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Molecules (Basel, Switzerland) May 2024We modified -symmetric benzene-1,3,5--amide (BTA) by introducing flexible linkers in order to generate an N-centered BTA (N-BTA) molecule. The N-BTA compound formed gels...
We modified -symmetric benzene-1,3,5--amide (BTA) by introducing flexible linkers in order to generate an N-centered BTA (N-BTA) molecule. The N-BTA compound formed gels in alcohols and aqueous mixtures of high-polar solvents. Rheological studies showed that the DMSO/water (1:1, /) gels were mechanically stronger compared to other gels, and a similar trend was observed for thermal stability. Powder X-ray analysis of the xerogel obtained from various aqueous gels revealed that the packing modes of the gelators in these systems were similar. The stimuli-responsive properties of the N-BTA towards sodium/potassium salts indicated that the gel network collapsed in the presence of more nucleophilic anions such as cyanide, fluoride, and chloride salts at the MGC, but the gel network was intact when in contact with nitrate, sulphate, acetate, bromide, and iodide salts, indicating the anion-responsive properties of N-BTA gels. Anion-induced gel formation was observed for less nucleophilic anions below the MGC of N-BTA. The ability of N-BTA gels to act as an adsorbent for hazardous anionic and cationic dyes in water was evaluated. The results indicated that the ethanolic gels of N-BTA successfully absorbed methylene blue and methyl orange dyes from water. This work demonstrates the potential of the N-BTA gelator to act as a stimuli-responsive material and a promising candidate for water purification.
PubMed: 38731640
DOI: 10.3390/molecules29092149 -
The Science of the Total Environment Jun 2024Parkinson's disease (PD) is a neurodegenerative disorder and leading cause of death worldwide, whose pathogenesis has been linked to toxic environmental exposures. We... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is a neurodegenerative disorder and leading cause of death worldwide, whose pathogenesis has been linked to toxic environmental exposures. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (i) to compile, and group by exposure setting (non-specified general; residential; occupational), environmental factors reported to modulate the risk of developing PD and (ii) to map and geospatially analyze global regions of both research activity and paucity. Among the broader environmental settings, occupational exposures had the highest average odds ratio value at 3.82, followed by general (non-specified or mixed) exposures at 3.07, and residential exposures at 2.36. Occupational exposure to industrial toxins was the highest ranked subset of exposures with an odds ratio of 10.74. Among the studies meeting the inclusion criteria, 75 % were conducted in Europe or the Western United States. The number of individuals partaking per study ranged from a high of 55,585 (Taiwan) to a low of 233 (Faroe Islands), with a mean of n = 14,462. The top three environmental factors associated with high odds ratios for increased risk of developing PD were (i) exposure to dyes (25.33), (ii) methylene chloride (16.5) and specifically in adult men (iii) consumption of fatty whale meat (10.57), which is known to harbor a broad spectrum of so called persistent, bioaccumulative, toxic (PBT) pollutants. Geospatially, the highest odds ratio values were identified in European countries, whereas notable data gaps were revealed for South America, Australia, Africa, and the majority of Asia with the exception of Taiwan. Whereas occupational exposures to industrial chemicals, such as harmful dyes and methylene chloride, ranked highest in risk values, available data suggest notable opportunities for reducing PD cases globally by limiting harmful environmental exposures to a spectrum of toxic chemicals, particularly via the food intake route. Thus, current efforts in improving environmental quality globally by limiting toxic emission may deliver the added benefit of helping to reign in PD. Agents of concern in this respect include pesticides (e.g., paraquat, demeton, monocrotophos), particulate matter associated with air pollution, and a spectrum of organic and inorganic neurotoxins including heavy metals.
Topics: Parkinson Disease; Humans; Environmental Exposure; Environmental Pollutants; Risk Factors; Occupational Exposure
PubMed: 38685425
DOI: 10.1016/j.scitotenv.2024.172838 -
BMC Complementary Medicine and Therapies Apr 2024Fabaceae plays a crucial role in African traditional medicine as a source of large number of important folk medication, agriculture and food plants. In a search of...
LC-MS/MS profiling of Tipuana tipu flower, HPLC-DAD quantification of its bioactive components, and interrelationships with antioxidant, and anti-inflammatory activity: in vitro and in silico approaches.
BACKGROUND
Fabaceae plays a crucial role in African traditional medicine as a source of large number of important folk medication, agriculture and food plants. In a search of potential antioxidant and anti-inflammatory candidates derived from locally cultivated plants, the flowers of Tipuana tipu (Benth.) Lillo growing in Egypt were subjected to extensive biological and phytochemical studies. The impact of the extraction technique on the estimated biological activities was investigated.
METHODS
The flowers were extracted using different solvents (aqueous, methanol, water/methanol (1:1), methanol/methylene chloride (1:1), and methylene chloride). The different extracts were subjected to antioxidant (DPPH, ABTS, and FRAP) and anti-inflammatory (COX-2 and 5-LOX) assays. The methanol extract was assessed for its inhibitory activity against iNOS, NO production, and pro-inflammatory cytokines (NF-KB, TNF-R, TNF-α, IL-1β, and IL-6) in LPS-activated RAW 264.7 macrophages. The composition-activity relationship of the active methanol extract was further investigated using a comprehensive LC-QTOF-MS/MS analysis. The major identified phenolic compounds were further quantified using HPLC-DAD technique. The affinity of representative compounds to iNOS, COX-2, and 5-LOX target active sites was investigated using molecular docking and molecular dynamics simulations.
RESULTS
The methanol extract exhibited the highest radical scavenging capacity and enzyme inhibitory activities against COX-2 and 5-LOX enzymes with IC values of 10.6 ± 0.4 and 14.4 ± 1.0 µg/mL, respectively. It also inhibited iNOS enzyme activity, suppressed NO production, and decreased the secretion of pro-inflammatory cytokines. In total, 62 compounds were identified in the extract including flavonoids, coumarins, organic, phenolic, and fatty acids. Among them 18 phenolic compounds were quantified by HPLC-DAD. The highest docking scores were achieved by kaempferol-3-glucoside and orientin. Additionally, molecular dynamics simulations supported the docking findings.
CONCLUSION
The flower could be considered a potentially valuable component in herbal medicines owing to its unique composition and promising bioactivities. These findings encourage increased propagation of T. tipu or even tissue culturing of its flowers for bioprospecting of novel anti-inflammatory drugs. Such applications could be adopted as future approaches that benefit the biomedical field.
Topics: Anti-Inflammatory Agents; Antioxidants; Plant Extracts; Flowers; Mice; Animals; RAW 264.7 Cells; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Molecular Docking Simulation; Egypt; Computer Simulation; Liquid Chromatography-Mass Spectrometry
PubMed: 38671392
DOI: 10.1186/s12906-024-04467-5 -
Gels (Basel, Switzerland) Mar 2024Developing gelled environmentally friendly dispersions in oil media is a hot topic for many applications. This study aimed to investigate the production of electrospun...
Developing gelled environmentally friendly dispersions in oil media is a hot topic for many applications. This study aimed to investigate the production of electrospun cellulose triacetate (CTA) nanofibers and to explore their potential application as a thickening agent for castor oil. The key factors in the electrospinning process, including the intrinsic properties of CTA solutions in methylene chloride (DCM)/ethanol (EtOH), such us the shear viscosity, surface tension, and electrical conductivity, were systematically studied. The impact of the CTA fiber concentration and the ratio of DCM/EtOH on the rheological properties of the gel-like dispersions in castor oil was then investigated. It was found that dispersions with a non-Newtonian response and above a critical concentration (5 wt.%), corresponding to approximately 2-2.5 times the entanglement concentration, are required to produce defect-free nanofibers. The average fiber diameter increased with CTA concentration. Further, the morphology and texture of the electrospun nanofibers are influenced by the ratio of solvents used. The rheological properties of dispersions are strongly influenced by the concentration and surface properties of nanofibers, such as their smooth or porous textures, which allow their modulation. Compared to other commonly used thickeners, such as synthetic polymers and metal soaps, CTA electrospun nanofibers have a much higher oil structuring capacity. This work illustrated the potential of using CTA nanofibers as the foundation for fabricating gel-like dispersions in oil media, and thus exerting hierarchical control of rheological properties through the use of a nanoscale fabrication technique.
PubMed: 38667640
DOI: 10.3390/gels10040221 -
Heliyon Apr 2024Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia...
The protective effects of methylene blue on astrocytic swelling after cerebral ischemia-reperfusion injuries are mediated by Aquaporin-4 and metabotropic glutamate receptor 5 activation.
Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia induced brain edema and its role in the inhibition of aquaporin 4 (AQP4) and metabotropic glutamate receptor 5 (mGluR5) expression. Rats were exposed 1 h transient middle cerebral artery occlusion (tMCAO), and MB was injected intravenously following reperfusion (3 mg/kg). Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 48 h after the onset of tMCAO to evaluate the brain infarction and edema. Brain tissues injuries as well as the glial fibrillary acidic protein (GFAP), AQP4 and mGluR5 expressions were detected. Oxygen and glucose deprivation/reoxygenation (OGD/R) was performed on primary astrocytes (ASTs) to induce cell swelling. MB was administered at the beginning of reoxygenation, and the perimeter of ASTs was measured by GFAP immunofluorescent staining. 3,5-dihydroxyphenylglycine (DHPG) and fenobam were given at 24 h before OGD to examine their effects on MB functions on AST swelling and AQP4 expression. MB remarkably decreased the volumes of T2WI and ADC lesions, as well as the cerebral swelling. Consistently, MB treatment significantly decreased GFAP, mGluR5 and AQP4 expression at 48 h after stroke. In the cultivated primary ASTs, OGD/R and DHPG significantly increased ASTs volume as well as AQP4 expression, which was reversed by MB and fenobam treatment. The obtained results highlight that MB decreases the post-ischemic brain swelling by regulating the activation of AQP4 and mGluR5, suggesting potential applications of MB on clinical ischemic stroke treatment.
PubMed: 38644842
DOI: 10.1016/j.heliyon.2024.e29483 -
Journal of Inorganic Biochemistry Jun 2024Our prior studies have illustrated that the uracil ruthenium(II) diimino complex, [Ru(Hucp)Cl(PPh)] (1)...
Our prior studies have illustrated that the uracil ruthenium(II) diimino complex, [Ru(Hucp)Cl(PPh)] (1) (Hucp = 2,6-bis-((6-amino-1,3-dimethyluracilimino)methylene)pyridine) displayed high hypoglycemic effects in diet-induced diabetic rats. To rationalize the anti-diabetic effects of 1, three new derivatives have been prepared, cis-[Ru(bpy)(urdp)]Cl (2) (urdp = 2,6-bis-((uracilimino)methylene)pyridine), trans-[RuCl(PPh)(urdp)] (3), and cis-[Ru(bpy)(Hucp)](PF) (4). Various physicochemical techniques were utilized to characterize the structures of the novel ruthenium compounds. Prior to biomolecular interactions or in vitro studies, the stabilities of 1-4 were monitored in anhydrous DMSO, aqueous phosphate buffer containing 2% DMSO, and dichloromethane (DCM) via UV-Vis spectrophotometry. Time-dependent stability studies showed ligand exchange between DMSO nucleophiles and chloride co-ligands of 1 and 3, which was suppressed in the presence of an excess amount of chloride ions. In addition, the metal complexes 1 and 3 are stable in both DCM and an aqueous phosphate buffer containing 2% DMSO. In the case of compounds 2 and 4 with no chloride co-ligands within their coordination spheres, high stability in aqueous phosphate buffer containing 2% DMSO was observed. Fluorescence emission titrations of the individual ruthenium compounds with bovine serum albumin (BSA) showed that the metal compounds interact non-discriminately within the protein's hydrophobic cavities as moderate to strong binders. The metal complexes were capable of disintegrating mature amylin amyloid fibrils. In vivo glucose metabolism studies in liver (Chang) cell lines confirmed enhanced glucose metabolism as evidenced by the increased glucose utilization and glycogen synthesis in liver cell lines in the presence of complexes 2-4.
Topics: Rats; Animals; Coordination Complexes; Serum Albumin, Bovine; Ruthenium; Dimethyl Sulfoxide; Hypoglycemic Agents; Chlorides; Diabetes Mellitus, Experimental; Pyridines; Peptides; Ruthenium Compounds; Glucose; Phosphates; Antineoplastic Agents; Ligands
PubMed: 38554578
DOI: 10.1016/j.jinorgbio.2024.112541 -
Scientific Reports Mar 2024Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main...
Leontodon hispidulus Boiss is a wild annual plant growing in Egypt. The present study aims for the first time, to evaluate the phytochemical profile of the main secondary metabolites of the optimized ethanolic extract of the plant using Quadrupole Time-of-Flight Liquid chromatography-mass spectrometry and Gas chromatography-mass spectrometry. It also aims to assess the anticancer activity of its different fractions against the prostate carcinoma cell line. Moreover, an in-silico docking study was performed using the Hexokinase-two enzyme. LC-qToF-MS analysis revealed the tentative identification of 36 phenolic compounds including the glycosides of (luteolin, quercetin, kaempferol, apigenin, isorhamnetin, and daidzein), coumarines (esculin, esculetin, and daphnetin), and phenolic acids (chlorogenic, caffeic, quinic, P-coumaric, and rosmarinic). GC-MS/MS analysis revealed the presence of 18 compounds where palmitic acid, myristic acid, alpha-amyrin, and beta-amyrin were the major ones. The cytotoxic activity results revealed that methylene chloride and ethyl acetate fractions showed the highest cytotoxic activity against the PC3 cell line, with IC values of 19, and 19.6 μg/ml, respectively. Interestingly, the docking study demonstrated that apigenin-7-O-glucoside, luteolin-7-O-glucoside, kaempferol-3-O-glucuronide, quercetin-4'-O-glucoside, esculin, rosmarinic acid, chlorogenic acid, and α-amyrin exhibited high affinity to the selected target, HEK-2 enzyme.
Topics: Tandem Mass Spectrometry; Apigenin; Quercetin; Hexokinase; Esculin; Plant Extracts; Glucosides; Asteraceae; Antioxidants; Pentacyclic Triterpenes
PubMed: 38519553
DOI: 10.1038/s41598-024-57288-4 -
Proceedings of the National Academy of... Mar 2024The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that regulates electrolyte and fluid balance in epithelial tissues. While activation...
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that regulates electrolyte and fluid balance in epithelial tissues. While activation of CFTR is vital to treating cystic fibrosis, selective inhibition of CFTR is a potential therapeutic strategy for secretory diarrhea and autosomal dominant polycystic kidney disease. Although several CFTR inhibitors have been developed by high-throughput screening, their modes of action remain elusive. In this study, we determined the structure of CFTR in complex with the inhibitor CFTR-172 to an overall resolution of 2.7 Å by cryogenic electron microscopy. We observe that CFTR-172 binds inside the pore near transmembrane helix 8, a critical structural element that links adenosine triphosphate hydrolysis with channel gating. Binding of CFTR-172 stabilizes a conformation in which the chloride selectivity filter is collapsed, and the pore is blocked from the extracellular side of the membrane. Single-molecule fluorescence resonance energy transfer experiments indicate that CFTR-172 inhibits channel gating without compromising nucleotide-binding domain dimerization. Together, these data reconcile previous biophysical observations and provide a molecular basis for the activity of this widely used CFTR inhibitor.
Topics: Cystic Fibrosis Transmembrane Conductance Regulator; Dimerization; Adenosine Triphosphate; Benzoates; Thiazolidines
PubMed: 38422021
DOI: 10.1073/pnas.2316675121 -
Scientific Reports Feb 2024Jatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin...
Jatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin conditions such as wound healing, as antibacterial and hemostatic. In this study, we evaluated the cytotoxicity and the antiviral activities of the methanolic J. variegata (leaves: Ext-1, stems: Ext-2, and roots: Ext-3), and J. spinosa extracts (aerial parts: Ext-4 and roots: Ext-5), in addition to their methylene chloride fractions of roots extracts (F-6 and F-7, respectively). All samples were tested against three human cancer cell lines in vitro (MCF-7, HepG2, and A549) and two viruses (HSV-2 and H1N1). Both plants showed significant cytotoxicity, among them, the methylene chloride fractions of roots of J. variegata (F-6) and J. spinosa roots (F-7) showed the highest activity on MCF-7 (IC = 1.4 and 1 μg/mL), HepG2 (IC = 0.64 and 0.24 μg/mL), and A549 (IC = 0.7 and 0.5 μg/mL), respectively, whereas the IC values of the standard doxorubicin were (3.83, 4.73, and 4.57 μg/mL) against MCF-7, HepG2, and A549, respectively. These results revealed that the roots of both plants are potential targets for cytotoxic activities. The in vitro results revealed potential antiviral activity for each of Ext-3, Ext-5, F-6, and F-7 against HVS-2 with IC of 101.23, 68.83, 4.88, 3.24 μg/mL and against H1N1 with IC of 51.29, 27.92, 4.24, and 3.06 μg/mL respectively, whereas the IC value of the standard acyclovir against HVS-2 was 83.19 μg/mL and IC value of the standard ribavirin against H1N1 was 52.40 μg/mL .The methanol extracts of the roots (Ext-3 and Ext-5) of both plants were characterized using UPLC/MS. A total of 73 metabolites were annotated, including fourteen diterpenoids, eleven flavonoids, ten phenolic acid conjugates, twelve fatty acids and their conjugates, five triterpenes and steroids, two sesquiterpenes, and six coumarins. The cytotoxicity and antiviral activities determined in the present work are explained by the existence of flavonoids, coumarins and diterpenes with commonly known cytotoxicity and antiviral activities.
Topics: Humans; Plant Extracts; Jatropha; Influenza A Virus, H1N1 Subtype; Methylene Chloride; Antineoplastic Agents; Flavonoids; Coumarins; Antiviral Agents
PubMed: 38418513
DOI: 10.1038/s41598-024-55196-1 -
Molecules (Basel, Switzerland) Feb 2024Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological...
Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological properties. In the search for new antiviral candidates, an in vitro screening against dengue virus (DENV) was performed on a series of dichloromethane and methanolic extracts prepared from six Asteraceae species, including , , , , , and , along with pure phytochemicals isolated from Asteraceae: mikanolide (), eupatoriopicrin (), eupahakonenin B (), minimolide (), estafietin (), 2-oxo-8-deoxyligustrin (), santhemoidin C (), euparin (), jaceidin (), nepetin (), jaceosidin (), eryodictiol (), eupatorin (), and 5-demethylsinensetin (). Results showed that the dichloromethane extracts of and and the methanolic extracts prepared from and were highly active and selective against DENV-2, affording EC values of 0.11, 0.15, 1.80, and 3.85 µg/mL, respectively, and SIs of 171.0, 18.8, >17.36, and 64.9, respectively. From the pool of phytochemicals tested, compounds , , and stand out as the most active (EC = 3.7, 3.1, and 6.8 µM, respectively; SI = 5.9, 6.7, and >73.4, respectively). These results demonstrate that Asteraceae species and their chemical constituents represent valuable sources of new antiviral molecules.
Topics: Plant Extracts; Asteraceae; Methylene Chloride; Phytochemicals; Antiviral Agents; Sesquiterpenes
PubMed: 38398567
DOI: 10.3390/molecules29040814