Evaluation of Antioxidant,Antibacterial and Enhancement of Antibiotic Action by Punica granatum Leaves Crude Extract and Enriched Fraction against Multidrug-Resistant Bacteria

The aim of this study was to evaluate the phytochemical composition, antioxidant, and antimicrobial potential of crude extract and fractions of Punica granatum leaves. The extract was produced by turbo extraction, after which hexanic, ethyl acetate, and aqueous fractions were obtained by partitioning. The chemical analyses were performed by thin layer chromatography and high-performance liquid chromatography, and the antioxidant activities were assayed by DPPH^. and ABTS^.+. Minimal inhibitory and bactericidal concentrations (MIC/MBC) were applied to twenty-two bacteria. Most strains susceptible to extract/fractions and resistant to antibiotics were selected, and ampicillin, azithromycin, ciprofloxacin, and gentamicin were associated with the ethyl acetate fraction (EAF) against multidrug-resistant strains in modulatory and checkboard models. The data from chromatographic analyses showed flavonoids and tannins in the extract, as well as the enrichment of EAF in phenols, mainly flavonoids. The flavonoids were connected to the electron transfer activity demonstrated in the DPPH^. and ABTS^.+ assays. Gram-positive strains are more susceptible to EAF. The subinhibitory concentrations of P. granatum enhanced the antimicrobial activity of the agents and reduced the EAF individual MIC, and the combination of EAF and antibiotics demonstrated a synergistic effect. These results present a promising approach for developing a therapy in which antioxidant extracts and fractions can be used in combination with antibiotics.     

Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase

Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250 million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with in vitro schistosomicidal activity, has not been in vivo evaluated against Schistosoma. In this work, we evaluated the in vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S. mansoni NTPDase 1 and S. mansoni NTPDase 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400 mg/kg) showed efficacy against S. mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three-dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S. mansoni NTPDases.     

Trypanocidal Activity of Dysphania ambrosioides,Lippia alba,and Tetradenia riparia Essential Oils against Trypanosoma cruzi

Despite the current treatments against Chagas Disease (CD), this vector-borne parasitic disease remains a serious public health concern. In this study, we have explored the in vitro and/or in vivo trypanocidal and cytotoxic activities of the essential oils (EOs) obtained from Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) (DA-EO), Lippia alba (Mill.) N.E. Brown (Verbenaceae) (LA-EO), and Tetradenia riparia (Hochst.) Codd (Lamiaceae) (TR-EO) grown in Brazil Southeast. DA-EO was the most active against the trypomastigote and amastigote forms in vitro; the IC₅₀ values were 8.7 and 12.2 μg mL⁻¹, respectively. The EOs displayed moderate toxicity against LLCMK2 cells, but the DA-EO showed high selectivity index (SI) for trypomastigote (SI=33.2) and amastigote (SI=11.7) forms. Treatment with 20 mg/kg DA-EO, LA-EO, or TR-EO for 20 days by intraperitoneal administration reduced parasitemia by 6.36 %, 4.74 %, and 32.68 % on day 7 and by 12.04 %, 27.96 %, and 65.5 % on day 9. These results indicated that DA-EO, LA-EO, and TR-EO have promising trypanocidal potential in vitro, whereas TR-EO has also potential trypanocidal effects in vivo.     

Synthetic Aurones: New Features for Schistosoma mansoni Therapy

In this work, two synthetic aurones revealed moderate schistosomicidal potential in in vitro and in vivo assays. Aurones ( 1 ) and ( 2 ) promoted changes in tegument integrity and motor activity, leading to death of adult Schistosoma mansoni worms in in vitro assays. When administered orally (two doses of 50 mg/kg) in experimentally infected animals, synthetic aurones ( 1 ) and ( 2 ) promoted reductions of 56.20 % and 57.61 % of the parasite load and stimulated the displacement towards the liver of the remaining adult worms. The oogram analysis revealed that the treatment with both aurones interferes with the egg development kinetics in the intestinal tissue. Seeking an action target for compounds ( 1 ) and ( 2 ), the connection with NTPDases enzymes, recognized as important therapeutic targets for S. mansoni, was evaluated. Molecular docking studies have shown promising results. The dataset reveals the anthelmintic character of these compounds, which can be used in the development of new therapies for schistosomiasis.     

Computer-Guided Trypanocidal Activity of Natural Lactones Produced by Endophytic Fungus of Euphorbia umbellata

Hundreds of millions of people worldwide are affected by Chagas’ disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC₅₀ values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (−3.38), corroborating with IC₅₀ assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development.     

Morphological and Chemical Differentiation between Tunisian Populations of Pinus halepensis,Pinus brutia,and Pinus pinaster

The lipid fraction of seeds from different pine species and populations was studied regarding total lipid content, fatty acid profile and vitamin E composition. The investigated seeds contained a high percentage of lipid (13.6 to 31.5 %). Lipid fractions were found to be rich in vitamin E, which varied significantly among species and populations. P. halepensis (Ph−Hn) showed the highest content of vitamin E (256.3 mg/kg of seeds) and the uppermost content of α-tocopherol (44 mg/kg). However, P. halepensis (Ph−Kas) was the richest in γ-tocopherol (204.9 mg/kg). Lipid fractions had a low content of δ-tocopherol (1.2 to 3.6 mg/kg. The highest content of γ-tocotrienol (∼18 %) was determined for P. halepensis (Ph−Dc and Ph−Hn). Thirteen fatty acids were identified by GC-FID with significant variation between the investigated species. The linoleic acid was the major fatty acid followed by oleic acid and palmitic acid. The chemical differentiation among species for the composition of fatty acids and vitamin E was confirmed by PCA. Significant correlations were observed between the content of vitamin E and fatty acids and ecological parameters of P. halepensis populations.     

Direct response of tree growth to soil water and its implications for terrestrial carbon cycle modelling

Wood growth constitutes the main process for long‐term atmospheric carbon sequestration in vegetation. However, our understanding of the process of wood growth and its response to environmental drivers is limited. Current dynamic global vegetation models (DGVMs) are mainly photosynthesis‐driven and thus do not explicitly include a direct environmental effect on tree growth. However, physiological evidence suggests that, to realistically model vegetation carbon allocation under increased climatic stressors, it is crucial to treat growth responses independently from photosynthesis. A plausible growth response function suitable for global simulations in DGVMs has been lacking. Here, we present the first soil water‐growth response function and parameter range for deciduous and evergreen conifers. The response curve was calibrated against European larch and Norway spruce in a dry temperate forest in the Swiss Alps. We present a new data‐driven approach based on a combination of tree ring width (TRW) records, growing season length and simulated subdaily soil hydrology to parameterize ring width increment simulations. We found that a simple linear response function, with an intercept at zero moisture stress, used in growth simulations reproduced 62.3% and 59.4% of observed TRW variability for larch and spruce respectively and, importantly, the response function slope was much steeper than literature values for soil moisture effects on photosynthesis and stomatal conductance. Specifically, we found stem growth stops at soil moisture potentials of ?0.47 MPa for larch and ?0.66 MPa for spruce, whereas photosynthesis in trees continues down to ?1.2 MPa or lower, depending on species and measurement method. These results are strong evidence that the response functions of source and sink processes are indeed very different in trees, and need to be considered separately to correctly assess vegetation responses to environmental change. The results provide a parameterization for the explicit representation of growth responses to soil water in vegetation models.