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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 -
Environmental Science & Technology Apr 2024The limited research on volatile organic compounds (VOCs) has not taken into account the interactions between constituents. We used the weighted quantile sum (WQS) model...
The limited research on volatile organic compounds (VOCs) has not taken into account the interactions between constituents. We used the weighted quantile sum (WQS) model and generalized linear model (GLM) to quantify the joint effects of ambient VOCs exposome and identify the substances that play key roles. For a 0 day lag, a quartile increase of WQS index for -alkanes, iso/anti-alkanes, aromatic, halogenated aromatic hydrocarbons, halogenated saturated chain hydrocarbons, and halogenated unsaturated chain hydrocarbons were associated with 1.09% (95% CI: 0.13, 2.06%), 0.98% (95% CI: 0.22, 1.74%), 0.92% (95% CI: 0.14, 1.69%), 1.03% (95% CI: 0.14, 1.93%), 1.69% (95% CI: 0.48, 2.91%), and 1.85% (95% CI: 0.93, 2.79%) increase in cardiovascular disease (CVD) emergency hospital admissions, respectively. Independent effects of key substances on CVD-related emergency hospital admissions were also reported. In particular, an interquartile range increase in 1,1,1-trichloroethane, methylene chloride, styrene, and methylcyclohexane is associated with a greater risk of CVD-associated emergency hospital admissions [3.30% (95% CI: 1.93, 4.69%), 3.84% (95% CI: 1.21, 6.53%), 5.62% (95% CI: 1.35, 10.06%), 8.68% (95% CI: 3.74, 13.86%), respectively]. We found that even if ambient VOCs are present at a considerably low concentration, they can cause cardiovascular damage. This should prompt governments to establish and improve concentration standards for VOCs and their sources. At the same time, policies should be introduced to limit VOCs emission to protect public health.
Topics: Humans; Volatile Organic Compounds; Air Pollutants; Environmental Monitoring; Exposome; Cardiovascular Diseases; Hydrocarbons; Hydrocarbons, Halogenated; Hospitals
PubMed: 38502526
DOI: 10.1021/acs.est.3c08937 -
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 -
Fitoterapia Apr 2024Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative...
Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative inquiry encompassed the isolation of phytochemical components from the bark of Kopsia teoi, followed by the assessment of their α-amylase inhibition. The phytochemical composition of the K. teoi culminated in the discovery of a pair of new indole alkaloids; which are 16-epi-deacetylakuammiline N(4)-methylene chloride (akuammiline) (1), and N(1)-methoxycarbonyl-11-methoxy-12-hydroxy-Δ-kopsinine (aspidofractinine) (2), together with five known compounds i.e. kopsiloscine G (aspidofractinine) (3), akuammidine (sarpagine) (4), leuconolam (aspidosperma) (5), N-methoxycarbonyl-12-methoxy-Δ-kopsinine (aspidofractinine) (6), and kopsininate (aspidofractinine) (7). All compounds were determined via spectroscopic analyses. The in vitro evaluation against α-amylase showed good inhibitory activities for compounds 5-7 with the inhibitory concentration (IC) values of 21.7 ± 1.2, 34.1 ± 0.1, and 30.0 ± 0.8 μM, respectively compared with the reference acarbose (IC = 34.4 ± 0.1 μM). The molecular docking outputs underscored the binding interactions of compounds 5-7 ranging from -8.1 to -8.8 kcal/mol with the binding sites of α-amylase. Consequently, the outcomes highlighted the anti-hyperglycemic attributes of isolates from K. teoi.
Topics: Secologanin Tryptamine Alkaloids; Molecular Docking Simulation; alpha-Amylases; Molecular Structure; Indole Alkaloids; Phytochemicals; Apocynaceae
PubMed: 38417682
DOI: 10.1016/j.fitote.2024.105873 -
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 -
Computational Biology and Chemistry Apr 2024The exploration encompassed the synthesis and characterization of two innovative complexes, namely FePHNS and CuPHNS, employing a diverse array of analytical techniques...
Designing, DFT, biological, & molecular docking analysis of new Iron(III) & copper(II) complexes incorporating 1-{[-(2-Hydroxyphenyl)methylene]amino}-5,5-diphenylimidazolidine-2,4-dione (PHNS).
The exploration encompassed the synthesis and characterization of two innovative complexes, namely FePHNS and CuPHNS, employing a diverse array of analytical techniques such as elemental analysis, infrared and ultraviolet-visible spectroscopy, mass spectrometry, molar conductivity measurements, magnetic susceptibility assessments, and thermal analysis (TGA). In the spectral domain, infrared spectroscopy substantiated the tridentate ONS coordination of the PHNS ligand to the central metal atom. Thermal analysis offered valuable insights into the distribution and content of water molecules within the complexes. Density functional theory (DFT) calculations were harnessed to validate the molecular structures of both the PHNS ligand and its complex entities, providing an intricate comprehension of their quantum chemical parameters. The investigation extended to an evaluation of the in vitro antibacterial, antifungal, and antioxidant efficacy of the PHNS ligand and its complexes, revealing heightened biological activities for the complexes in comparison to the free PHNS ligand, notably with the CuPHNS complex demonstrating the highest activity, while the PHNS ligand exhibited the lowest. To delve into potential physiological activities, molecular docking studies were conducted, predicting the binding affinity of the compounds to proteins 2vf5 (Glucosamine-6-phosphate synthase in complex with glucosamine-6-phosphate) from Escherichia coli, 3cku (rate oxidase from Aspergillus flavus complexed with its inhibitor 8-azaxanthin and chloride) from Aspergillus flavus, and 5IJT (Crystal structure of Human Peroxiredoxin 2 Oxidized). The ensuing analysis of protein-ligand interactions and binding energies underscored the promising physiological activities of the investigated compounds, warranting further exploration for their potential in novel drug development.
Topics: Humans; Copper; Molecular Docking Simulation; Iron; Phenytoin; Ligands; Anti-Bacterial Agents; Spectrophotometry, Infrared; Microbial Sensitivity Tests
PubMed: 38382408
DOI: 10.1016/j.compbiolchem.2024.108031 -
Chemosphere Mar 2024The analysis of chlorinated paraffins (CPs) is today an analytical challenge. Indeed, it is still impractical to describe their real composition in terms of...
The analysis of chlorinated paraffins (CPs) is today an analytical challenge. Indeed, it is still impractical to describe their real composition in terms of polychlorinated alkanes (PCAs) homologue groups, which dominate technical mixtures. The co-elution of PCA congeners generates interferences due to the competition phenomena which occur during the ionisation process as well as to the dependence of the ionisation sources on the PCA chemistry. Therefore, the aim of this study was to investigate the influence of chromatographic separation, by LC-ESI-HRMS coupling, on the PCA homologue group pattern and, eventually, on their determination in food samples from interlaboratory studies. For this, three different mobile phases and six LC chromatographic columns were studied in order to optimise the analysis of CP mixtures. The first results showed that the use of a MeOH/HO mobile phase reveals more appropriately the higher chlorinated PCAs. However, using ACN/HO led to less ion species, with almost exclusively [M + Cl] adducts, formed using post-column dichloromethane addition. Regarding the choice of the stationary phases, Hypercarb column provided a completely different homologue group pattern from the other chromatographic columns, in relation with the stronger retention of PCAs. Among the other columns, the C30 column better highlighted the short-chain PCAs compared to the C18 column conventionally used. Because the regulations now concern short-chain CPs, the quantification of food samples was then carried out on the C30 column. The optimised LC-ESI-HRMS conditions using C30 column and MeOH/HO solvent mixture led to a quantification of PCAs in samples from interlaboratory studies with satisfactory accuracy (|Z-score| ≤ 2) and precision (<15%).
Topics: Paraffin; Hydrocarbons, Chlorinated; Mass Spectrometry; Chromatography, Liquid; Methylene Chloride; Alkanes
PubMed: 38346520
DOI: 10.1016/j.chemosphere.2024.141401 -
International Journal of Biological... Mar 2024This study aims to develop polylactic acid (PLA)-based packaging films with imparted antimicrobial properties and enhanced physical characteristics by evaluating the...
This study aims to develop polylactic acid (PLA)-based packaging films with imparted antimicrobial properties and enhanced physical characteristics by evaluating the likely interaction among multiple film components. For this purpose; epoxidized soybean oil (ES) (20 %) serves as a plasticizer, spruce resin (SR) (15 %) functions as both a plasticizer and antimicrobial agent, ZnO (0.1 %) acts as a nanofiller and antimicrobial, and finally thyme and clove essential oil mixture (5 % and 10 %) serves as an antimicrobial agent were incorporated to PLA film formulation. Composite materials were prepared by the solvent casting method using methylene chloride as the solvent. The developed films were characterized in terms of physical, mechanical, thermal, and antimicrobial properties. Tensile strength (59 MPa) and elastic modulus (2625 MPa) of the neat PLA film gradually decreased to 8.99 MPa and 725.4 MPa, respectively, with the sequential addition of all components, indicating enhanced flexibility. SR, ZnO, and EOs significantly imparted antimicrobial property to the PLA film as demonstrated by the inhibition zone of 13.83 mm and 15.67 mm observed for E. coli and S. aureus, respectively. The barrier properties of the films were enhanced by the addition of SR and ZnO; however, EOs increased the water vapor permeability from 0.080 to 0.090 g.mm/m.day.kPa compared to the neat PLA film. Principal component and hierarchical cluster analysis enabled the successful discrimination of the films, demonstrating how the film properties are affected by the film components. Therefore, this study suggests that selection of a proper combination is essential to highly benefit from the multicomponent film systems for designing alternative food packaging materials with desired properties.
Topics: Escherichia coli; Staphylococcus aureus; Zinc Oxide; Plasticizers; Anti-Infective Agents; Polyesters; Food Packaging; Solvents
PubMed: 38331069
DOI: 10.1016/j.ijbiomac.2024.129832 -
Journal of Ethnopharmacology May 2024Djibouti was a country where malaria has been endemic for centuries. The local population use the plants as repellents or first aid for uncomplicated malaria.
ETHNOPHARMACOLOGICAL RELEVANCE
Djibouti was a country where malaria has been endemic for centuries. The local population use the plants as repellents or first aid for uncomplicated malaria.
AIM OF THE STUDY
The aim was, for the first time, to collect and identify plants used by the local population to treat malaria and select the most interesting plants (those that are more commontly used, more available, and have fewer studies). These plants were evaluated for their antiplasmodial activity as well as their cytotoxicity on human cell lines for the most active ones.
MATERIALS AND METHODS
A semi-structured questionnaire was developed for this study to collect information about the use and identity of botanical drugs used to treat malaria. The use-reports (percentage) of each plant were recorded to determine their use importance. Also, the availability status of the plants was assessed; and those in critical condition were discarded excluded from further study. Fifteen plants, out of the 41 listed, were extracted with hydro alcohol, ethyl acetate, and dichloromethane for biological testing. Chloroquine-resistant strain FcB-1 of P. falciparum and a human diploid embryonic lung cell line were used for the antiplasmodial test, and to assess the cytotoxicity for human cells respectively. Preliminary analysis of extract constituents was carried out using thin layer chromatography (TLC).
RESULTS
This study identifies 41 plant taxa belonging to 32 families and records their use against malaria. Balanites rodunfolia, belonging to the Zygophyllaceae family, was the most commonly used plant, representing 44 % of use-reports. It was followed by Cadaba rodunfolia (15 %) from the Capparaceae family, and then the three species of Aloe: Aloe djiboutiensis (8.2 %), Aloe ericahenriettae (3.4 %), and Aloe rigens (3.4 %) from the Asphodelaceae family. The leaves are the most commonly used part of the plants to treat malaria, accounting for 76 % of usage. The preparation methods were decoction (52 %), maceration (29 %), and boiling (19 %). The administration routes were by oral (80 %), inhalation 19 %), and bathing (1 %). The best antiplasmodial activities were observed in the dichloromethane extracts of Cymbopogon commutatus and the ethyl acetate extracts of Aloe rigens and Terminalia brownii, with IC values of 9.8, 5, and 7.5 μg/mL, respectively. Their toxicity/activity levels were very favorable with selectivity indices of 5.6, 8.1, and 11.8 for C. commutatus, A. rigens, and T. Brownii, respectively.
CONCLUSION
Forty-one species of botanical drugs were listed as being used to treat malaria in Djibouti. All fifteen selected species showed antiplasmodial activity (IC < 50 μg/mL). This work will help guide the valorization of botanical drugs used to treat malaria in Djibouti.
Topics: Humans; Antimalarials; Plants, Medicinal; Pharmaceutical Preparations; Plant Extracts; Djibouti; Methylene Chloride; Malaria; Malaria, Falciparum; Aloe; Plasmodium falciparum
PubMed: 38310984
DOI: 10.1016/j.jep.2024.117839