RESUMO
The bark extract from Endopleura uchi has been widely used in traditional medicine to treat gynecological-related disorders, diabetes, and dyslipidemias albeit without scientific proof. In addition, E. uchi bark extract safety, especially regarding mutagenic activities, is not known. The aim of this study was to determine the chemical composition, antitumor, and toxicological parameters attributed to an E. uchi bark aqueous extract. The phytochemical constitution was assessed by colorimetric and chromatographic analyzes. The antiproliferative effect was determined using sulforhodamine B (SRB) assay using 4 cancer cell lines. Cytotoxic and genotoxic activities were assessed utilizing MTT and comet assays, respectively, while mutagenicity was determined through micronucleus and Salmonella/microsome assays. The chromatographic analysis detected predominantly the presence of gallic acid and isoquercitrin. The antiproliferative effect was more pronounced in human colon adenocarcinoma (HT-29) and human breast cancer (MCF-7) cell lines. In the MTT assay, the extract presented an IC50 = 39.1 µg/ml and exhibited genotoxic (comet assay) and mutagenic (micronucleus test) activities at 20 and 40 µg/ml in mouse fibroblast cell line (L929) and mutagenicity in the TA102 and TA97a strains in the absence of S9 mix. Data demonstrated that E. uchi bark possesses bioactive compounds which exert cytotoxic and genotoxic effects that might be associated with its antitumor potential. Therefore, E. uchi bark aqueous extract consumption needs to be approached with caution in therapeutic applications.
Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias do Colo , Humanos , Camundongos , Animais , Extratos Vegetais/química , Casca de Planta/química , Dano ao DNA , Água , Mutagênicos , Células MCF-7RESUMO
Endopleura uchi, is used for the treatment of inflammatory disease and related to the female reproductive tract. The aim of this study was to evaluate the acute toxicity of the Endopleura uchi stem bark hydroethanolic extract (EEu) in zebrafish, emphasizing the histopathological and biochemical parameters, as well as evaluating the in silico pharmacokinetic and toxicological parameters of the phytochemical/pharmacological marker, bergenin, as their metabolites. The animals were orally treated with EEu at a single dose of 75 mg/kg, 500 mg/kg, 1000 mg/kg and 3000 mg/kg. the oral LD50 of the EEu higher to the dose of 3000 mg/kg. Behavioral, biochemical and histopathological changes were dose dependent. In silico pharmacokinetic predictions for bergenin and its metabolites showed moderate absorption in high human intestinal absorption (HIA) and Caco-2 models, reduced plasma protein binding, by low brain tissue binding and no P-glycoprotein (P-Gp) inhibition. Their metabolism is defined by the CYP450 enzyme, in addition to bergenin inhibition of CYP2C9, CYP3A4 and CYP2C19. In the bergenin and its metabolites in silico toxicity test it have been shown to cause carcinogenicity and a greater involvement of the bergenin with the CYP enzymes in the I and II hepatic and renal metabolism's phases was observed. It is possible to suggest that the histopathological damages are involved with the interaction of this major compound and its metabolites at the level of the cellular-biochemical mechanisms which involve the absorption, metabolization and excretion of these possible prodrug and drug.
RESUMO
Endopleura uchi is a native plant from the Amazon used in popular medicine to treat myomas. A crude polysaccharide (AGb) obtained from E. uchi bark decoction was purified, yielding a type II arabinogalactan (AG) that was characterized by chemical and spectroscopic methods. AG was evaluated for its cytotoxic effects on HeLa cells. AG (5-500 µg/ml) reduced cell viability at 48 and 72 h (approximately 20%) but not in a dose-dependent manner. Cell proliferation was also reduced by AG, with a 25% inhibition (100 µg/ml) at 72 h. The results suggest that the cytotoxicity exhibited by AG does not involve pathways related to the cell cycle.
Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Galactanos/isolamento & purificação , Galactanos/farmacologia , Magnoliopsida/química , Casca de Planta/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HeLa , HumanosRESUMO
The extract obtained in methanol from the fruits pulp of Endopleura uchi was fractionated using conventional chromatographic tecniques to isolate bergenin. In the analysis of the composition of carotenoids was evidenced the predominance of beta-carotene (16.57 mug.g-1). The isomers of beta-carotene: trans-beta-carotene (89.3%), 13-cis-beta-carotene (8%) and 9-cis-beta-carotene (3%) were detected. Considering the importance of the nutritional role of carotenoids and the bioactivity of the bergenina, this study suggested the potential of this fruit as functional food.
O extrato obtido em metanol da polpa de frutos Endopleura uchi foi submetido a fracionamento utilizando-se técnicas cromatográficas convencionais levando ao isolamento de bergenina. Na análise da composição dos carotenóides foi evidenciada a predominância de beta-caroteno (16,57 mig.g-1). Os isômeros do beta-caroteno foram detectados, trans-beta-caroteno (89,3%), 13-cis-beta-caroteno (8%) e 9-cis-beta-caroteno (3%). Considerando a importância do papel nutricional dos carotenóides e a bioatividade do glicosídeo bergenina, esse estudo sugeriu o potencial desse fruto como alimento funcional.
RESUMO
O extrato obtido em metanol da polpa de frutos Endopleura uchi foi submetido a fracionamento utilizando-se técnicas cromatográficas convencionais levando ao isolamento de bergenina. Na análise da composição dos carotenóides foi evidenciada a predominância de beta-caroteno (16,57 mig.g-1). Os isômeros do beta-caroteno foram detectados, trans-beta-caroteno (89,3 por cento), 13-cis-beta-caroteno (8 por cento) e 9-cis-beta-caroteno (3 por cento). Considerando a importância do papel nutricional dos carotenóides e a bioatividade do glicosídeo bergenina, esse estudo sugeriu o potencial desse fruto como alimento funcional.
The extract obtained in methanol from the fruits pulp of Endopleura uchi was fractionated using conventional chromatographic tecniques to isolate bergenin. In the analysis of the composition of carotenoids was evidenced the predominance of beta-carotene (16.57 mug.g-1). The isomers of beta-carotene: trans-beta-carotene (89.3 percent), 13-cis-beta-carotene (8 percent) and 9-cis-beta-carotene (3 percent) were detected. Considering the importance of the nutritional role of carotenoids and the bioactivity of the bergenina, this study suggested the potential of this fruit as functional food.