Search

Solubility enhancement of poorly aqueous-soluble drugs, like Terbinafine (TBN), is a critical challenge in formulating effective dosage forms. This study focused on developing β-cyclodextrin (β-CD) and polyacrylamide (PAM)-based microgels to address the solubility issue of TBN, classified as a biopharmaceutics classification system class II drug. The microgels were crafted through free radical polymerization, employing methylene bisacylamide as a cross-linker and methacrylic acid as a monomer, initiated by ammonium persulfate. Comprehensive characterizations, including Fourier transform infrared, thermo-gravimetric analysis, differential scanning calorimetry, scanning electron microscopy, powder X-ray diffractometry analysis, Zeta size, and Zeta potential, were conducted. In vitro studies, such as drug release and swelling, were performed at pH 1.2. Toxicity analysis in rabbits revealed zero toxicity. These β-CD/PAM microgels successfully enhanced the solubility of TBN.

Citronellol (CT) is a monoterpene alcohol present in the essential oil of plants of the genus Cymbopogon and exhibits diverse pharmacological activities. The aim of the current study was to investigate the hepatoprotective potential of CT against ethanol-induced toxicity in HepG2 cell lines. Silymarin (SIL) was used as a standard drug. MTT, crystal violet assay, DAPI, and PI staining were carried out to assess the effect of ethanol and CT on cell viability. RT-PCR determined the molecular mechanisms of hepatoprotective action of CT. CT ameliorated cell viability and restricted ethanol-induced cell death. DAPI and PI staining showed distinct differences in cell number and morphology. Less cell viability was observed in the diseased group obviously from strong PI staining when compared to the CT- and SIL-treated group. Moreover, CT showed downregulation of interleukin (IL-6), transforming growth factor-beta 1 (TGF-β1), collagen type 1 A 1 (COL1A1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and glutathione peroxidase-7 (GPX-7) levels. Molecular docking studies supported the biochemical findings. It is concluded that the cytoprotective activity of CT against ethanol-induced toxicity might be explained by its anti-inflammatory, immunomodulatory, and collagen-regulating effects.

The purpose of the current study is to assess the chemical profile, antioxidant, antimicrobial, and insecticide efficacy of essential oil derived from the leaf of Moroccan Mentha aquatica L. (MA-EO) using in vitro and in silico analysis. Using GC-MS/MS analysis, 18 components of MA-EO were identified, including linalool (42.42%), α-elemol (10.45%), α-terpineol (8.07%), linalyl acetate (7.37%), and caryophyllene (4.05%). Additionally, MA-EO has a strong antioxidant capacity with IC50 values of 0.64 ± 0.01 µg/mL using the DPPH assay and 0.167 ± 0.13 µg/mL using the ABTS test. Total antioxidant capacity activities were found to be 188.21 ± 0.31 mg EAA/g, while RP activities were 1.95 ± 0.023. The powerful antibacterial properties of MA-EO were proven to be effective against Escherichia coli and Candida albicans. MA-EO showed insecticidal potential using the fumigation experiment, with an LC50 of 3.33 μL/L in the air after 24 h of exposure. At a dose of 20 µL/mL, MA-EO reduced fertility, fecundity, and emergence of adult C. maculatus. MA-EO had 95% mortality at the same dosage. In silico analysis revealed that the antioxidant activity of MA-EO is linked to γ-eudesmol, while its antibacterial efficacy is associated with phenol, 2,4-di-tert-butyl-, and its antifungal capacity with phenol, 2,4-di-tert-butyl-. MA-EO demonstrates potent bactericidal, fungicidal, and bioinsecticide properties, making it effective for controlling bacteria, fungi, and insect pests in stored grains.

Breast cancer is the biggest cause of death among women worldwide. Natural chemicals from medicinal plants offer promise for cancer therapy. This research screens 29 Dryopteris species plant-derived chemicals, mostly phloroglucinols, for breast cancer therapy potential. First, we used Gaussian09 and DFT/B3LYP/6-311+G(d, p) calculations to evaluate compound stability and reactivity. We conducted molecular docking experiments to identify drugs with high binding affinity for the PI3Kα protein’s active pocket. DJ1–DJ22 were found to be the most effective PI3Kα inhibitors, with energies ranging from −8.0 to −9.2 kJ/mol. From in silico pharmacokinetic and bioactivity screening, DJ3, DJ7, and DJ18 were identified as promising PI3Kα inhibitors. PI3Kα backbone stability was tested in a water model using molecular dynamics simulations employing DJ3, DJ7, DJ18, and Trastuzumab as a pharmacological reference. Synthesis of target-hit DJ3, DJ7, and DJ18 derivatives may lead to breast cancer drug-like molecules for related cancers. The work uses in silico methods to find natural phloroglucinols for breast cancer therapy, enabling new chemotherapeutic drugs.

Acute myeloid leukemia (AML) takes center stage as a highly prevalent and aggressive clonal disorder affecting hematological stem cells. FMS-like tyrosine kinase 3 (FLT3) mutations were prevalent in nearly 30% of the AML cases. However, efforts have led to the development of anti-mutant FLT3 drugs, such as midostaurin, gilteritinib, and quizartinib, to improve treatments. Currently, we are exploring the ability of compounds from anti-leukemic plants to be used in AML therapies, focusing on mutant FLT3 inhibition. Employing computational techniques such as drug-likeness assessment, molecular docking, pharmacokinetics properties profiling, molecular dynamics simulations (MDS), and free energy calculations, we identified 43 out of 57 compounds with oral drug potential. Notably, 7 out of 43 compounds, including flavopiridol, sanggenol Q, norwogonin, oblongixanthones A, oblongixanthones B, apigenin, and luteolin exhibited strong binding affinities ranging from −9.0 to −9.8 kcal/mol, surpassing the control drug gilteritinib (−6.3 kcal/mol). Notably, flavopiridol and norwogonin displayed highly favorable pharmacokinetics and low toxicity profiles. MDS confirmed the stability of their binding through parameters such as root mean square deviation, root mean square fluctuation, and radius of gyration (R g) over 100 ns simulations. Flavopiridol and norwogonin emerge as promising candidates for the development of mutant FLT3 inhibitors. Therefore, experimental studies are warranted to validate their therapeutic potential.

Vetiveria zizanioides, known as vetiver grass, is renowned for its ecological significance in soil erosion control and the restoration of lands polluted by heavy metals. Additionally, this plant is extensively harvested for vetiver oil, widely utilized in both medicine and perfumery. The study was designed to investigate the phytochemicals, antilipase, hemoglobin antiglycation, antihyperglycemic, antifungal, and antibacterial properties of V. zizanioides. The GC-MS analysis revealed the presence of various volatile compounds, among which the most predominant ones, which are, 4,6,6-Trimethyl-2-(3-methylbuta-1,3-dienyl) −3-oxatricyclo [5.1.0.0(2,4)] octane, Cycloisolongifolene (8,9-dehydro-), and 9 H-Cycloisolongifolene (8-oxo-). It is noteworthy that this essential oil has shown significant inhibitory activity against α-amylase, α-glucosidase, pancreatic lipase, and glycation, with respective IC50 values of 0.47 ± 0.01, 0.42 ± 0.004, 0.58 ± 0.008, and 0.49 ± 0.005 mg/mL. Additionally, the antimicrobial activity of EoVZ was assessed against a diverse spectrum of Gram+ and Gram- bacteria, as well as fungi, using both disc-diffusion and broth-microdilution techniques. The results showed significant antimicrobial effects against all tested microorganisms, with inhibition zones ranging from 28.33 ± 1.66 mm to 9.0 ± 0.0 mm for bacteria and from 22.5 ± 1.7 mm to 14.0 ± 0.3 mm for fungi. Moreover, minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), and minimum fungicidal concentrations (MFC) were determined, with values ranging from 0.0625% to 2.0% (v/v) for bacteria and from 2.0% to 8.0% (v/v) for fungi. The MBC/MIC and MFC/MIC ratios indicated bactericidal and fungicidal mechanisms. This study underscores the prominent attributes of EoVZ, particularly its antimicrobial and antidiabetic properties, suggesting its potential as a natural and effective agent ensuring high safety standards for public health. [ABSTRACT FROM AUTHOR]

Opuntia ficus-indica, also known as the prickly pear, is a cactus belonging to the Cactaceae family. For centuries, this remarkable plant has been valued for its medicinal, environmental, and culinary uses. The primary objective of this research is to examine and contrast the chemical composition, functional attributes, and nutritional significance of Opuntia ficus-indica cladodes sourced from three distinct regions in Morocco: Oulad Boubker, Imzouren, and Skoura. According to the results, moisture content differs significantly between the three sites, from 88.21 ± 0.20% to 92.11 ± 0.10%, with an acid pH value. While the ash content remained consistent across all three samples. Carbohydrate content ranging from 55.40 ± 0.08% to 55.90 ± 0.60%, fat content from 2.30 ± 0.21 to 2.62 ± 0.09, protein from 7.54 ± 0.03% to 9.07 ± 0.16%, crude fibers from 20.52 ± 1.87% to 21.00 ± 0.20%, and soluble fibers from 15.08 ± 0.16% to 16.33 ± 1.25%. Additionally, total chlorophyll content varied between 102.64 ± 8.93 and 144.80 ± 3.08 mg.100 g−1 DM. The functional properties showed considerable differences between the three samples: the water holding capacity ranged from 109.58 ± 0.11 to 174.95 ± 0.06 g water.100 g−1 DM, the oil holding capacity from 129.27 ± 0.39 to 146.51 ± 0.39 g oil.100 g−1 DM and the solubility index from 25.75 ± 0.60 to 33.18 ± 0.15 g solids.100 g−1 DM. Mineral analysis revealed significant differences based on location. The concentrations of potassium exhibited a considerable elevation compared to those of magnesium, calcium, sodium, iron, and zinc. Moreover, the existence of diverse organic functional entities, including alcohols, ketones, and acids, was authenticated by Fourier-transform infrared spectroscopy. A differential distribution of the chemical composition of cladodes according to region was confirmed by nutritional, mineral and functional characterization and functional groups of cladodes. [ABSTRACT FROM AUTHOR]

Transforming growth factor β1 (TGF‐β) is a cytokine with pleiotropic biological functions. Recently, its signaling pathway has been highlighted for its implicative paradoxical roles in prostate cancer (PCa). Suppressing downstream effects of this pathway by interfering with receptor complex formation through inhibition of the TGF‐β1 leads to its antitumor effects, illuminating the TGF‐β1 as a viable therapeutic target for PCa. Our compound library—established by a literature‐based approach that identified phytochemicals with published evidence against the TGF‐β1—was screened by employing molecular docking, density functional theory (DFT), and molecular dynamic (MD) simulations to identify TGF‐β1 inhibitors. Eight of the 24 phytochemicals docked from our compound library had a good binding affinity (ranging from −11.7 to −10 kcal/mol) to the TGF‐β1 (PDB: 1PY5). The phytochemicals displayed good stability and reactivity as revealed by the DFT analysis and a desirable pharmacokinetic profile. The top four phytochemical complexes with high binding energies maintained stability throughout the 100 ns simulation. Qualitative studies on the drug repurposing attributes of bisindolylmaleimide, flavopiridol, baicalin, and gefitinib as inhibitors of TGF‐β1 are recommended; most importantly, suggest further wet‐lab studies to corroborate these phytochemicals—SB 202190, SB 203580, silymarin, and cryptotanshinone—in TGF‐β1 targeted drug development. [ABSTRACT FROM AUTHOR]

Pakistan is home to a rich rodent fauna, yet no investigations have been conducted on the presence of Haemogregarines in these animals, leaving their epidemiology and genetic diversity in this subtropical region unexplored. In this study, blood samples from four wild rodent species, Rattus (R.) rattus (n = 122), Mus (M.) musculus (n = 64), Rattus norvegicus (n = 57), and Dryomys nitedula (n = 1), were collected between May 2022 and July 2023 from three districts in Punjab and three in Khyber Pakhtunkhwa. PCR targeting a fragment of 600 base pairs from the 18 S rDNA gene revealed a 2.86% (7/244) prevalence of Haemogregarines in the rodents. DNA sequencing and BLAST analysis confirmed the presence of Hepatozoon spp. and Lankesterella spp. in the blood samples. Phylogenetic analysis indicated genetic diversity in the Pakistani sequences, which clustered with sequences found in reptiles, amphibians, birds, and mammals from various countries. The prevalence of the parasite varied among rodent species, with R. rattus showing the highest infection rate, followed by R. norvegicus and M. musculus. Female rodents were more frequently infected than males. Infected R. rattus exhibited significant disruptions in white blood cells, red blood cells, and platelet counts. Oxidative stress markers indicated elevated superoxide dismutase in the kidney, catalase in the heart, and malondialdehyde in the liver and lungs of infected rodents compared to uninfected ones. This study is an important contribution towards science as it the first report of Haemogregarines and Lankesterella spp. infections among Pakistani rodents. [ABSTRACT FROM AUTHOR]

Background Copper oxide (Cu2O) nanoparticles (CO NPs) are in extensive use during our everyday life as antimicrobial agent, lubricant, in manufacturing electrodes of lithium ion batteries as well as for photo catalytic degradation of organic pollutants. Due to extensive and diverse use Cu2O NPs, they are likely to accumulate in the environment and to affect the live forms. Present investigation was aimed to report the biocompatibility of CO NPs in Wistar rats in sex specific manner. CO NPs, having average diameter of 14.06 nm, were synthesized by co-precipitation method and scanning electron microscopy and X ray diffraction were used for their characterization. Methods For 14 consecutive days, Wistar rats (6 weeks old) of both sexes were intraperitoneally injected with 10 mg/mL saline/Kg body weight of CO NPs, while the control groups intraperitoneally received saline solution for same duration. Behavioral tests (open field and novel object recognition), complete blood count, selected biomarkers of oxidative stress and Copper concentration in brain and liver were determined in all subjects. Results High mortality rates [male 40% and female 60%] were observed in rats exposed to CO NPs. A sever decrease in body weight was also observed in both male and female rats exposed to CO NPs. Female rats treated with CO NPs spent significantly more time with novel object as compared to control [ P  = 0.05] during second trial of novel object test. CO NPs treated female rats had higher mean corpuscular hemoglobin [ P  < 0.001] levels and Copper concentration in liver [ P  = 0.04] than control. Male rats exposed to CO NPs had significantly higher mean corpuscular volume [ P  = 0.02] and superoxide dismutase [SOD] [ P  = 0.04] in lungs than their control group. All other studied parameters non significantly varied upon comparison between CO NPs treated and untreated rats of both sex. Conclusion In conclusion, we are reporting that intraperitoneal injections of CO NPs for 14 days can disturb complete blood count and biomarkers of oxidative stress in lungs of Wistar rats. [ABSTRACT FROM AUTHOR]

This study focused on developing an innovative, straightforward, and economical method utilizing a mixture of readily available solvents to extract arborescin (C2OH2OO8) crystals from Artemisia absinthium L. (A. absinthium). The structural elucidation and characterization were conducted using a suite of techniques including IR spectroscopy, CNHSO elemental analysis, scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM-EDS), and mass spectroscopy (MS). Density functional theory (DFT) calculations were employed to determine the molecular properties. Antioxidant activity was measured using the DPPH radical scavenging assay and the β-carotene bleaching test. Antimicrobial efficacy was assessed against four bacterial strains and three fungal strains. The molecular docking approach was employed to predict the probable binding patterns and affinities of arborescin with specific target biomolecules. Employing an array of analytical techniques, examination of the isolated crystal from A. absinthium. led to its comprehensive structural elucidation. IR spectroscopy revealed the presence of distinctive functional groups, including a carbonyl group within the γ-lactone and an epoxy group. CNHSO elemental analysis verified that the crystal contained only carbon, hydrogen, and oxygen, a finding corroborated by SEM-EDS analysis, consistent with the molecular structure of arborescin. Additionally, mass spectrometry confirmed the identity of the compound as arborescin, with a molecular ion with a mass m/z = 248. Quantum-Chemical Descriptors revealed that arborescin is resistant to elementary decomposition under standard conditions. Although arborescin demonstrates a relatively low antioxidant capacity, with an IC50 of 5.04 ± 0.12 mg/mL in the DPPH assay, its antioxidant activity in the β-carotene bleaching test was found to be 3.64%. Remarkably, arborescin effectively inhibits the growth of Staphylococcus aureus and Listeria innocua at low concentrations (MIC = 166 µg/mL). Additionally, it exhibits significant antifungal activity against Candida glabrata, with a minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 83 µg/mL and 166 µg/mL, respectively. In this study, arborescin exhibited a robust docking score of −8.1 kcal/mol, indicating a higher affinity compared to ciprofloxacin. This suggests that arborescin has significant potential as a potent antibacterial agent. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are pathological conditions in which the immune system mistakenly attacks its own tissues. This study evaluates the performance of two techniques, which are identifiers of autoantibody specifics: immunoblot and immunodot. This study was conducted in 300 patients of whom 62 were tested positive for antinuclear antibodies. The patients were initially screened for antinuclear antibodies using indirect immunofluorescence. Then, the identification of specific autoantibodies such as anti-extractable nuclear antigens (ENAs) was carried out using the immunoblot and immunodot techniques. The results showed that immunoblot and immunodot did not present a significant difference in their sensitivity against anti-SSA/52, SSB, CENP-B, PCNA, U1-snRNP, Jo-1, Pm-scl, and Mi-2 (p > 0.05). However, the two techniques showed a significant difference in their sensitivity toward autoantibodies anti-DNAn, anti-histone, anti-SmD1, and anti-ds-DNA (p < 0.05). The immunoblot data were in complete accordance with the immunodot data (100%) regarding the detection of autoantibodies such as anti SSA/52, SSB, CENP-B, PCNA, U1-snRP, Jo-1, Pm-scl, and Mi-2, 80% regarding SmD1, and 75% concerning ds-DNA. We should certainly pay closer attention to the efficiency of the techniques used in the diagnosis of autoimmune diseases.

Barbary fig called prickly pear is a plant belonging to family Cactaceae growing under hard climate conditions. A spiny variety of prickly pear named “Drbana” (Opuntia megacantha) and two non-spiny varieties named “Akria” and “Mlez” (Opuntia ficus-indica) growing in the Rhamna region (Morocco) were studied in terms of physicochemical characteristics. The physicochemical characterization (humidity, water activity, pH, total titratable acidity, Brix, and ash content) and the biochemical characterization (total carotenoid content, betalain content, total polyphenolic content, and ascorbic acid content) of the fruit pulp of prickly pear were performed according to the previously reported methods. The finding of physicochemical characterization of all studied varieties showed that the fruit pulp also contained an interesting bioactive compound classes in humidity, water activity, pH, total titratable acidity, Brix, and ash content. Regarding the biochemical characterization, the obtained finding showed the fruit pulp also contained an interesting bioactive compound classes particularly the total betalains, polyphenols, carotenoids, and ascorbic acids. Based on the obtained results in the current research work, we can affirm that the fruits of all studied varieties meet the requirement for being exploited in food, cosmetic, and pharmaceutical industries.

This document is a correction notice for an article titled "The antioxidant, antidiabetic, and antihyperlipidemic effects of the polyphenolic extract from Salvia Blancoana subsp. Mesatlantica on induced diabetes in rats." The correction states that an incorrect graphical abstract was published in the original article, and it has been corrected in both the correction notice and the original article. The correct version of the graphical abstract is provided in the correction notice. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are listed as Souad Maache, Hassan Laaroussi, Najoua Soulo, Ghizlane Nouioura, Nabil Boucetta, Mohammed Bouslamti, Hamza Saghrouchni, Yousef A. Bin Jardan, Samir Ibenmoussa, Mohammed Bourhia, Badiaa Lyoussi, and Ilham Elarabi. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Pakistan is home to a rich rodent fauna, yet no investigations have been conducted on the presence of Haemogregarines in these animals, leaving their epidemiology and genetic diversity in this subtropical region unexplored. In this study, blood samples from four wild rodent species, Rattus (R.) rattus (n = 122), Mus (M.) musculus (n = 64), Rattus norvegicus (n = 57), and Dryomys nitedula (n = 1), were collected between May 2022 and July 2023 from three districts in Punjab and three in Khyber Pakhtunkhwa. PCR targeting a fragment of 600 base pairs from the 18 S rDNA gene revealed a 2.86% (7/244) prevalence of Haemogregarines in the rodents. DNA sequencing and BLAST analysis confirmed the presence of Hepatozoon spp. and Lankesterella spp. in the blood samples. Phylogenetic analysis indicated genetic diversity in the Pakistani sequences, which clustered with sequences found in reptiles, amphibians, birds, and mammals from various countries. The prevalence of the parasite varied among rodent species, with R. rattus showing the highest infection rate, followed by R. norvegicus and M. musculus. Female rodents were more frequently infected than males. Infected R. rattus exhibited significant disruptions in white blood cells, red blood cells, and platelet counts. Oxidative stress markers indicated elevated superoxide dismutase in the kidney, catalase in the heart, and malondialdehyde in the liver and lungs of infected rodents compared to uninfected ones. This study is an important contribution towards science as it the first report of Haemogregarines and Lankesterella spp. infections among Pakistani rodents., Competing Interests: Declarations. Ethical approval: All experiments and animal handling procedures were approved by the Ethical Review Committee of Bahauddin Zakariya University, Multan, Pakistan (BZU/Ethics/Zool-29-2022). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)