RESUMO
This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. Organogel nanoparticles with seed oil (SON) or with resveratrol entrapped in the seed oil (RSON) formed functional organogel nanoparticles that showed a particle size <100 nm, polydispersity index <0.3, negative zeta potential, and maintenance of electrical conductivity. The resveratrol entrapment efficiency in RSON was 99 ± 1%. The seed oil and SON showed no cytotoxicity against human non-tumor cells or tumor cells. Resveratrol at 50 µg/mL was cytotoxic for non-tumor cells, and was cytotoxic for tumor cells at 25 µg/mL. Resveratrol entrapped in RSON showed a decrease in cytotoxicity against non-tumor cells and cytotoxic against tumor cells at 50 µg/mL. Thus, SON is a potential new platform for the delivery of resveratrol with selective cytotoxic activity in the treatment of melanoma.
Assuntos
Antineoplásicos , Arecaceae , Melanoma , Nanogéis , Sistemas de Liberação de Fármacos por Nanopartículas , Óleo de Palmeira , Resveratrol , Resveratrol/administração & dosagem , Melanoma/terapia , Humanos , Linhagem Celular Tumoral , Nanogéis/administração & dosagem , Nanogéis/química , Arecaceae/química , Óleo de Palmeira/química , Sementes/química , Tamanho da Partícula , Antineoplásicos/administração & dosagem , Antineoplásicos/químicaRESUMO
Myrcia bella is a medicinal plant used for the treatment of diabetes, hemorrhages, and hypertension in Brazilian folk medicine. Considering that plant extracts are attractive sources of new drugs, the aim of the present study was to verify the influence of incorporating 70% hydroalcoholic of M. bella leaves in nanostructured lipid systems on the mutagenic and antifungal activities of the extract. In this work, we evaluated the antifungal potential of M. bella loaded on the microemulsion against Candida sp for minimum inhibitory concentration, using the microdilution technique. The system was composed of polyoxyethylene 20 cetyl ether and soybean phosphatidylcholine (10%), grape seed oil, cholesterol (10%: proportion 5/1), and purified water (80%). To investigate the mutagenic activity, the Ames test was used with the Salmonella Typhimurium tester strains. M. bella, either incorporated or free, showed an important antifungal effect against all tested strains. Moreover, the incorporation surprisingly inhibited the mutagenicity presented by the extract. The present study attests the antimicrobial properties of M. bella extract, contributing to the search for new natural products with biological activities and suggesting caution in its use for medicinal purposes. In addition, the results emphasize the importance of the use of nanotechnology associated with natural products as a strategy for the control of infections caused mainly by the genus Candida sp.
Assuntos
Myrtaceae , Plantas Medicinais , Antifúngicos/farmacologia , Mutagênicos , Extratos Vegetais/farmacologiaRESUMO
Considering the promising previous results of Cu (II) complexes with isoniazid active ligand against Mycobacterium tuberculosis, the main causative agent of tuberculosis, novel biological assays evaluating its toxicogenic potential were performed to ensure the safe use. The genotoxicity/mutagenicity of the complexes CuCl2(INH)2.H2O (I1), Cu(NCS)2(INH)2.5H2O (I2) and Cu(NCO)2(INH)2.4H2O (I3) was evaluated by the Comet, Micronucleus-cytome and Salmonella microsome (Ames test) assays. The cell viability using resazurin assay indicated that I1, I2 e I3 had moderate to low capacity to reduce the viability of colorectal cells (Caco-2), liver cells (HepG2), lung cells (GM 07492-A and A549) and endothelial cells (HU-VE-C). On genotoxicity/mutagenicity, I1 complex did not induce sizable levels of DNA damage in HepG2 cells (Comet assay), and gene (Ames test) and chromosomal (Micronucleus-cytome assay) mutations. Already, I2 and I3 complexes were considered mutagenic in the highest concentrations used. In light of the above, these results contribute to valuable data on the safe use of Cu(II) complexes. Considering the absence of mutagenicity and cytotoxicity of I1, this complex is a potential candidate for the development of a new drug to the treatment tuberculosis, while I2 and I3 require caution in its use.
Assuntos
Antituberculosos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Células A549 , Antituberculosos/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complexos de Coordenação/química , Cobre/química , Células Hep G2 , Humanos , Isoniazida/química , Ligantes , Testes de Sensibilidade Microbiana , Conformação Molecular , Testes de Mutagenicidade , Mycobacterium tuberculosis/citologiaRESUMO
Copaifera langsdorffii L. is one of the most known medicinal species in Brazil. Its leaves are rich in phenolic compounds with potential biological activities as an antioxidant and chelating agent. This paper reports the isolation of four compounds from the hydroalcoholic extract of the leaves of C. langsdorffii and the investigation of their possible cytoprotective effects against heavy metal poisoning. Quercitrin (1), afzelin (2), 3,5-di-O-(3-O-methyl galloyl) quinic acid (3) and 4,5-di-O-(3-O-methyl galloyl) quinic acid (4), were associated with toxic doses of methylmercury and lead and evaluated by Alamar blue cell viability assays in HepG2 and PC12. The compounds displayed significant cytoprotective effect for the HepG2 cell line against both metals. Compounds 1-4 did not protect PC12 cells against methylmercury induced-cytotoxicity, but at lower concentrations, they protected against lead induced-cytotoxicity. The evaluated compounds showed a promising cytoprotection effect against exposure to heavy metals and should be further investigated as protective agents.
Assuntos
Fabaceae/química , Intoxicação por Metais Pesados/tratamento farmacológico , Compostos de Metilmercúrio/antagonistas & inibidores , Extratos Vegetais/farmacologia , Substâncias Protetoras/isolamento & purificação , Animais , Antioxidantes , Brasil , Linhagem Celular , Intoxicação por Metais Pesados/prevenção & controle , Humanos , Chumbo/toxicidade , Intoxicação por Chumbo/tratamento farmacológico , Intoxicação por Chumbo/prevenção & controle , Manosídeos , Intoxicação por Mercúrio/tratamento farmacológico , Intoxicação por Mercúrio/prevenção & controle , Compostos de Metilmercúrio/toxicidade , Fenóis , Folhas de Planta/química , Proantocianidinas , Substâncias Protetoras/farmacologia , Quercetina/análogos & derivados , Ácido Quínico , RatosRESUMO
Copaifera trapezifolia Hayne occurs in the Atlantic Rainforest, which is considered one of the most important and endangered tropical forests on the planet. Although literature works have described many Copaifera spp., their biological activities remain little known. In the present study, we aimed to evaluate (1) the potential of the hydroalcoholic extract from C. trapezifolia leaves (CTE) to act against the causative agents of tooth decay and apical periodontitis and (2) the cytotoxicity and mutagenicity of CTE to ensure that it is safe for subsequent application. Concerning the tested bacteria, the MIC and the minimum bactericidal concentration of CTE varied between 100 and 400 µg ml-1. The time-kill assay conducted at a CTE concentration of 100 µg ml-1 evidenced bactericidal activity against Porphyromonas gingivalis (ATCC 33277) and Peptostreptococcus micros (clinical isolate) within 72 h. CTE at 200 µg ml-1 inhibited Porphyromonas gingivalis and Peptostreptococcus micros biofilm formation by at least 50 %. A combination of CTE with chlorhexidine dichlorohydrate did not prompt any synergistic effects. The colony-forming assay conducted on V79 cells showed that CTE was cytotoxic at concentrations above 156 µg ml-1. CTE exerted mutagenic effect on V79 cells, but the micronucleus test conducted on Swiss mice and the Ames test did not reveal any mutagenicity. Therefore, the use of standardized and safe extracts could be an important strategy to develop novel oral care products with antibacterial action. These extracts could also serve as a source of compounds for the discovery of new promising biomolecules.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/toxicidade , Produtos Biológicos/farmacologia , Produtos Biológicos/toxicidade , Fabaceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Animais , Antibacterianos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Testes de Mutagenicidade , Peptostreptococcus/efeitos dos fármacos , Peptostreptococcus/fisiologia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/fisiologiaRESUMO
Tuberculosis is a top infectious disease killer worldwide, caused by the bacteria Mycobacterium tuberculosis. Increasing incidences of multiple drug-resistance (MDR) strains are emerging as one of the major public health threats. However, the drugs in use are still incapable of controlling the appalling upsurge of MDR. In recent years a marked number of research groups have devoted their attention toward the development of specific and cost-effective antimicrobial agents against targeted MDR-Tuberculosis. In previous studies, ruthenium(II) complexes (SCAR) have shown a promising activity against MDR-Tuberculosis although few studies have indeed considered ruthenium toxicity. Therefore, within the preclinical requirements, we have sought to determine the cyto-genotoxicity of three SCAR complexes in this present study. The treatment with the SCARs induced a concentration-dependent decrease in cell viability in CHO-K1 and HepG2 cells. Based on the clonogenic survival, SCAR 5 was found to be more cytotoxic while SCAR 6 exhibited selectivity action on tumor cells. Although SCAR 4 and 5 did not indicate any mutagenic activity as evidenced by the Ames and Cytokinesis block micronucleus cytome assays, the complex SCAR 6 was found to engender a frameshift mutation detected by Salmonella typhimurium in the presence of S9. Similarly, we observed a chromosomal damage in HepG2 cells with significant increases of micronuclei and nucleoplasmic bridges. These data indicate that SCAR 4 and 5 complexes did not show genotoxicity in our models while SCAR 6 was considered mutagenic. This study presented a comprehensive genotoxic evaluation of SCAR complexes were shown to be genotoxic in vitro. All in all, further studies are required to fully elucidate how the properties can affect human health.
Assuntos
Antituberculosos/toxicidade , Complexos de Coordenação/toxicidade , Mutagênicos/toxicidade , Rutênio/toxicidade , Animais , Células CHO , Cricetulus , Citocinese/efeitos dos fármacos , Células Hep G2 , Humanos , Testes para Micronúcleos , Rutênio/química , Salmonella typhimurium/efeitos dos fármacosRESUMO
Caesalpinia ferrea Martius has traditionally been used in Brazil for many medicinal purposes, such as the treatment of bronchitis, diabetes and wounds. Despite its use as a medicinal plant, there is still no data regarding the genotoxic effect of the stem bark. This present work aims to assess the qualitative and quantitative profiles of the ethanolic extract from the stem bark of C. ferrea and to evaluate its mutagenic activity, using a Salmonella/microsome assay for this species. As a result, a total of twenty compounds were identified by Flow Injection Analysis Electrospray Ionization Ion Trap Mass Spectrometry (FIA-ESI-IT-MS/MSn) in the ethanolic extract from the stem bark of C. ferrea. Hydrolyzable tannins predominated, principally gallic acid derivatives. The HPLC-DAD method was developed for rapid quantification of six gallic acid compounds and ellagic acid derivatives. C. ferrea is widely used in Brazil, and the absence of any mutagenic effect in the Salmonella/microsome assay is important for pharmacological purposes and the safe use of this plant.
Assuntos
Caesalpinia/química , Mutagênicos/química , Mutagênicos/farmacologia , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Estrutura MolecularRESUMO
BACKGROUND: In various regions of Brazil, several species of the genus Byrsonima (Malpighiaceae) are widely used to treat gastrointestinal complications. This genus has about 150 species of shrubs and trees distributed over the entire Neotropical region. Various biological activities have been identified in these plants, especially antioxidant, antimicrobial and topical and systemic anti-inflammatory activities. The aim of this study was to investigate the mutagenicity and antimutagenicity of hydroalcoholic leaf extracts of six species of Byrsonima: B. verbascifolia, B. correifolia, B. coccolobifolia, B. ligustrifolia, B. fagifolia and B. intermedia by the Salmonella microsome assay (Ames test). METHODS: Mutagenic and antimutagenic activity was assessed by the Ames test, with the Salmonella typhimurium tester strains TA100, TA98, TA97a and TA102, with (+S9) and without (-S9) metabolization, by the preincubation method. RESULTS: Only B. coccolobifolia and B. ligustrifolia showed mutagenic activity. However, the extracts of B. verbascifolia, B. correifolia, B. fagifolia and B. intermedia were found to be strongly antimutagenic against at least one of the mutagens tested. CONCLUSIONS: These results contribute to valuable data on the safe use of medicinal plants and their potential chemopreventive effects. Considering the excellent antimutagenic activities extracted from B. verbascifolia, B. correifolia, B. fagifolia and B. intermedia, these extracts are good candidate sources of chemopreventive agents. However, B. coccolobifolia and B. ligustrifolia showed mutagenic activity, suggesting caution in their use.