Genotoxic and antiproliferative properties of Endopleura uchi bark aqueous extract.

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.

Bacaba, Pracaxi and Uxi Oils for Therapeutic Purposes: A Scoping Review.

Fruits such as bacaba (Oenocarpus bacaba Mart), pracaxi (Pentaclethra macroloba Kuntze) and uxi (Endopleura uchi (Huber) Cuatrec), from the Amazon rainforest, are potentially interesting for studies of natural products. The current article aims at mapping and characterizing studies on the bacaba, pracaxi and uxi species. This review reports the main bioactive compounds identified in these species and discusses their therapeutic potential. Searches were performed in MEDLINE (Via Pubmed) and Web of Science. Thirty-one studies that described or evaluated the development of formulations aimed at the therapeutic use of the species were included. The findings suggest that species have the potential for the development of pharmaceutical formulations due to their therapeutic properties. However, further studies are required to assess safety and efficacy of these products. Therefore, it is suggested that new research studies propose strategies so that technological development is based on awareness and preservation of the biome.

Endopleura uchi - A review about its nutritional compounds, biological activities and production market.

Endopleura uchi (Huber) Cuatrec, known as uxi, is a native plant from the Amazon region, which has been used by locals for some pathology treatments. This review aimed to find the main uxi studies carried out in scientific literature. This compilation includes the biological activities that have been proven, parts of the plant that were exploited, as well as its nutritional properties. Uxi fruit has compounds, such as vitamins A and E, minerals, bioactive phenolic and organic acids, along with anti-inflammatory, antioxidant, antibacterial, antidiabetic, and anti-cholesterol actions. Some E. uchi extract activities have been reported, such as: α-glucosidase and cyclooxygenases (COX1/COX2) inhibitions, in addition to anti-bactericidal properties. The isocoumarin compound, bergenin is responsible for many of the reported biological activities of this species. E. uchi can be used for manufacturing products in food, pharmaceutical, and cosmetic industries, demonstrating its worth, regional economic growth, along the potential to dominate the worldwide market.

Hydroethanolic extract from Endopleura uchi (Huber) Cuatrecasas and its marker bergenin: Toxicological and pharmacokinetic studies in silico and in vivo on zebrafish.

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.

Endopleura uchi (Huber) Cuatrec.: A medicinal plant for gynecological treatments - A reproductive toxicity assessment in zebrafish (Danio rerio).

ETHNOPHARMACOLOGICAL RELEVANCE: Endopleura uchi (Huber) Cuatrec is a plant species from the Brazilian Amazon. The barks of this tree are used in folk medicine - mainly as a decoction - for dyslipidemia, uterine infection, fibroids, polycystic ovary, menstrual disorders, as a contraceptive and abortive agent, among others. However, the data available about its developmental toxicity are still insufficient. AIM OF THE STUDY: This study aimed to evaluate the reproductive toxicity and teratogenic effects in embryos from zebrafish treated with the hydroethanolic extract from the barks of Endopleura uchi (EEu). MATERIALS AND METHODS: Both sexes of zebrafish (Danio rerio) were treated with EEu either through immersion (1.2, 2.5, and 5 mg/L) or orally (75, 200, and 500 mg/kg) over 21 consecutive days. Next, we assessed their fertility and gonads' histopathology; in their embryos were assessed teratogenesis, lethalities, and heart rate during daily observations (24, 48, 72, and 96 hpf). RESULTS: The phytochemical analysis of EEu through HPLC/MS shows bergenin as the major compounds. After 21 days of treatment were detected minor histopathological changes in parental fishes, such as atretic oocytes, interstitial fibrosis, and decreased the percentage of early vitellogenic oocytes, but without impairing the reproduction of treated animals. However, in the embryos was observed significantly increased frequency of malformation in all the groups treated through immersion, and in the group treated orally with the highest concentration (500 mg/kg). CONCLUSION: Based on the results, EEu caused no adverse effects in the progenitors on both treatments (immersion and oral). However, it was observed that the concentrations 1.2, 2.5, and 5 mg/L (immersion), and the dose 500 mg/kg (oral) caused malformations in the offspring (F1 generation). These results emphasize the need for attention when using preparations from E. uchi, mainly for pregnant women. Further studies are needed to compare its effects with the extract's primary compound (bergenin).

Bark Extract of the Amazonian Tree Endopleura uchi (Humiriaceae) Extends Lifespan and Enhances Stress Resistance in Caenorhabditis elegans.

Endopleura uchi (Huber) Cuatrec (Humiriaceae), known as uxi or uxi-amarelo in Brazil, is an endemic tree of the Amazon forest. In traditional medicine, its stem bark is used to treat a variety of health disorders, including cancer, diabetes, arthritis, uterine inflammation, and gynecological infections. According to HPLC analysis, the main constituent of the bark extract is the polyphenol bergenin. In the current study, we demonstrate by in vitro and in vivo experiments the antioxidant potential of a water extract from the stem bark of E. uchi. When tested in the model organism Caenorhabditis elegans, the extract enhanced stress resistance via the DAF-16/FOXO pathway. Additionally, the extract promoted an increase in the lifespan of the worms independent from caloric restriction. It also attenuated the age-related muscle function decline and formation of polyQ40 plaques, as a model for Huntington's disease. Thus, these data support anti-aging and anti-oxidant properties of E. uchi, which has not yet been described. More studies are needed to assess the real benefits of E. uchi bark for human health and its toxicological profile.

Phenolic profile and biological potential of Endopleura uchi extracts.

OBJECTIVE: To improve the knowledge on the metabolite composition of Endopleura uchi bark, concerning phenolic compounds, and to evaluate some of its biological capacities for further possible exploitation in food and pharmaceutical industries associated to their health-promoting qualities. METHODS: Two different extracts (infusion and hydroethanolic) were studied concerning phenolic composition and biological potential. RESULTS: Five compounds were determined by HPLC-DAD, being bergenin the major one. In general way, infusion presents a greater richness in these metabolites. The antioxidant, acetylcholinesterase, butyrylcholinesterase, α-glucosidase and antibacterial activity were checked by in vitro assays. A dose-dependent response was noticed against DPPH, superoxide and nitric oxide radicals, acetylcholinesterase, butyrylcholinesterase and against α-glucosidase inhibitory assay. Antibacterial capacity of both extracts was investigated against Gram-positive and Gram-negative bacteria, being more effective against the first one. The concentrations of infusion extract tested here revealed that is non-toxic for intestinal (Caco-2) cells line. CONCLUSIONS: The results suggest that the extracts of Endopleura uchi may be interesting for incorporating in pharmaceutical preparations for human health, since it can suppress hyperglycaemia and inhibit cholinesteases, and or as food additive due to its antiradical and antibacterial activities.

Phenolic profile and biological potential of Endopleura uchi extracts

OBJECTIVE@#To improve the knowledge on the metabolite composition of Endopleura uchi bark, concerning phenolic compounds, and to evaluate some of its biological capacities for further possible exploitation in food and pharmaceutical industries associated to their health-promoting qualities.@*METHODS@#Two different extracts (infusion and hydroethanolic) were studied concerning phenolic composition and biological potential.@*RESULTS@#Five compounds were determined by HPLC-DAD, being bergenin the major one. In general way, infusion presents a greater richness in these metabolites. The antioxidant, acetylcholinesterase, butyrylcholinesterase, α-glucosidase and antibacterial activity were checked by in vitro assays. A dose-dependent response was noticed against DPPH, superoxide and nitric oxide radicals, acetylcholinesterase, butyrylcholinesterase and against α-glucosidase inhibitory assay. Antibacterial capacity of both extracts was investigated against Gram-positive and Gram-negative bacteria, being more effective against the first one. The concentrations of infusion extract tested here revealed that is non-toxic for intestinal (Caco-2) cells line.@*CONCLUSIONS@#The results suggest that the extracts of Endopleura uchi may be interesting for incorporating in pharmaceutical preparations for human health, since it can suppress hyperglycaemia and inhibit cholinesteases, and or as food additive due to its antiradical and antibacterial activities.

Phenolic profile and biological potential of Endopleura uchi extracts

Objective: To improve the knowledge on the metabolite composition of Endopleura uchi bark, concerning phenolic compounds, and to evaluate some of its biological capacities for further possible exploitation in food and pharmaceutical industries associated to their health-promoting qualities. Methods: Two different extracts (infusion and hydroethanolic) were studied concerning phenolic composition and biological potential. Results: Five compounds were determined by HPLC-DAD, being bergenin the major one. In general way, infusion presents a greater richness in these metabolites. The antioxidant, acetylcholinesterase, butyrylcholinesterase, α-glucosidase and antibacterial activity were checked by in vitro assays. A dose-dependent response was noticed against DPPH, superoxide and nitric oxide radicals, acetylcholinesterase, butyrylcholinesterase and against α-glucosidase inhibitory assay. Antibacterial capacity of both extracts was investigated against Gram-positive and Gram-negative bacteria, being more effective against the first one. The concentrations of infusion extract tested here revealed that is non-toxic for intestinal (Caco-2) cells line. Conclusions: The results suggest that the extracts of Endopleura uchi may be interesting for incorporating in pharmaceutical preparations for human health, since it can suppress hyperglycaemia and inhibit cholinesteases, and or as food additive due to its antiradical and antibacterial activities.

Isolation of an arabinogalactan from Endopleura uchi bark decoction and its effect on HeLa cells.

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.

Antimicrobial, cytotoxic and antioxidant activities and determination of the total tannin content of bark extracts Endopleura uchi.

Endopleura uchi is a typical Amazonian tree and its bark is popularly employed in the preparation of teas against myomas, arthritis, influenza, diarrhea and cancer. In this study, the antioxidant activity, cytotoxicity and antimicrobial activity of five different extracts of the bark, selected by their total tannin content, were assessed. The potential antioxidant activity of the extracts was determined by 2.2-diphenyl-1-picrylhydrazyl radical scavenging assay and the values found were very similar among the extracts and to the standards antioxidants used in the tests. Cytotoxicity analysis in mammalian cells indicated that all the tested extracts exhibited IC(50) values higher than the highest concentration used, showing that they do not present a risk when consumed under these conditions. Extract tested against five bacterial strains and one yeast strain did not show satisfactory growth inhibitory activity, and even the extracts that showed some antimicrobial activity were not effective at any dilution to determine the minimum inhibitory concentration. The results may serve as a reference for subsequent works, since such reference values described in the literature for the bark of E. uchi.

Identificação de bergenina e carotenóides no fruto de uchi (Endopleura uchi, Humiriaceae) / Identification of bergenin and carotenoids in the uchi (Endopleura uchi, Humiriaceae) fruit

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.