographic characteristics of patients with liver damage in the general Maghrebian population between 1992 and 2018. To achieve this goal a questionnaire was adopted to report details on the undesirable effects of drugs and demographic characteristics of affected patients. The results obtained in the current survey showed that 1001 in 25 093 cases of drug-induced toxicity were registered with drug-induced liver damage between 1992 and 2018. Regarding demographic characteristics of affected patients, the most affected age group was 18 to 44-years-old with a percentage of 45.70% followed by the age group 45 to 64-year-old with a percentage of 27.20%. Females were the most frequently affected by the hepatic side effects of drugs vs. males. Paracetamol, isoniazid, rifampicin, and pyrazinamide were the main responsible drugs for liver damage in the study population. Alteration of biological parameters and subclinical phenomena were used as clinical manifestations of liver damage in the study population. The outcome of the present study suggests paying more attention to drugs used for medication and the involvement of rigorous clinical monitoring to prevent or to minimize the side effects of drugs.

Nephroprotective effect of persimmon leaves (Diospyros kaki L.f.) against CCl4-induced renal toxicity in Swiss Albino rats.

Diospyros kaki L.f. fruit and leaves are traditionally used for the treatment of hypertension, angina, internal hemorrhage, antithrombotic and anti-inflammatory effects.In the current study, the protective effects of ethyl acetate (Per-1), n-butanol (Per-2), and aqueous (Per-3) fractions of Diospyros kaki leaves against carbon tetrachloride (CCl4) induced nephrotoxicity in Swiss albino rats were tested. Animal were divided into nine groups; each group consists of six animals. The groups were : group I was untreated and kept as control, group II was treated with CCl4 only, group III (silymarin with CCl4); group IV (Per-1 100 mg/kg with CCl4);group V (Per-1 200 mg/kg with CCl4); group VI (Per-2 100 mg/kg with CCl4); group VII (Per-2 200 mg/kg with CCl4); group VIII (Per-3 100 mg/kg with CCl4); and group IX (Per-3 200 mg/kg with CCl4). Silymarin was used as standard drug. All tested fractions were found active (except Per-1 at low dose of 100 mg/kg) with significant value (p < 0.001) compared to CCl4 only group. Serum creatinine, malondialdehyde (MDA), and uric acid were significantly (p < 0.001) lowered in group VII-IX as compared to CCl4 only group. Similarly, total protein (TP) and non-protein sulfhydryls(NP-SH) level in kidney tissues were significantly (p < 0.001) elevated in the same groups compared to CCl4 only group. Further to check the cardio-protective potential, biochemical parameters such as LDH, creatine kinase, TP, MDA, and NP-SH levels in myocardial tissues were also estimated.These findings confirmed that the n-butanol and aqueous fractions are active and recommended for further bioactive phytoconstituents screening. Repeated column chromatography on silica gel G and sephadex-LH-20 of the active n-butanol fraction, four flavonoids were isolated. Based on the spectroscopic NMR data, compounds were identified as kaempferol (1), quercetin (2), astragalin (3), and rutin (4).

Synthesis and Characterization of Novel Hydrazone Derivatives of Isonicotinic Hydrazide and Their Evaluation for Antibacterial and Cytotoxic Potential.

Hydrazones are active compounds having an azomethine -NHN=CH group and are widely studied owing to their ease of preparation and diverse pharmacological benefits. Novel isonicotinic hydrazone derivatives of vanillin aldehyde and salicyl aldehyde were synthesized that had azomethine linkages and were characterized by UV-Visible, FTIR, EI-MS, 1H-NMR and 13C-NMR spectroscopy. The compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus subtilus, and Escherichia coli using disc diffusion and minimum inhibitory concentration (MIC) methods. For cytotoxicity, a brine shrimp lethality test was performed to calculate the lethal concentration (LC50). The results demonstrated appreciable antibacterial activities against the applied strains, amongst which the compounds coded NH3 and NH5 showed maximum inhibition and MIC responses. In terms of cytotoxic activity, the maximum effect was observed in compound NH5 and NH6 treatments with minimum survival percentages of 36.10 ± 3.45 and 32.44 ± 2.0, respectively. These hydrazones could be potential candidates in antitumorigenic therapy against various human cancer cells.

Synthesis of Copper Oxide-Based Nanoformulations of Etoricoxib and Montelukast and Their Evaluation through Analgesic, Anti-Inflammatory, Anti-Pyretic, and Acute Toxicity Activities.

Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.