Search

Graphical abstract, Highlights • E. uchi stem bark hydroethanolic extract in zebrafish. • Evaluating the in silico pharmacokinetic and toxicological parameters. • Behavioral, biochemical and histopathological changes was dose dependent. • In silico bergenin and its metabolites showed high intestinal absorption. • Bergenin inhibited CYP2C9, CYP3A4 and CYP2C19., 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.

The main constituents of the Euterpe oleracea Mart., Arecaceae, fruits (açaí) are anthocyanins. This paper aimed to standardize the extraction process and characterize an anthocyanin-rich dry extract obtained from this fruit. A 23 full factorial design was used. The volumes of ethanol 92% and acetic acid and the extraction time were used as factors. Total solids and anthocyanins content were used as feedback. The dry extract was obtained by freeze-drying. The content of anthocyanins was determined spectrophotometrically. Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimeter, Thermogravimetry, Scanning Electron Microscopy, and Atomic Absorption Spectrometry were used for characterizingthe dry extract. The DPPH method was used for evaluating radical scavenging activity. The extraction conditions were established. The most influent factor was the volume of acetic acid. The dry extract moisture content was equal to 1.39 ± 0.25%, the evaporation residue 97.25 ± 1.28%, total ashes 0.62 ± 0.12%, and the anthocyanin content was 61.75 ± 3.28%. The elemental composition shows the presence of manganese 4.85 ppm, iron 1.62 ppm, zinc 0.05, copper 1.38 ppm, calcium 1.01 ppm, cadmium 0.003 ppm, nickel 0.37 ppm, and lead 0.38 ppm. The dried extract IC50 estimated by the radical scavenging assay with DPPH was 31.25 ± 2.31 ppm. The optimal extraction conditions were: the volume of ethanol 92%: 400 ml; volume of acetic acid: 75 ml; an extraction time: 4 h. Keywords: Açai, Anthocyanins, Antioxidant, Dry extract, Extraction, Factorial design

Purpose: This study aimed to evaluate the hypoglycemic effect, antioxidant, α-glucosidase and lipase inhibitory activity, and the cytotoxicity of the Cassia grandis nanodispersion (CgND). Methods: The hypoglycemic effect was evaluated in alloxan-induced diabetic mice. The particle size, polydispersion index, ζ-potential, and conductivity, as well as the drug-loaded content, were monitored in shelf-live, along a year. The delivery profile was evaluated in simulated intestinal fluids at pH 6.5 and 7.4. The antioxidant effect was evaluated as DPPH and ABTS inhibition. The murine α-glucosidase inhibitory activity and the lipase-inhibitory effect were evaluated in vitro. Cytotoxicity was evaluated by the Alamar blue test. Results: CgND remained stable for a year in shelf conditions. The hypoglycemic effect in a dose of 10 mg/kg was not statistically different from glibenclamide 25 mg/kg. Nanoparticles released 100% of extract in 120 min at pH 6.5 and 7.4. Nanodispersion exhibited a potent α-glucosidase and lipase-inhibitory effect with IC50 of 3.96 and 0.58 µg/mL, respectively. A strong antioxidant activity against DPPH (IC50 0.65 µg/mL) and ABTS (0.48 µg/mL) was also observed. The hypoglycemic effect could occur, at least in part, via antioxidant and α-glucosidase inhibition. CgND is non-cytotoxic in MRC-5 line cell. This nanodispersion is a promising nanotechnological product that could be used in pharmaceuticals for the treatment of Type II diabetes and related complications as obesity. Keywords: Hypoglycemic, Nanodispersion, Cassia grandis, Lipase inhibitory, Alpha-glucosidase, Antioxidant

Increasing efforts have been observed for the development of eco-friendly mosquitocides against arboviruses vectors. The diseases transmitted by some mosquitoes have been of global concern, being huge problems of public health in low-income countries and recent cases in developing countries opened an alert. The control may be performed in the mature form of the mosquitoes or the immature forms, such as larvae and pupae. Growing interest is observed for the nano-based formulations, especially those prepared with natural products. Therefore, this chapter shows recent advances through a revision of the literature and summary of the researches that bring the main nanoformulations and their respective bioactivities against mosquito vectors.

The gastrointestinal tract contains thousands of microorganisms present in the mucosa, derived from several different species, and these microorganisms have a direct relationship with immunity, homeostasis, and certain systemic diseases. The microorganisms present in kefir grains interact with the gastrointestinal and immune systems as well as with the intestinal microbiota. Isoflavones are the most commonly consumed phytoestrogens, with aglycone and glycoside forms. Therefore, in this study, the content of aglycone isoflavones released from kefir associated with soybean germ (KSG) was evaluated in a gastrointestinal digestion model in vitro, and the anxiolytic and antidepressant activity of KSG and the fermentation solution of kefir (FSK) were evaluated in models of anxiety and depression in zebrafish (Danio rerio). KSG was prepared as the 4-day fermentation product of 40 g/L brown sugar, 10 g/L soy germ, and 60 g/L kefir. Isoflavone content was evaluated during the gastric, intestinal, and colon phases in simulated gastrointestinal digestion and analyzed by high-performance liquid chromatography. KSG was administered orally to zebrafish for 30 days, at 200 mg/kg (group G1) and 400 mg/kg (G2), while G3 received 2 μL SFK. The scototaxis test (light–dark) was performed to assess anxiolytic activity, using caffeine (100 mg/kg) as an anxiolytic, buspirone (25 mg/kg) as a positive control, and distilled water as a negative control. To assess antidepressant activity, a new tank dive test was performed, using 1% ethanol as a depressant, fluoxetine (20 mg/kg) as a positive control, and distilled water as a negative control. An increase in the release of isoflavones in the gastric phase and a decrease in the intestinal and colon phases was demonstrated with KSG. Moreover, the behavioral patterns observed in the different experiments demonstrated that KSG and FSK produce anxiolytic and antidepressant effects.

Aedes aegypti (Diptera: Culicidae) is the main vector of some neglected diseases, including dengue. It is very important to develop formulations that increase effectiveness of vector control with low toxicity. Quercetin is a plant-derived flavonoid that modulates the development of some insects. The low water solubility of quercetin impairs the development of water-dispersible commercial products. To circumvent this problem, the preparation of nanoformulations is considered promising. Thus, this study aimed to evaluate the effect of bulk and quercetin nanosuspension against A. aegypti larvae and also to investigate their ecotoxicity. Quercetin nanosuspension was produced by a solvent displacement method followed by solvent evaporation and was maintained in two different temperatures (4 and 25 °C). Its size distribution and zeta potential were monitored along 30 days. The influence of quercetin nanosuspension and bulk-quercetin was investigated at various concentrations against A. aegypti and the green algae Chlorella vulgaris. The quercetin nanosuspension presented higher stability at 4 °C and negative zeta potential values. Quercetin nanosuspension and bulk-quercetin adversely affected the larvae development, especially at the highest concentrations. Larvae mortality was between 44% and 100% (48 h) for quercetin nanosuspension at 100 and 500 ppm, respectively. The bulk-quercetin induced around 50% mortality regardless the concentration used at this same time-period. Absence of emerging mosquitoes from water was observed on the survival larvae of all the treated groups. Quercetin nanosuspension was less toxic than bulk-quercetin against C. vulgaris, especially at higher concentrations. These data indicate that quercetin nanosuspension may represent a potential larvicide for A. aegypti control, once they induced larvae death and inhibited the survival ones to emerge from water. In addition, it did not demonstrated ecotoxicity against a non-target organism, highlighting its better properties, when compared to the bulk-quercetin. Keywords: Culicidae, Ecotoxicity, Larvicide, Nanocarrier, Flavonoid

Guaco is a traditional medicinal plant that was not previously object of studies within this area, despite its great commercial importance and crop production. To our knowledge, few efforts were carried out for a method that simultaneously extract plant material and generate nano-dispersions. Extraction of leaves with surfactant aqueous solutions allowed obtention of nano-dispersions with mean droplet size and polydispersity index below 300 nm and 0.3, respectively. Zeta potential was around – 30 mV. Chemical analysis indicated that guaco chemical marker (coumarin) was extracted. Guaco nano-dispersion was considered effective against cytotoxic effects induced by cyclophosphamide and significantly reduced micronucleated polychromatic erythrocytes frequency. Moreover, it presented improved bioactivity, when compared to guaco ethanolic extract obtained by classical method. Considering the several advantages of simultaneous extraction/nanoformulation methodology, including reducing costs and quickness of nano-dispersion preparation, the present study successfully used a simple, low-energy method and ecofriendly approach. © 2019 Elsevier B.V., Authors would like to thank CNPQ (Rede Amazônica de Pesquisa em Biofármacos – 407768/2013-0) and FAPEAP (Prodetec Araguari – process nº 250.203.035/2013) for the financial support, INCAPER (Instituto Capixaba de Pesquisa, Assistência Técnica e Extensão Rural) for the plant material and FAPES (Fundação de Amparo a Pesquisa do Espírito Santo) for the pos-graduate grant of the mastering student (first author).

The 19-nor-clerodane trans-crotonin (CTN) and the triterpene acetyl aleuritolic acid (AAA), isolated from the stem bark of Croton cajucara Benth (Euphorbiaceae), a traditional medicinal plant from Amazon region of Brazil, as well as the aqueous extract (AE) from its stem bark, were submitted to pharmacological screening for anti-inflammatory and antinociceptive activities in animal models. The oral administration of AAA (50 mg/kg), CTN (50 mg/kg) or AE (300 mg/kg) inhibited the acetic acid-induced writhing in mice. The AE, CTN and AAA had shown significant inhibition of carrageenin-induced edema in rats, in all time intervals measured after the injection of the stimulus, with the greatest inhibition at the first hour for AAA (47.7%) and the second hour for CTN (54.4%). They have also exhibited significant inhibition in the dextran-induced edema 90 minutes after the stimulus: 31.9% for CTN and 28.5% for AAA. In the histamine-induced edema, the inhibition showed by CTN and AAA were 43.2% and 40.5%, respectively, 90 minutes after the injection of stimulus. This study extends and supports the popular medicine and folkloric uses of Croton cajucara in the Amazon region of Brazil. O 19-nor-clerodano trans-crotonina (CTN) e o triterpeno ácido acetil aleuritólico (AAA), isolados das cascas do caule de Croton cajucara Benth (Euphorbiaceae), uma planta tradicional da Região Amazônica do Brasil, bem como o extrato aquoso (EA) das cascas do caule deste Croton, foram submetidos a experimentos farmacológicos utilizando animais, para avaliação das atividades anti-inflamatória e antinociceptiva. A administração oral de AAA (50 mg/kg), CTN (50 mg/kg) ou AE (300 mg/kg) inibiram as contorções em ratos, induzidas por ácido acético. Os terpenóides AAA e CTN, bem como o extrato polar EA, inibiram significativamente o edema de pata em ratos, induzido por carragenina. As inibições foram observadas em todos os intervalos de medições, tendo sido evidenciado melhores inibições para os terpenóides AAA (47,7%, após a primeira hora) e CTN (54,4%, após a segunda hora). Evidenciou-se ainda, após 90 minutos do estímulo, significante inibição no edema induzido por dextrana (31,9% para CTN e 28,5% para AAA) e por histamina (43,2% para CTN e 40,5% para AAA). Estes resultados confirmam o uso popular de Croton cajucara na região Amazônica do Brasil, no combate a inflamações.

Diabetes mellitus is a syndrome that reaches more than 382 million people worldwide. It interferes with the metabolism of carbohydrates, causing chronic hyperglycemia. The objective of this study was to evaluate the effect of the Copaifera duckei, Dwyer, Fabaceae, oleoresin on streptozotocin-induced (STZ) diabetic rats. This study was based on the induction of diabetes mellitus by streptozotocin (55 mg/kg, i.p.) in Wistar rats and treated with doses of C. duckei oleoresin (250 and 500 mg/kg, p.o.). Subsequently, the clinical, biochemical and histopathological of the pancreas parameters were evaluated. Gas chromatographic analysis indicated that β-bisabolene (22.29%), β-caryophyllene (21.25%) and α-farnesene (15.58%) sesquiterpenes were the major components of the C. duckei oleoresin. In streptozotocin-induced diabetes mellitus, it was possible to observe that the C. duckei oleoresin treatment had a significant effect (p

Copaiba (Copaifera duckei Dwyer, Fabaceae) oleoresin is an important Amazonian raw material. Despite its insecticidal potential, poor water solubility remains a challenge for the development of effective and viable products. Nanotechnology has emerged as a promising area to solve this problem, especially oil-in-water nanoemulsions. On this context, the aim of the present study was to develop oil-in-water nanoemulsions using copaiba oleoresin dispersed through a high internal phase; and evaluate its potential insecticidal action against Aedes aegypti larvae. Overall, 31 formulations were prepared, ranging from 11.5 ± 0.2 to 257.3 ± 4.1 nm after one day of manipulation. Some of them reached small mean droplet sizes (< 200 nm) and allowed achievement of a nanoemulsion region. The formulation consisted of 5% (w/w) of copaiba oil, 5% (w/w) of surfactant and 90% (w/w) of water, which presented mean droplet size of 145.2 ±0.9 nm and polidispersity of 0.378 ± 0.009 after one day of manipulation, and these were evaluated for larvicidal potential. According to mortality level (250 ppm - 93.3 after 48 h), this nanoemulsion was classified as a promising insecticidal agent against Aedes aegypti larvae. The present study allowed the development of low-cost ecofriendly green natural-based nanoformulations with potential larvicidal activity, using a nanobiotechnology approach. Keywords: Aedes aegypti Copaiba Larvicidal Nanoemulsion Oleoresin

Diabetes mellitus is a chronic and severe metabolic dysfunction, it's slow and progressive evolution interferes directly in the metabolism of carbohydrates, fats and proteins, causing hyperglycemia, glycosuria, polydipsia, hyperlipidaemia, among others. The aim of this study was to evaluate the antidiabetic effect of hydroethanolic extract and granulated of Calophyllum brasiliense Cambess., Clusiaceae, species in diabetic rats as well as it's biochemical parameters. The results demonstrated that both the pharmaceutical forms, hydroethanolic extract and granulated, were able to reduce significantly (p