Anti-Trypanosoma cruzi Potential of Vestitol Isolated from Lyophilized Red Propolis.

Chagas disease (CD) is a worldwide public health problem, and the drugs available for its treatment have severe limitations. Red propolis is a natural extract known for its high content of phenolic compounds and for having activity against T. cruzi. The aim of this study was to investigate the trypanocidal potential of red propolis to isolate, identify, and indicate the mode of action of the bioactive compounds. The results revealed that the total phenolic content was 15.4 mg GAE/g, and flavonoids were 7.2 mg QE/g. The extract was fractionated through liquid-liquid partitioning, and the trypanocidal potential of the samples was evaluated using the epimastigote forms of the Y strain of T. cruzi. In this process, one compound was characterized by MS, 1H, and 13C NMR and identified as vestitol. Cytotoxicity was evaluated employing MRC-5 fibroblasts and H9C2 cardiomyocytes, showing cytotoxic concentrations above 15.62 µg/mL and 31.25 µg/mL, respectively. In silico analyses were applied, and the data suggested that the substance had a membrane-permeation-enhancing effect, which was confirmed through an in vitro assay. Finally, a molecular docking analysis revealed a higher affinity of vestitol with farnesyl diphosphate synthase (FPPS). The identified isoflavan appears to be a promising lead compound for further development to treat Chagas disease.

Evaluation of Anti-Candida albicans Activity and Release of Ketoconazole in PMMA-G-PEG 4000 Films.

Modified release systems depend on the selection of an appropriate agent capable of controlling the release of the drug, sustaining the therapeutic action over time, and/or releasing the drug at the level of a particular tissue or target organ. Polyethylene glycol 4000 (PEG 4000) is commonly employed in drug release formulations while polymethyl methacrylate (PMMA) is non-toxic and has a good solubility in organic solvents. This study aimed at the incorporation of ketoconazole in PMMA-g-PEG 4000 and its derivatives, thus evaluating its release profile and anti-Candida albicans and cytotoxic activities. Ketoconazole was characterized and incorporated into the copolymers. The ketoconazole incorporated in the copolymer and its derivatives showed an immediate release profile. All copolymers with ketoconazole showed activity against Candida albicans and were non-toxic to human cells in the entire concentration tested.

Naringin: antitumor potential in silico and in vitro on bladder cancer cells

Introduction: Urothelial carcinoma is a significant public health problem. Transitional cell carcinoma (TCC) is the most common subtype, accounting for approximately 90 % of all bladder cancers. Chemotherapeutic protocols have been studied, but some present high toxicity and low tolerability. Naringin is a polyphenolic compound found mainly in citrus fruits, which antitumor activity has been studied in several types of cancer. However, there is little information about naringin effects on bladder cancer. This study aimed to evaluate the antitumor potential of naringin in silico and in vitro using two bladder cancer cell lines. Method: In silico analysis was carried out by PASS Online software. In vitro , the effects of naringin treatment (12.5 - 400 µM) were evaluated regarding its cytotoxicity, clonogenic survival, morphological alterations, cell cycle progression, migration, and mutagenicity Results: In silico analyses predicted antitumor activity through several mechanisms of action. In vitro results showed naringin presented cytotoxic effects, reduced the number of colonies, inhibited cell migration, and changed the morphology and cell cycle progression of the two cell lines evaluated. However, naringin did not present mutagenic effects. Conclusions: Naringin has antiproliferative activity and is a promising candidate for bladder cancer treatment.(AU)

Introducción: El carcinoma urotelial es un problema de salud pública importante. El carcinoma de células de transición es el subtipo más común y representa aproximadamente el 90 % de todos los cánceres de vejiga. Se han estudiado protocolos quimioterapéuticos, pero algunos presentan alta toxicidad y baja tolerabilidad. La naringina es un compuesto polifenólico que se encuentra principalmente en los cítricos, cuya actividad antitumoral se ha estudiado en varios tipos de cáncer. Sin embargo, hay poca información sobre los efectos de la naringina en el cáncer de vejiga. Este estudio tuvo como objetivo evaluar el potencial antitumoral de la naringina in silico e in vitro utilizando dos líneas celulares de cáncer de vejiga. Método: El análisis in silico se llevó a cabo mediante el software PASS Online. In vitro, se evaluaron los efectos del tratamiento con naringina (12,5 - 400 µM) en cuanto a su citotoxicidad, supervivencia clonogénica, alteraciones morfológicas, progresión del ciclo celular, migración y mutagenicidad. Resultados: los análisis in silico predijeron la actividad antitumoral a través de varios mecanismos de acción. Los resultados in vitro mostraron que la naringina presentó efectos citotóxicos, redujo el número de colonias, inhibió la migración celular y cambió la morfología y la progresión del ciclo celular de las dos líneas celulares evaluadas. Sin embargo, la naringina no presentó efectos mutagénicos. Conclusiones: la naringina tiene actividad antiproliferativa y es un candidato prometedor para el tratamiento del cáncer de vejiga.(AU)

Antibacterial substances from leaves of Protium spruceanum (Burseraceae): in vitro and in silico evaluation

Due to the increase of bacterial resistance, the search for new antibiotics is necessary and the medicinal plants represent its most important source. The aim of this study was to evaluate the antibacterial property of extract and fractions from Protium spruceanum leaves, against pathogenic bacteria. By means of diffusion and microdilution assays, the crude extract was active against the nine bacteria tested being the hydromethanolic fraction the most active. During phytochemical procedures, procyanidin (1) and catechin (2) were identified as the main antibacterial constituents of this fraction. In silico results obtained using PASSonline tool indicated 1 and 2 as having good potential to interact with different targets of currently used antibiotics. These results no indicated potential to none DNA effect and indicated the cell wall as mainly target. Electrophoresis result supported that had no DNA damage. Cell wall damage was confirmed by propidium iodide test that showed increased membrane permeability and by cell surface deformations observed in scanning electronic microscopy. The in vitro assays together with the in silico prediction results establish the potential of P. spruceanum as source of antibacterial compounds that acts on important bacterial targets. These results contribute to the development of natural substances against pathogenic bacteria and to discovery of new antibiotics.

Antibacterial activity of extract and fractions from branches of Protium spruceanum and cytotoxicity on fibroblasts.

The crude ethanol extract (CEE) and fractions from branches of Protium spruceanum were subjected to antibacterial and cytotoxicity assays. Compounds of the most active fraction were identified by GC-MS and LC-MS. CEE was active against 19 bacteria and the ethyl acetate fraction (EAF) showed the lowest minimum bactericidal concentration (MBC 0.3-80.0 mg/mL). Through time-kill assay was observed that EAF induced rapid bactericidal effect against Staphylococcus saprophyticus. The cytotoxicity tests against L929 fibroblasts showed great potential of EAF on the treatment of infections caused by five bacteria (MBC < IC50). The results provide in vitro scientific support to the possible application of branches of P. spruceanum as antimicrobial agent that may contribute for treatment of infections.

Baccharis trimera inhibits reactive oxygen species production through PKC and down-regulation p47 phox phosphorylation of NADPH oxidase in SK Hep-1 cells.

Baccharis trimera, popularly known as "carqueja", is a native South-American plant possessing a high concentration of polyphenolic compounds and therefore high antioxidant potential. Despite the antioxidant potential described for B. trimera, there are no reports concerning the signaling pathways involved in this process. So, the aim of the present study was to assess the influence of B. trimera on the modulation of PKC signaling pathway and to characterize the effect of the nicotinamide adenine dinucleotide phosphate oxidase enzyme (NOX) on the generation of reactive oxygen species in SK Hep-1 cells. SK-Hep 1 cells were treated with B. trimera, quercetin, or rutin and then stimulated or not with PMA/ionomycin and labeled with carboxy H2DCFDA for detection of reactive oxygen species by flow cytometer. The PKC expression by Western blot and enzyme activity was performed to evaluate the influence of B. trimera and quercetin on PKC signaling pathway. p47 phox and p47 phox phosphorylated expression was performed by Western blot to evaluate the influence of B. trimera on p47 phox phosphorylation. The results showed that cells stimulated with PMA/ionomycin (activators of PKC) showed significantly increased reactive oxygen species production, and this production returned to baseline levels after treatment with DPI (NOX inhibitor). Both B. trimera and quercetin modulated reactive oxygen species production through the inhibition of PKC protein expression and enzymatic activity, also with inhibition of p47 phox phosphorylation. Taken together, these results suggest that B. trimera has a potential mechanism for inhibiting reactive oxygen species production through the PKC signaling pathway and inhibition subunit p47 phox phosphorylation of nicotinamide adenine dinucleotide phosphate oxidase.