Search

Randia ferox is a Brazilian native species used in folk medicine. Scientific information regarding the toxicology and phytochemistry of this plant remains unclear. We aimed to produce a R. ferox extract, identify its chemical matrix, and evaluate its safety profile. The extract chemical composition was accessed through UHPLC-MS/MS. Mononuclear cells, erythrocytes, fibroblasts, macrophages, and kidney cells were subjected to extract concentration-response curve testing. The cellular viability, proliferation, dsDNA release, reactive oxygen species (ROS), nitric oxide (NO), hemolysis, and DNA damage were determined. Ten molecules were found in the extract matrix. Most of the tested concentrations can be considered safe. Cellular viability, proliferation, dsDNA release, and NO remained at similar levels to the control. The extract increased ROS in macrophages. None of the tested concentrations induced DNA damage or hemolysis. The data suggest R. ferox extract contains several bioactive molecules and has a safety profile in vitro.

Ethnopharmacological relevance: Tucumã (Astrocaryum vulgare)is a fruit native to the Amazon region. Extracts from the peel and pulp are thought of as promising treatments for bacterial infections. The primary constituents of Tucumã oil and butter possess unsaturated carbon chains that are susceptible to oxidation by light or heat. The oils have high volatility and low aqueous solubility that limits their use without a vehicle. Nanotechnology refers to techniques to solve these problems. Nanostructured lipid carriers (NLC), for example, protect fixed oils degradation by heat or light, as well as from oxidation and evaporation, ensuring greater stability and function, thereby prolonging the useful life of the final product. Study objectives: The objective of this study was to evaluate the hemolytic, cytotoxic, antimicrobial and antibiofilm properties of an NLC containing Tucumã butter and oil soasto improve the solubility and photosensitivity of the compounds, generating better pharmacological efficacy. Materials and methods: The NLC was assessed for stability for 60 days. The cytotoxicity of nanoparticles in peripheral blood mononucleated cells was determined in culture using assays for cell viability, DNA damage, oxidative metabolism and damage to human erythrocytes. Antimicrobial activity was determined using the broth microdilution technique and antibiofilm activity according to standardized protocols. Results: The Tucumã NLC remained stable throughout the evaluated period, with pH between 5.22–5.35, monodisperse distribution (PDI

The objective of this work was to produce and characterise nanoemulsions containing tucumã extract and to evaluate the performance of the nanostructure and the free compound regarding antitumor activity, cytotoxicity, and oxidative metabolism in NB4/APL cells. The nanoemulsions showed adequate physicochemical characteristics (average size approx. 200 nm, polydispersity index less than 0.3, negative zeta potential and acid pH) maintained stable up to 90 days of storage in refrigeration condition. The nanoformulations did not present protein corona formation. Blank nanoemulsion treatments showed moderate toxicity. Furthermore, the nanoemulsion loaded with extract showed better antileukemic results than the free extract. However, nanoemulsions can be promising carriers of natural compounds, emphasising their biological properties and constituting alternatives in treating diseases.

Ruellia angustiflora (Acanthaceae) is known as flower-of-fire, and its leaves are traditionally employed to promote wound healing. This study was aimed at extracting and characterizing the chemical constituents of the extracts of R. angustiflora obtained by ultrasound-assisted and supercritical fluid extractions, and subsequently investigate their antioxidant potential and cyto-genotoxicity. The extract obtained by ultrasound (UAE-EtOH) was characterized by ultraperformance liquid chromatography-mass spectrometer (UPLC-MS), and the extract obtained via supercritical fluid (SFE-CO2) by gas chromatograph-mass spectrometer (GC-MS). The antioxidant potential was verified by the antiradical activity against the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), and the cyto-genotoxicity evaluation to test cell viability and DNA damage was performed in peripheral blood mononuclear cells (PBMC) cultures. The SFE-CO2 extract presented some fatty acids, triterpenes, tetraterpenes, tocopherols and phytosterols. The UAE-EtOH extract contained phenolic acids and flavonoids, and showed the highest antioxidant capacity. Neither extract was genotoxic or cytotoxic at the tested concentrations.

Hesperozygis ringens is a plant of the Lamiaceae family which is restricted to the Southern region of Brazil. It is popularly used as an insecticide, but knowledge on it is very scarce. This study aimed to determine the chemical markers of H. ringens extracts obtained via ultrasound-assisted (UAE-EtOH) and supercritical fluid (SFE-CO2) extractions. UAE-EtOH and SFE-CO2 extracts were characterised by UPLC-MS and GC-MS, respectively. Both products had their antioxidant activity, cytotoxicity and genotoxicity evaluated. Twelve compounds were found in the UAE-EtOH extract, including phenolic acids and flavonoids; the SFE-CO2 extract contained terpenes and phytosterols. The UAE-EtOH extract showed a greater antioxidant activity. Neither extract presented cytotoxicity or genotoxicity against human mononuclear blood cells.

Microalgae are eukaryotic and unicellular microorganisms of simple structure, colonial that need for their growth and reproduction, light, water, carbon dioxide and inorganic nutrients. Demonstrate commercial interest due to a biomass rich in bioactive substances, such as pigments, lipids, polyunsaturated fatty acids, carbohydrates, proteins, and vitamins. Among these substances, Chlorella microalgae oil contains lipids with a wide range of interesting properties. In this context, the present review aims to demonstrate the potential and applications of microalgae, mainly of the Chlorella species, as well as the methods and conditions of cultivation, the chemical composition, and its relationship with nanotechnology. The data for this review were obtained from a search in the main databases such as Scielo, Scopus and Science Direct, without restriction to the period of publication, using following descriptors: microalgae, Chlorella, biomass, oil, application, nanotechnology and their combinations. These microorganisms, as they are easy to cultivate and rapidly proliferate, are gaining ground in the area of new technologies involving species of the Chlorella type, which has several applications, including in the nutraceutical and cosmetics area, guaranteeing products with quality, efficacy and biodegradable assets.

With the growing need to develop effective and sustainable therapeutic alternatives, research has been focusing on the association of products of natural origin with nanotechnology, which besides enhancing the action, acts to protect the constituents from degradation. A fruit highlighted in research today is Astrocaryum vulgare (Tucuma), as well as natural fixed oils extracted from seeds, such as grape seed oil and microalgae biomass. The present study aimed to evaluate the parameters of pharmacological safety and in vitro hemocompatibility of lipid nanocarriers (CLN) from the association of tucuma butter with two oils (grape seed and microalgae). Hemocompatibility rates were assessed by analyzing hemolytic activity, in addition to clotting time and clot retraction, whereas pharmacological safety analyzed parameters such as cell viability, DNA damage, dichloride and nitric oxide production. The nanocarriers produced through the association of butter with oils showed a satisfactory pharmacological safety and hemocompatibility profile.

The Amazon region has a wide variety of native palm trees that have fruits and oilseeds. Among these palm trees, Para tucuma (Astrocaryum vulgare) stands out, which provides the tucuma fruit from which its oil is extracted, which has anti-inflammatory, antioxidant, healing and antibacterial properties, among others. However, oils, like that of tucuma, are sensitive to thermal degradation, as well as oxidative reactions, which can reduce their pharmacological effectiveness. In this way, nanotechnology can be a tool to preserve the pharmacological properties of essential oils and increase their therapeutic effectiveness. Therefore, this study aims to develop a nanostructured lipid carrier (NLC) containing tucuma butter and oil, to analyze its in vitro properties of anti-inflammatory and healing activity. For that, tests of anti-inflammatory activity and healing activity were performed by the Scratch test in vitro. The results of the tests demonstrated that the majority of the NLC concentrations showed anti and pro-inflammatory and healing activity.

In this work was to develop an inedited nanocapsule with tucumã oil (Astrocaryum vulgare). The oil presents of phytosterols (squalene and β-sitosterol), all-trans-beta-carotene, acids oleic and palmitic. Antioxidant activity showed a good performance in DPPH and ABTS assays. The nanocapsules were prepared and demonstrated in their characterization particle size (206 ± 0.69 nm). The cytogenotoxicity evaluation was performed using the MTT, dichlorofluorescein, nitric oxide and dsDNA PicoGreen® assays. Antitumor efficacy assays in MCF-7 cells demonstrated that free oil and tucumã nanocapsules had IC50 of 130 and 50 μg/mL, respectively. Thus, previous studies of toxicity are relevant, as they generate future subsidies, aiming at the potential application of nanostructures and in addition, the promising effect of NCs of tucumã oil on the antiproliferative effect in breast adenocarcinoma cells was evidenced.

Hospital Infection is a major health problem and affects around 1.5 million people annually around the world. The Amazon region has a wide diversity of native palm trees that have fruits and oilseeds. Astrocaryum vulgare, commonly known as Tucumã in Brazil, belongs to the family Arecaceae. This palm has orange, fleshy, single-egg-shaped fruits that are used for therapeutic purposes in diseases of the eyes and skin due to the high content of carotenoids, oil is used in cooking, health treatment and massage. This study evaluated the antimicrobial activity of the Tucumã oil against 18 microorganisms. The antimicrobial activity of Tucumã was measured through the determination of the Minimum Inhibitory Concentration (MIC), as well as the determination of the Minimum Microbicidal Concentration (CMM) aiming to contribute to the discovery of new antimicrobials against pathogenic microorganisms’ human health and may contribute to the treatment of nosocomial infections. The results showed that the oil of Tucumã presented antimicrobial activity against five important bacteria, four Gram - positive bacteria (Enterococcus faecalis, Enterococcus faecium, Staphylococcus epidermidis and Streptococcus agalactiae) and one Gram - negative (Acinetobacter baumannii).

The cubiu (Solanum sessiliflorum) is a tropical fruit native to the Amazon region and widely used in medicine and cosmetics, despite the lack of research regarding the actual safety and effectiveness of its use for these purposes. This study aimed to evaluated the phytochemical characterization, pharmacological properties (skin wound healing, antimicrobial and anti-inflammatory properties), and toxicity of cubiu extract. The cubiu antimicrobial capacity was determined against strains of Aeromonas caviae, Pseudomonas aeruginosa, and Sphingomonas paucimobilis. Additionally, cubiu toxicity (hemolysis, coagulation, cell viability, and genotoxicity tests), antioxidant activity (reactive oxygen species total levels), scratch assay (in vitro skin wound healing), and anti-inflammatory activity against phytohemagglutinin and in the scratch assay (Interleukin 1, interleukin 6, interleukin 10, tumor necrosis factor-alpha, and interferon-gamma levels), were evaluated. Human fibroblast cells were used to evaluate skin wound healing, and human peripheral blood mononuclear cells were used for the other assessments. Our findings showed that the cubiu extract is rich in phenolic compounds, the major compound being 5-caffeoylquinic acid. In addition, was effective against the three bacterial strains tested and inhibited and destroyed the biofilm formed by Pseudomonas aeruginosa. The cubiu extract also was no toxicity, maintained the hemocompatibility parameters in the biological range, improved cell viability, decreased reactive oxygen species total levels and pro-inflammatory cytokine levels, increased anti-inflammatory cytokine levels, and accelerated the wound healing process. In conclusion, this is the first research to prove that cubiu is an important compound for use in the skin diseases, promoting skin wound healing, antimicrobial and anti-inflammatory activities.

Mancozeb is a fungicide widely used in agriculture, mostly against the pathogen Glomerella cingulata responsible for the rot of ripe grape, but presents high toxicity. Strategies are sought to reduce the toxicity of this fungicide and alternative treatments are welcome. An alternative could be the use of clove oil, which has Eugenol as its major compound, and has antifungal potential against G. cingulata, however, Eugenol is susceptible to degradation processes which may compromise its efficacy. The nanoencapsulation of Mancozeb and Eugenol is a possible strategy to overcome the limitations of toxicity, solubility and instability of these compounds. Therefore, the objective of this study is to develop nanoemulsions containing Mancozeb (0.1 mg/mL) and Eugenol (33 mg/mL), isolated or associated, and evaluate the safety of these formulations through cytotoxicity, genotoxicity and ecotoxicity tests. Nanoemulsions were developed by the spontaneous emulsification method, cytotoxicity and genotoxicity were evaluated in healthy human cells through MTT, Dichlorofluorescein diacetate and Picogreen tests, and ecotoxicity assessment was carried out using the chronic toxicity test in springtails. After preparation, the physicochemical characterization of the nanoemulsions were performed which presented mean particle size between 200 and 300 nm, polydispersity index less than 0.3, negative zeta potential and acid pH. The nanoencapsulation was able to avoid the reduction of the cell viability caused by Mancozeb, while Eugenol was shown to be safe for cell use in both free and nanostructured forms, however the association of the two active compounds showed toxicity in the higher doses of Mancozeb. In the ecotoxicity tests, both free Mancozeb and Eugenol forms presented high toxic potential for soil, whereas the nanoencapsulation of these compounds did not cause a reduction in number of springtails. Therefore, from the tests performed, it was possible to observe that nanoencapsulation of Mancozeb and Eugenol is a safe alternative for the application of these compounds mainly in agriculture.

The essential oil of Ocimum basilicum (common basil) is widely used in alternative medicine due its various therapeutic activities, however, it has limitations as to its stability. The nanoencapsulation of this oil aims to increase its stability and solubility, protecting against degradation processes and guaranteeing its therapeutic efficacy. In this study, nanoemulsions containing basil oil were developed with the objective of determining their stability and cytotoxicity in healthy human cells, in addition to evaluating their antioxidant and antimicrobial potential. The stability of the nanoemulsion containing basil oil was evaluated for 90 days, and the refrigeration condition (4 °C) was the one that best preserved the physicochemical characteristics of formulation. Both the free oil and the nanoemulsion presented low antioxidant activity, however, only the free oil caused a reduction in cell viability, whereas the nanoemulsion did not present cytotoxicity. The antimicrobial activity of the basil oil was potentiated after its nanoencapsulation against all evaluated microorganisms, being a stable, safe and effective antimicrobial alternative.

Trypanosoma evansi is a zoonotic parasite associated with high animal mortality that has gained importance due to its capacity to infect humans. Recently, some evidences have demonstrated that T. evansi infection causes severe genotoxic and cytotoxic damage in brain cells, contributing to the pathogenesis and clinical signs of the disease. In this sense, the aim of this study was to evaluate whether nerolidol-loaded in nanospheres, a natural compound with trypanocidal and neuroprotective effects, is able to protect the brain tissue from the cytotoxic and genotoxic effects found during T. evansi infections. Trypanosoma evansi induced brain genotoxic effects through increased damage index (DI) and frequency of damage (FD) when compared to the control group. Moreover, T. evansi induced cytotoxic effects through the reduction of brain cell viability compared to the control group. The metabolites of nitric oxide (NO x ) increased in infected animals compared to the control group. The treatment with nerolidol-loaded in nanospheres prevented the increase on brain DI, FD, and NO x levels, as well as the reduction on cell viability. Based on these evidences, these results confirm that T. evansi induces genotoxic and cytotoxic damage mediated by the upregulation of NO x levels. The most important finding is that nerolidol-loaded in nanospheres was able to prevent DNA damage and cell mortality through the modulation of brain NO x levels. In summary, this treatment can be considered an interesting approach to prevent T. evansi brain damage due its anti-inflammatory property.

The aim of this study was to evaluate the enzymatic activity of the purinergic system in sera samples from alloxan-induced diabetic mice treated with tucuma oil (Astrocaryum vulgare). For this, the mice were divided into four groups (n = 6): control/water (the group CW); control/tucuma oil (the group CT); diabetic/water (the group DW), and diabetic/tucuma oil (the group DT) treated for 14 days with 5.0 mL kg−1 via oral gavage. On day 14 post-treatment, mice were submitted to euthanasia and blood samples were collected by cardiac puncture. Tucuma oil treatment significantly decreased (p

Pelargonium graveolens is a member of the Geraniaceae family and has been used in folk medicine in many countries because of its anti-inflammatory activity. No studies have yet been reported to evaluate the anti-inflammatory activity of a nanoemulsion containing geranium oil (GO) model in macrophages. In this study the anti-inflammatory effect of Geranium nanoemulsion (NEG) macrophages induced with soluble proteins of Candida albicans was investigated. GO presented citronellol (17.74%) and geraniol (14.43%) as main constituents. The characterization in NEG was demonstrated, showing the particle size of 164 ± 3.5 nm, PDI of 0.12 ± 0.006 and zeta potential −10 mV ± 1.7. The MIC obtained for NEG and GO were 3.64 μg ml −1 and 1.82 μg ml −1 , respectively. The viability of the macrophages treated with NEG and GO concentrations (1/2 x, 1x and 2x MIC) was evaluated. There was a significant reduction of viability and the MTT assay was not confirmed after the LDH assay. Anti-inflammatory activity was evaluated by determining nitric oxide (NO), cytokines (interleukin IL-1, IL-6 and IL-10), tumor necrosis factor-α (TNF) and the expression levels gene of interleukin (IL-2), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The apoptosis inhibition capacity was assessed by determination of INFγ, caspase 3 and caspase 8. The results indicated that there was a significant increase of NO in the levels after treatment with NEG and significantly reduced levels after treatment with GO. The cytokines (IL-1, IL-6, IL-10, and TNF) were evaluated and NEG (½ x, 1x MIC) decreased IL-1 levels by 1.25–1.37 times, respectively. The NEG did not decrease IL-6 levels and a significant increase was observed for IL-10. GO significantly decreased IL-6 and IL-10 levels. There was a significant decrease in IL-2 and COX-2 levels and increased levels of iNOs. The levels of IFNγ and caspase-3 after treatment with NEG decreased indicating an anti-inflammatory effect and can inhibit apoptosis. Finally, the levels of caspase-8 do not change. Thus, pretreatment with NEG induced an anti-inflammatory effect against soluble proteins of C. albicans model macrophages.

Trypanosoma cruzi is a flagellated protozoan belonging to the Trypanosomatidae family, the etiologic agent of Chagas disease. Currently, there is neither a licensed vaccine nor effective treatment, characterizing an unmet clinical need. The IgY refers to the egg yolk immunoglobulin (Y = yolk) and its production and use are subjects of many studies due to the diversity of its diagnostic and therapeutic applications. Several researchers have shown that the use of specific IgY may prevent and/or control infectious and parasitic diseases. Based on these evidences, the aim of this study was to immunize chickens with trypomastigotes of T. cruzi in order to produce highly effective and pure antibodies (IgY), as well as extract, characterize, quantify, and verify cytotoxic effects of IgY anti-T. cruzi. After the induction of IgY production by chickens, the eggs were collected and the IgY was extracted by method of precipitation of polyethylene glycol 6000. The IgY anti-T. cruzi characterization was performed using polyacrylamide gel electrophoresis (SDS-PAGE), western-blot and enzyme-linked immunosorbent assay (ELISA). Moreover, the cytotoxic or proliferative effects of IgY anti-T. cruzi was verified by MTT assay. The concentration of IgY in yolk was 8.41 ± 1.47 mg/mL. The characterization of IgY reveled bands of stained peptides with molecular weight between 75 and 50 kDa and 37 and 25 kDa. In the ELISA test was observed that there was antigen-antibody reaction throughout the sample period. The concentrations of 1, 5 and 10 mg/mL of IgY anti-T. cruzi presented no cytotoxic of proliferative effects in mononuclear and VERO cells in vitro. The results indicated that T. cruzi is able to generate a high production of specific immunoglobulins in chickens, it did not cause damage to the cell membrane and no proliferative effect.

The aim of the study was to investigate the effect of the oral administration of tucuma oil (Astrocaryum vulgare) on glucose and insulin levels, oxidative status, and pancreatic genotoxic parameters of alloxan-induced diabetic mice. The animals were divided into four groups (n = 6 each): control/water; control/tucuma oil; diabetic/water; diabetic/tucuma oil treated for 14 days with 5.0 mL kg−1 via oral gavage. Gas chromatograph characterization demonstrated that oleic/elaidic fatty acid is the most abundant component present in this oil, followed by palmitic and stearic fatty acids. Our results demonstrated an increase (p

This study investigated the chemical constituents of Gaultheria procumbens essential oil and is the first to relate cytogenotoxicity with oxidative metabolism and antimicrobial activity. Chromatographic analysis of the essential oil showed methyl salicylate (99.96%) and linalool (0.04%) as the major compounds. The essential oil showed no signs of cytogenotoxicity at different concentrations (1.82 to 58.34 mg mL−1). Furthermore, G. procumbens essential oil and methyl salicylate were used to evaluate the minimal inhibitory concentrations (MIC) and minimal microbicidal concentrations (MMC). The results showed efficacy against several microorganisms, including Aeromonas caviae, Candida albicans, and Mycobacterium fortuitum with MIC values ranging from 1.82 to 3.64 mg mL−1 and MMC values ranging from 3.64 to 12.67 mg mL−1, which were confirmed by time-kill kinetics. Based on our results, the essential oil is a promising alternative to developing future formulations to treat infections caused by microorganisms.

Inflammatory dermatoses are prevalent worldwide, with impacts on the quality of life of patients and their families. The aim of this study was to determine the anti-inflammatory effects of Achyrocline satureioides oily extracts and nanocapsules on the skin using a mouse model of irritant contact dermatitis induced by croton oil, and a skin inflammation model induced by ultraviolet B (UVB) radiation. The mice were treated with 15 mg/ear oily extract (HG-OLAS) or nanocapsules (HG-NCAS) of A. satureioides incorporated into Carbopol® 940 hydrogels. We found that HG-OLAS and HG-NCAS formulations reduced ear edema in croton oil-induced lesions with maximum inhibitions of 54±7% and 74±3%, respectively. HG-OLAS and HG-NCAS formulations decreased ear edema induced by UVB radiation (0.5 J/cm2), with maximum inhibitions of 68±6% and 76±2% compared to the UVB radiation group, respectively. HG-OLAS and HG-NCAS modulated myeloperoxidase (MPO) activity after croton oil induction. Furthermore, croton oil and UVB radiation for 6 and 24 h, respectively, stimulated polymorphonuclear cells infiltration. The topical treatments reduced inflammatory processes, as shown by histological analysis. Together, the data suggest that topical application of A. satureioides oily extracts and nanocapsules produced antiedematogenic and anti-inflammatory effects. They constitute a compelling alternative for treatment of skin injuries.

Candida infection is an important cause of morbidity and mortality on immunosuppressed patients. This growing trend has been associated with resistance to the antimicrobial therapy and the ability of microorganism to form biofilms. TTO oil is used as antimicrobial which shows antibiofilm activity against Candida species. However, it presents problems due to its poor solubility and high volatility. The present study aimed to evaluate in vitro antibiofilm activity of TTO nanoparticles against many Candida species. It was performed the characterization of the oil and nanoparticles. The levels of exopolysaccharides, proteins, and the biomass of biofilms were measured. The chromatographic profile demonstrated that the TTO oil is in accordance with ISO 4730 with major constituents of 41.9% Terpinen-4-ol, 20.1% of γ-Terpinene, 9,8% of α-Terpinene, and 6,0% of 1,8-Cineole. The TTO nanoparticles showed pH of 6.3, mean diameter of 158.2 ± 2 nm, polydispersion index of 0.213 ± 0.017, and zeta potential of -8.69 ± 0.80 mV. The addition of TTO and its nanoparticles represented a significant reduction of biofilm formed by all Candida species, as well as a reduction of proteins and exopolysaccharides levels. It was possible to visualize the reduction of biofilm in presence of TTO nanoparticles by Calcofluor White method.

The aim of this study was to evaluate whether the treatment with Achyrocline satureioides essential oil-loaded in nanocapsules (AS-NC) is able to protect the hepatic tissue against cytotoxic damage caused by Trypanosoma evansi. Thus, the rats were divided into four groups (n = 6 per group): uninfected/saline, uninfected/AS-NC, infected/saline, and infected/AS-NC. At day 4 post-infection (PI), the animals were euthanized and liver and sera samples were collected to perform the hepatic cell viability assay, and to determine seric levels of reactive oxygen species (ROS) and nitric oxide metabolites (NOx). Cell viability decreased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this alteration in infected rats. Seric ROS and NOx levels increased (p < 0.05) in the infected/saline group compared to uninfected/saline group, while the treatment with AS-NC avoided this effect on ROS levels of infected rats. In summary, the treatment with AS-NC was able to protect the liver tissue against the cytotoxic effect caused by the parasite by avoiding exacerbated production of ROS.

The effect of the combination of α-pinene and β-caryophyllene on the proliferation of the Trypanosoma evansi was analyzed. These compounds were added individually and in combination at different concentrations to T. evansi cultures, and the in vivo study used mice of 1.0 and 1.5 mL kg −1 of α-pinene and β-caryophyllene individually and in combination against T. evansi . In order to evaluate the in vitro safety, lymphocytes and VERO cells were assessed using tetrazolium salt (MTT) assay. The trypanocidal effect of α-pinene and β-caryophyllene was observed in vitro when applied independently or combined at 0.5, 1 and 2% concentrations. The combination effect showed a faster trypanocidal effect when compared to chemotherapy (diminazene aceturate – D.A.). Concerning the in vivo evaluation, α-pinene + β-caryophyllene at 1.0 mL kg −1 was able to extend animal longevity and showed 83.33% curative efficacy, a superior result when compared to D.A. (16.66%). The MTT assay showed that the assessed compounds do not present toxicity to used cells. Also, in vivo safety evaluation of α-pinene + β-caryophyllene at 1.0 mL kg −1 not altered the aminotransferases levels in serum. Combination between α-pinene and β-caryophyllene shows in vitro and in vivo trypanocidal activity against T. evansi , in a safe dose.

Inga semialata (Vell.) C. Mart. belongs to the family Fabaceae. It is known for its therapeutic properties, highlighting its antimicrobial and antioxidant potential. The objective of the present work was to obtain crude extract leaves of Inga semialata, to identify and quantify active compounds, to evaluate the antioxidant potential of the crude extract in vitro, as well as to determine its antimicrobial activity. The crude extract was obtained by the maceration process. The identified and quantified of compounds present in the crude extract of Inga semialata was performed by high performance liquid chromatography. The evaluation of the antioxidant potential of the extract was realized by in vitro tests (DPPH, diacetate dichlorofluorescein test and nitric oxide test) and the evaluation of the antimicrobial activity was carried out using the minimum inhibitory concentration methodology.

Cyclooxygenase-2 (COX-2) is one of the two isoforms of COX producing prostaglandins derived from arachidonic acid. COX-2 is the inducible isoform expressed in many cell types in response to cytokines and pro-inflammatory molecules. In brain, COX-2 is frequently associated with pro-inflammatory activities, and its increase is related to neurodegenerative processes in acute and chronic diseases. Thus, the aim of this study was to evaluate the COX-2 immunoreactivity and the frequency damage caused by T. evansi infection on days 5 and 15 post-infection (PI) in hippocampus cells, as well as the relationship with behavioral alterations. Decreased (p

The aim of this study was to evaluate the therapeutic efficacy and safety of using 3′deoxyadenosine (Cordycepin – adenosine analogue) combined with deoxycoformycin (Pentostatin – an adenosine deaminase inhibitor) in mice infected with Trypanosoma evansi. We show that the combination of Cordycepin (2.0 mg kg−1) and Pentostatin (0.2, 0.5, 1.0, 2.0 mg kg1) is effective in the clearance of T. evansi, although at the higher concentrations of Pentostatin 2 mg kg−1 some toxicity was observed in the liver and kidney. Since the Cordycepin 2.0 mg kg−1 and Pentostatin 0.2 mg kg−1 combination was effective and had low toxicity, we recommend this as a therapeutic option for a T. evansi mouse model.

This study quantifies the bioactive molecules in and determines the in vitro protective effect of ethanolic extracts isolated from the peel and pulp of tucumã (Astrocaryum aculeatum, Mart.), an Amazonian fruit rich in carotenoids. The cytoprotective effect of tucumã was evaluated in lymphocyte cultures exposed to H2O2 using spectrophotometric, fluorimetric, and immunoassay assays. The results confirmed that tucumã pulp extract is rich in β-carotene and quercetin, as previously described in the literature. However, high levels of these compounds were also found in tucumã peel extract. The extracts also contained significant amounts rutin, gallic acid, caffeic acid, and chlorogenic acid. Despite quantitative differences in the concentration of these bioactive molecules, both extracts increased the viability of cells exposed to H2O2 in concentrations ranging from 300 to 900μg/mL. Caspases 1, 3, and 8 decreased significantly in cells concomitantly exposed to H2O2 and these extracts, indicating that tucumã cryoprotection involves apoptosis modulation.

Astrocaryum aculeatum, popularly known as tucuma, belongs to Arecaceae family and is also called tucuma-do-amazonas, tucumanzeiro, tucuma-grande, or tucuma-accu. This palm tree is native to the Amazon, occurring in northern Bolivia, Colombia, Venezuela, Guyana, Suriname, and Brazil being found mainly in the state of Amazonas. It is a large palm tree, with an upright stipe of 10–30 m, being covered in its upper half by black or brown thorns arranged in rings. The leaves have a feather shape and have thorns on its entire length, measuring 4–5 m long. The productivity of the palm tree is around 12–50 kg/year, which starts slowly and late, when the tree reaches 7 years at least with height between 6 and 9 m. The fruit weighs 20–100 grams and is yellowish-green, with a length of 4.5–6.0 and 3.5 cm–4.5 cm in diameter. The pulp has a coloration ranging from yellow to orange and has 9% protein, 55% oil, and represents 22% of the fruit weight. A number of substances have been identified: carotenoids (62.6 mg/g of fresh pulp), being 21 isoforms, with a predominance of 75% of all-trans beta-carotene; flavonoids like catechin and quercetin and ascorbic acid (58 mg/100 g). It is currently consumed by the Amazon population, with the use of nearly all the plants. The stipe is applied to the construction of houses and furniture. The meristem is used in food. The flesh of the fruit, which is the edible part, is widely used for the production of tucuma wine, ice cream, popsicles, soap, as well as animal feed. The core is used for the production of handicrafts, such as rings, bracelets, and necklaces. Furthermore, the core has been widely used to extract an oil to be used in the cosmetic and food industry, and in the production of biodiesel. The leaves have been used in the production of baskets, hats and Tucum (a high-quality fiber for the production of hammocks and bags) is extracted from them. Recent studies, suggest that the hydroalcoholic extract of tucuma has an antioxidant capacity quite high and also has some action in modulating the production of free radicals in healthy blood exposed to hydrogen peroxide. These results indicate that tucuma may have chemotherapeutic potential.

This study aimed to verify the effect of the treatment with A. satureioides essential oil (free and nanoencapsulated forms) and diminazene aceturate on hematological and biochemical variables in rats infected by Trypanosoma evansi. The 56 rats were divided into seven groups with eight rats each. Groups A, C and D were composed by uninfected animals, and groups B, E, F and G were formed by infected rats with T. evansi. Rats from groups A and B were used as negative and positive control, respectively. Rats from the groups C and E were treated with A. satureioides essential oil, and groups D and F were treated with A. satureioides nanoencapsulated essential oil. Groups C, D, E and F received one dose of oil (1.5 mL kg(-1)) during five consecutive days orally. Group G was treated with diminazene aceturate (D.A.) in therapeutic dose (3.5 mg kg(-1)) in an only dose. The blood samples were collected on day 5 PI for analyses of hematological (erythrocytes and leukocytes count, hemoglobin concentration, hematocrit, mean corpuscular and mean corpuscular hemoglobin concentration) and biochemical (glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, urea and creatinine) variables. A. satureioides administered was able to maintain low parasitemia, mainly the nanoencapsulated form, on 5 days post infection. On the infected animals with T. evansi treated with A. satureioides essential oil (free and nanocapsules) the number of total leucocytes, lymphocytes and monocytes present was similar to uninfected rats, and different from infected and not-treated animals (leukocytosis). Treatment with A. satureioides in free form elevated levels of ALT and AST, demonstrating liver damage; however, treatment with nanoencapsulated form did not cause elevation of these enzymes. Finally, treatments inhibited the increase in creatinine levels caused by infection for T. evansi. In summary, the nanoencapsulated form showed better activity on the trypanosome; it did not cause liver toxicity and prevented renal damage.

The aim of this study was to evaluate the effects of treatment with free and nanoencapsulated essential oil of Achyrocline satureioides on trypanosomosis and its oxidative/antioxidants variables in liver and kidney of rats infected experimentally with Trypanosoma evansi. For that, 48 rats were divided into six groups (A-F), eight animals each group. Groups A, C and D were composed of uninfected animals, while animals in groups B, E and F were inoculated intraperitoneally with T. evansi. Groups A and B were used as controls, negative and positive, respectively. Groups C and E receive oil (orally), as well as the animals in groups D and F were treated with nanoencapsulated essential oil. The treatment was not able to eliminate the parasites, but it remained the levels of parasitemia low. The carbonyl levels in liver and kidney did not differ between groups. Infected animals (group B) showed an increase in the TBARS levels and a decrease in the CAT activity and NPSH levels in liver and kidney, compared with the same parameters in the control (group A). Treatment with A. satureioides (groups C and D) did not influence the TBARS levels and CAT activity in the liver, but it increased the CAT activity in kidneys of the animals of group C. NPSH levels decreased in liver in the groups treated with nanoencapsulated essential oil (groups D and F). An interesting result observed was that the animals infected and then treated with essential oil of A. satureioides (groups E and F) did not differ from animals of group A for TBARS, CAT and NPSH, unlike what happened with the animals of group B. Therefore, the treatment with essential oil did not eliminate the parasites from the bloodstream, but it reduced the number of trypanosomes, mainly by its nanoencapsulated form. The same occurred with the lipid peroxidation in the liver. However, the treatments reduced the oxidative damage, and it led to the activation of the antioxidant enzymes. We believe that the association of this natural product with a trypanocidal drug may enhance its curative effect.

The aim of this study was to investigate the effects of Trypanosoma evansi infections on arterial blood gases of experimentally infected rats. Two groups with eight animals each were used; group A (uninfected) and group B (infected). Infected animals were daily monitored through blood smears that showed high parasitemia with 30 trypanosomes per field (1000×) on average, 5days post-infection (PI). Arterial blood was collected at 5days PI for blood gas analysis using an automated method based on dry-chemistry. Hydrogen potential (pH), partial oxygen pressure (pO2), oxygen saturation (sO2), sodium (Na), ionic calcium (Ca ionic), chlorides (Cl), partial dioxide carbon pressure (pCO2), base excess (BE), base excess in the extracellular fluid (BEecf), bicarbonate (cHCO3), potassium (K), lactate, and blood total dioxide the carbon (tCO2) were evaluated. The levels of pH, pCO2, BE, BEecf, cHCO3, and tCO2 were significantly decreased (P

The aim of this study was to verify the trypanocidal effectiveness of aqueous, methanolic, and ethanolic extracts of Achyrocline satureioides against Trypanosoma evansi in vitro. A. satureioides extracts, known as macela, were used on trypomastigotes at different concentrations (1, 5, 10, 50, 100, 500, and 1,000 µg/ml) and exposure times (0, 1, 3, 6, and 9 hr). A dose-dependent effect was observed when the 3 extracts were tested. The concentrations of 1, 5, and 10 µg/ml were not able to kill trypomastigotes until 3 hr after exposure, and the highest concentrations (500 and 1,000 µg/ml) were able to kill all trypomastigotes after 1 hr. When the time of exposure was increased up to 9 hr, the concentrations at 50 and 100 µg/ml were 100% effective to 3 extracts. The chemical analysis of the extracts revealed the presence of flavonoids, a trypanocidal compound already described. Based on the results, we can conclude that the A. satureioides extracts exhibit trypanocidal effects.

Tucuma (Astrocaryum aculeatum) is an Amazonian fruit that presents high levels of carotenoids and other bioactive compounds such as quercetin. The extracts of tucuma peel and pulp present strong antioxidant activity which illustrate an elevated concentration that causes cytotoxic effects in human peripheral blood mononuclear cells (PBMCs). This study performed additional investigations to analyze the potential genotoxic effects of the tucuma extracts on PBMCs. The genotoxicity was evaluated by DNA fragmentation, Comet assay, and chromosomal instability G-band assays. The acute tucuma extract treatment showed genoprotective effects against DNA denaturation when compared with untreated PBMC cells. However, in the experiments with 24 and 72 h treatments to tucuma treatments, we observed low genotoxicity through a concentration of 100 μg/mL, some genotoxic effects related to intermediary concentrations (100-500 μg/mL), and more pronounced genotoxic effects on higher tucuma extract concentrations. After 24 h of treatment, the reactive oxygen species were similar among treatments and PBMC control groups. However, the caspase-1 activity related to the apoptosis and pyroptosis process increased significantly in higher tucuma concentrations. In summary, tucuma extracts, despite their higher antioxidant content and antioxidant activity, would present PBMCs genotoxic effects that are dependent on concentration and time exposition. These results need to be considered in future in vitro and in vivo studies of tucuma effects.

Essential oil of Eucalyptus globulus presents several pharmacological properties. However, their therapeutic efficacy may be affected by limitations due to several conditions, rendering it difficult to obtain stable and effective pharmaceutical formulations. The use of nanotechnology is an alternative to improve their characteristics aiming to ensure their stability and effectiveness. Furthermore, studies about the possible toxic effects of nanostructures are necessary to evaluate safety when the formulation comes into contact with human cells. Hence, in this paper, we evaluate for the first time the stability and in vitro cytogenotoxicity of nanoemulsions containing Eucalyptus globulus in peripheral blood mononuclear cells. As a result, the stability study found that the best condition for storage up to 90 days was refrigeration (4°C); it was the condition that best preserved the nanometric features. The content of the major compounds of oil was maintained after nanoencapsulation and preserved over time. In tests to evaluate the safety of this formulation, we can conclude that, at a low concentration (approximately 0.1%), Eucalyptus globulus nanoemulsion did not cause toxicity in peripheral blood mononuclear cells and also showed a protective effect in cells against possible damage when compared to oil in free form.

The aims of this study were to develop nerolidol-loaded nanospheres, and to evaluate their efficacy in vitro and in vivo against Trypanosoma evansi, as well as to determine their physicochemical properties, morphology, and any possible side effect in vitro against peripheral blood mononuclear cell (PBMC). The nanospheres showed an adequate particle size (149.5 nm), narrow particle distribution (0.117), negative zeta potential (-12.8 mV), and pH of 6.84, such as observed by transmission electron microscopy. In vitro, a trypanocidal effect of nerolidol and nanospheres containing nerolidol was observed at 0.5, 1.0, and 2.0%, i.e., both treatments showed a faster trypanocidal effect compared to chemotherapy (diminazene aceturate - D.A.). T. evansi infected mice were used to evaluate the effects of nerolidol-loaded nanospheres regarding pre-patent period, longevity, and therapeutic efficacy. Oral administration of nerolidol-loaded nanospheres at 1.0 mL/kg/day during 10 days increased mice survival (66.66%) compared to 0% and 33.33% of mice survival when treated with nerolidol in its free form and D.A., respectively. Cytotoxic study indicated that both treatments showed no side effects in vitro against PBMC, an important marker used in toxicological surveys. Therefore, nanoencapsulation increased the therapeutic efficacy of nerolidol against T. evansi, and can be used as an alternative treatment for T. evansi infection.

Trypanosoma evansi is an important pathogen that causes changes in nitric oxide (NO) levels and antioxidant enzymes, as well as oxidative stress. The present study evaluated the in vivo effect of T. evansi infection on frequency and index of DNA damage in liver, heart, spleen and total blood of rats. Twenty rats were assigned into two groups with ten rats each, being subdivided into four subgroups (A1 and A2, 5 animals/group; and B1 and B2, 5 animals/group). Rats in the subgroups A1 and A2 were used as control (uninfected) and animals in the subgroups B1 and B2 were inoculated with T. evansi (infected). NO in serum and the comet assay were used to measure DNA damage index (DI) and damage frequency (DF) in liver, heart, spleen and total blood of infected rats. Increased NO levels on days 3 and 9 post-infection (PI) was observed (P

Several compounds present in fruits as polyphenols are able to kill or inhibit the growth of microorganisms. These proprieties are relevant mainly in tropical areas, as Amazonian region where infectious are highly prevalent. Therefore, this study investigated the antimicrobial activity of tucuma Amazonian fruit against 37 microorganisms. The potential role of oxidative metabolism imbalance was also studied as causal mechanism of antimicrobial activity. The results showed antibacterial effect of pulp and peel tucuma hydro-alcoholic extracts on three Gram-positive bacteria (Enterococcus faecalis, Bacillus cereus, Listeria monocytogenes) and antifungal effect against Candida albicans. The antimicrobial contribution of main chemical compounds (quercetin, rutin, β-carotene and gallic, caffeic and chlorogenic acids) found in tucuma extracts was also investigated showing an inhibitory effect depending of the organism mainly by quercetin in bacteria and rutin in C. albicans. Analysis of kinetic of DNA releasing in extracellular medium by fluorescence using DNA Pico Green assay(®) and reactive oxygen species production (ROS) showed potential oxidative imbalance contribution on tucuma inhibitory effect. In B. cereus and C. albicans this effect was clear since after 24h the ROS levels were higher when compared to negative control group. In conclusion, tucuma extracts present antimicrobial activity to four microorganisms that have large problems of drug resistance, and the possible mechanism of action of this Amazon fruit is related to REDOX imbalance.