Lecithin-based nanocapsule loading sucupira (Pterodon emarginatus) oil effects in experimental mucositis.

Intestinal mucositis (IM) is a frequent adverse effect in anticancer therapy without standard treatment. The oil obtained from sucupira (Pterodon emarginatus) has anti-inflammatory properties, and the soybean lecithin reduces the intestinal toxicity of several xenobiotics. However, their water insolubility impairs the in vivo application. For this reason, we evaluated if the nanoencapsulation of sucupira oil (SO) in lecithin-based nanocapsules (SO-NC) could be a therapeutically effective system for the treatment of IM in murine cisplatin (CDDP)-induced intestinal mucositis model. SO was analyzed by LC-HRMS/MS and HPLC. SO-NC was prepared by nanoprecipitation and characterized using DLS, HPLC, and AFM. Mice body weight and food consumption were assessed daily during experimental mucositis induced by CDDP. The animals were euthanized, and intestinal permeability, inflammatory mediators, and intestinal histology were performed. SO-NC demonstrated adequate characteristics for oral administration as size under 300 nm, IP < 0.3, high EE, and spherical shape. In vitro cytotoxicity performed against RAW 264.7 cell lines resulted in cell viability above 80 % confirming the non-cytotoxic profile of SO (IC50 268 µg/mL) and SO-NC (IC50 118.5 µg/mL) up to 117.2 µg/mL. The untreated mice showed intestinal toxicity after i.p. of CDDP, principally weight loss, increased intestinal permeability, and MPO and TNF-α levels. Surprisingly, the administration of SO to CDDP-mucositis animals did not circumvent the CDDP effects and increased intestinal permeability. However, SO-NC proved efficient in mitigating the experimental intestinal mucositis by improving intestinal epithelium architecture, reducing intestinal permeability, and improving the MPO levels. In conclusion, SO-NC can positively impact intestinal mucositis by promoting mucosal recovery. This is a promising strategy for developing a new treatment for intestinal mucositis.

Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran.

Kefiran is a polysaccharide present in kefir grains that have been widely explored due to its potential health benefits. The objective of this work was to characterize and quantify the components present in the ethanolic extract of milk kefir grains; to study its pharmacokinetic and toxicological properties in silico and evaluate the acute toxicity of the kefiran in zebrafish. The prediction of pharmacokinetic properties was performed by QikProp software. In silico toxicity assessment was performed using the DEREK (deductive estimate of risk from existing knowledge) software. In the chromatographic, kefiran was identified as the major component. Results showed that the kefiran had low human oral absorption and intestinal absorption its due poor solubility profile; low logP value, indicating its lipophilicity and the low MDCK and Caco-2 cells permability, and unable to cross the blood-brain barrier. Kefiran did not present any structural warning for in silico toxicity. In zebrafish, the dose of 2,000 mg/kg of kefiran produced nonsignificant alterations in the analyzed organs. It can be said then that kefiran has an acceptable degree of safety for use in the development of drugs or functional foods. Further research such as in vivo testing to confirm its pharmacological potential is currently underway.

Molecular Docking, Physicochemical Properties, Pharmacokinetics and Toxicity of Flavonoids Present in Euterpe oleracea Martius.

BACKGROUND: Euterpe oleracea Martius, popularly known as açaí, is a fruit rich in α- tocopherols, fibers, lipids, mineral ions, and polyphenols. It is believed that the high content of polyphenols, especially flavonoids, provides several health-promoting effects to the açaí fruit, including anti-inflammatory, immunomodulatory, antinociceptive and antioxidant properties. Most of the flavonoids are antioxidant molecules of plant origin that act as a trap for free radicals, reacting and neutralizing them, thus offering perspectives in preventing oxidative damage. OBJECTIVE: In this study, we aim to perform an in silico evaluation of flavonoids present in the pulp and the oil of Euterpe oleracea Martius, evaluating their potential to serve as antioxidant agents. METHODS: Firstly, we selected 16 flavonoids present in Euterpe oleracea Martius pulp and oil, and then their physicochemical properties were analyzed concerning the Lipinski's Rule of Five. Moreover, we evaluated their pharmacokinetic properties using the QikProp module of the Schrödinger software as well as their toxicity profile, using the DEREK software. Docking simulations, using the GOLD 4.1 software, as well as pharmacophoric hypotheses calculation of molecules were also performed. RESULTS: Flavonoids present in the açaí pulp including catechin, epicatechin, luteolin, chrisoeriol, taxifolin, apigenin, dihydrokaempferol, isovitexin, and vitexin presented good oral bioavailability. Regarding the pharmacokinetic properties, the compounds catechin, epicatechin, isovitexin, luteolin, chrisoeriol, taxifolin, and isorhamnetin rutinoside presented the best results, besides high human oral absorption. Regarding the prediction of toxicological properties, compounds isorhamnetin rutinoside and rutin presented mutagenicity for hydroxynaphthalene or derivate, and regarding the docking simulations, all the compounds investigated in this study presented key interactions with the corresponding targets. CONCLUSION: The flavonoids catechin, chrysoeriol, and taxifolin presented the best results according to the evaluation conducted in this study. These computational results can be used as a theoretical basis for future studies concerning the development of drug candidates, as well as to enlighten biological tests in vitro and in vivo, which can contribute to the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.

Nano-emulsification Enhances the Larvicidal Potential of the Essential Oil of Siparuna guianensis (Laurales: Siparunaceae) Against Aedes (Stegomyia) aegypti (Diptera: Culicidae).

Siparuna guianensis (Laurales: Siparunaceae) has a terpene-rich essential oil with great potential for larvicides. The poor water miscibility of their compounds makes nano-emulsions of great interest for novel bioactive systems, including for control of Aedes aegypti (Diptera: Culicidae). This species is adapted to urban environments with important role in the epidemiology of some arboviruses such as dengue, chikungunya fever, zika, and urban yellow fever. The aim of the present study was to evaluate the feasibility of nano-emulsification to affect Ae. aegypti larvae. An optimal system was achieved by using a nonionic single surfactant, highlighted by its satisfactory size distribution profile. Moreover, improved larvicidal activity in comparison to bulk essential oil can be observed for the nano-emulsions. The estimated LC50 and LC90 values after 24 h of treatment of larvae with the essential oil were, respectively, 86.5232 and 134.814 µg/ml, while the estimated LC50 and LC90 value after treatment with the nano-emulsion were 24.7572 and 75.2452 µg/ml, respectively. The utilization of a simple technique to produce a fine nano-emulsion opens perspective for further integrative practices of mosquito control and giving value to this Amazon plant species may encourage its sustainable use and contribute to conservation policies.

Antioxidant Effect of Flavonoids Present in Euterpe oleracea Martius and Neurodegenerative Diseases: A Literature Review.

INTRODUCTION: Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins. METHODS: In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí. RESULTS: Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function. CONCLUSION: This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.

Nanosuspension of quercetin: preparation, characterization and effects against Aedes aegypti larvae

Abstract 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 ºC). 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 ºC 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.

Leaves of Spondias mombin L. a traditional anxiolytic and antidepressant: Pharmacological evaluation on zebrafish (Danio rerio).

ETHNOBOTANICAL RELEVANCE: Spondias mombin L. is a plant dispersed throughout the tropical regions of South America, Africa, and Asia, being found mainly in the North and Northeast of Brazil, where the leaves are used in preparations for neuropsychiatric disorders. Therefore, it is of great importance to carry out studies in different pharmacological models that can prove the traditional use of this plant species. MATERIALS AND METHODS: the hydroethanolic extract from S. mombin leaves (HELSm) was evaluated by oral administration (25 mg/kg) and by immersion (25 mg/l) in scototaxis test in zebrafish (Danio rerio). For this study, caffeine (100 mg/kg) and buspirone (25 mg/kg) were used as standard drugs. The antidepressant action of the HELSm was evaluated assessed in the novel tank diving test (NTDT). In this study, a group with 1% ethanol, one with unpredictable chronic mild stress (UCMS), and another with developmental, social isolation (DSI) were used as induction groups for depression-like behavior and fluoxetine (20 mg/kg) as a drug pattern. RESULTS: by the HPLC-UV fingerprint analysis, the HELSm presented several derivatives of polyphenolic compounds and flavonoids and identified ellagic acid and isoquercitrin, and by the gas-chromatographic, the majority of the identified compounds were fatty acids, esters, and alcohols. By immersion, the LC50 was 49.86 mg/l and by oral via the LD50 in 48 h, was 4.515 g/kg in zebrafish. For all spatiotemporal and behavioral variables (time spent, white compartment, latency, toggle, erratic swimming, freezing duration, thigmotaxis, and risk assessment), the treatment with HELSm produced a similar effect to buspirone and was significant when compared to the caffeine and control group (p < 0.01, Tukey-Kramer test). For all spatiotemporal and behavioral variables evaluated (time spent at the top of the apparatus, crossed quadrants, erratic swimming, and duration of freezing), treatment with HELSm produced a change in the depression-like behavior in the groups tested, with a similar effect to fluoxetine, both with a significant difference when compared to the control groups (p < 0.01). CONCLUSIONS: Our results suggest that the acute administration of the HELSm in the scototaxis and NTDT tests in a zebrafish model (Danio rerio) produced anxiolytic and antidepressant effects, devoid of hypnotic and sedative actions by immersion, and this action was improved when administered by oral via. Possibly, the presence of isoquercitrin in the leaves of Spondias mombin participates in the anxiolytic and antidepressant effects.

Anti-inflammatory and antialgic actions of a nanoemulsion of Rosmarinus officinalis L. essential oil and a molecular docking study of its major chemical constituents.

We evaluate the anti-inflammatory and antialgic potency of a nanoemulsion (NEORO) containing the essential oil of Rosmarinus officinalis L. (EORO), which is composed primarily of limonene, camphor and 1,8-cineole. The EORO and NEORO were administered orally 30 min prior to starting the experiments. In a test of rat paw oedema induced by carrageenan, NEORO was effective in doses of 498 µg/kg, and it inhibited 46% of the maximum peak of the oedema; in a dose of 300 mg/kg, EORO inhibited 50% of the maximum peak of the oedema. In an acetic acid-induced writhing test, NEORO yielded a dose-dependent effect, and a dose of 830 µg/kg inhibited 84% of the algesic process; a dose of 100 mg/kg of EORO inhibited 55%. In an assay for H2S production in rat stomachs, a dose of 498 µg/kg of NEORO inhibited H2S production in all of the measurement phases, and a dose of 100 mg/kg EORO inhibited 60% and influenced the effect of the ethanol significantly, reducing the production of H2S. We suggest that NEORO potentiated the effect of EORO, demonstrating effectiveness in doses 600 times lower than those applied with EORO. Among the major compounds of EORO, the camphor molecule exhibited the largest number of interactions with the therapeutic targets related to the inflammatory process, suggesting that it is responsible for EORO's anti-inflammatory and antialgic effects. This work paves the way for future investigations related to the therapeutic role of NEORO in the inflammation process.

A new tropane alkaloid from the leaves of Erythroxylum subsessile isolated by pH-zone-refining counter-current chromatography.

Tropane alkaloids are bioactive metabolites with great importance in the pharmaceutical industry and the most important class of natural products found in the Erythroxylum genus. However, these compounds are usually separated by traditional chromatographic techniques, in which the sample is progressively purified in multiple chromatographic steps, resulting in a time- and solvent-consuming procedure. In this work we present the isolation of a novel alkaloid, 6ß,7ß-dibenzoyloxytropan-3α-ol, together with the two known 3α-benzoyloxynortropan-6ß-ol and 3α,6ß-dibenzoyloxytropane alkaloids, directly from the crude alkaloid fraction from the leaves of Erythroxylum subsessile, by using a single run pH-zone-refining counter-current chromatography method. The ethyl acetate/water (1:1, v/v) biphasic solvent system with triethylamine and HCl as retention and eluter agents, respectively, was used to isolate tropane alkaloids for the first time. The structures of the isolated alkaloids were elucidated by spectroscopic methods.