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The importance of essential oils and their components in the industrial sector is attributed to their chemical characteristics and their application in the development of products in the areas of cosmetology, food, and pharmaceuticals. However, the pharmacological properties of this class of natural products have been extensively investigated and indicate their applicability for obtaining new drugs. Therefore, this review discusses the use of these oils as starting materials to synthesize more complex molecules and products with greater commercial value and clinic potential. Furthermore, the antiulcer, cardiovascular, and antidiabetic mechanisms of action are discussed. The main mechanistic aspects of the chemopreventive properties of oils against cancer are also presented. The data highlight essential oils and their derivatives as a strategic chemical group in the search for effective therapeutic agents against various diseases.
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Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.
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This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.
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Gallic acid (GA) has antioxidant, anti-inflammatory and antimicrobial properties, while ellagic acid (EA) demonstrates anticancer, antiviral and photoprotective activity. In this study, the combination of these substances incorporated into a poloxamer gel was tested to verify the individual effect of the substances, in addition to taking advantage of a probable complementary effect, aiming to provide additional therapeutic benefits. As a result of the incorporation, formulations containing GA, EA and GA + EA were obtained, which were evaluated for the effects of the Freeze-thaw cycle on pH, which revealed a significant decrease (p < 0.05) in most samples, including the vehicle (without drug) and the gel containing both drugs. No sample showed variation outside the normal pH range for the skin, with values ranging from 4.8 to 6.0. Regarding conductivity, the GA, EA and GA + EA formulations showed a reduction (p < 0.05) after the freeze-thaw cycle. The drug content in the formulations ranged from 95.86% to 101.35% initially to 91.30% to 101.51% after the freeze-thaw cycle. Regarding the drug release, the results revealed the following cumulative percentages: GA-3% - 92.58% after 1.5 h; AE-3% - 51.60% after 6 h; GA + EA (1.5% = 1.5%) - 99.91% after 2 h; GA + EA- (1.5% = 1.5%) released 57.06%, after 6 h. Regarding toxicity, it was observed that the group treated with GA showed a lower survival rate of the larvae (40%) at the dose 3000 mg/Kg in the formulation. Following the same trend, in the acute lethal concentration (ALC50) test performed using Zophobas morio larvae, an ALC50 of 2191.51 mg/Kg was observed for GA at 48 h. Melanin analysis showed a decrease in concentrations of 30 mg/Kg in the GA group, 3 mg/Kg of EA and 3, 300, 3000 mg/Kg of GA + EA, of the pure drugs. In the groups with the drugs incorporated into the gel, there was a significant decrease (P < 0.05) in melanin in the vehicle (gel), at concentrations of 300 and 3000 mg/Kg of GA and EA. On the other hand, in the combination of GA + EA, a reduction was observed at concentrations of 3 and 30 mg/Kg when compared to the control group. Thus, the gel showed good quality as a pharmaceutical formulation for topical use and low toxicity, making it promising for use in skin therapies.
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Ácido Elágico , Ácido Gálico , Animales , Ácido Gálico/farmacología , Ácido Elágico/toxicidad , Ácido Elágico/química , Larva , Melaninas , Antioxidantes/farmacologíaRESUMEN
Monoterpenes are secondary metabolites of plants belonging to the terpenoid class of natural products. They are the most abundant components of essential oils that are generally considered to have various pharmacological properties. These compounds are reported to have antidiabetic effects in recent years. Due to nature's complex biosynthetic machinery, they also exhibit a reasonable degree of structural complexity/diversity for further analysis in structure-activity studies. Therefore, monoterpenes as antidiabetic agents have been investigated by recent in vitro and in vivo studies extensively reported in the scientific literature and claimed by patent documents. The purpose of this survey is to provide a comprehensive and prospective review concerning the potential applications of monoterpenes in the treatment of diabetes. The data for this research were collected through the specialized databases PubMed, Scopus, Web of Science, and ScienceDirect between the years 2014 and 2022, as well as the patent databases EPO, WIPO, and USPTO. The research used 76 articles published in the leading journals in the field. The main effect observed was the antidiabetic activity of monoterpenes. This review showed that monoterpenes can be considered promising agents for prevention and/or treatment of diabetes as well as have a marked pharmaceutical potential for the development of bioproducts for therapeutics applications.
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In the search for anxiolytic drugs with fewer adverse effects, calcium blockers were proposed as a benzodiazepines (BZDs) alternative. In this context, the anxiolytic effect of nimodipine has been demonstrated. However, its low bioavailability and solubility could be improved by using nanostructured drug delivery systems such as liposomes. In this way, liposomal formulation containing nimodipine (NMD-Lipo) was developed. The NMD-lipo is a formulation capable of improving the kinetic characteristics of the drug, as well as the anxiolytic effect of nimodipine. In this work, the serotonergic system participation in the anxiolytic mechanism of the liposomal formulation containing nimodipine (NMD-Lipo) was investigated. A possible 5-HT1A receptor mediation on the NMD-Lipo anxiolytic effect was demonstrated by using WAY 100635 (5-HT1A receptor antagonist) since the antagonist reversed the NMD-Lipo anxiolytic effect in the light/dark test and elevated plus maze test. The results demonstrated that the NMD-Lipo administration had anxiolytic activity through 5-HT1A receptors without causing sedation or compromising the motor coordination of the tested animals.
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Croton cajucara Benth showed several pharmacological properties such as: anti-inflammatory, antinociceptive hypoglycemic, lipid-lowering, antiulcer, antiestrogenic, antitumor, antigenotoxic, antimutagenic, and cardiovascular. The 19-nor-clerodane diterpene trans-dehydrocrotonin (t-DCTN or DCTN) is the major bioactive constituent extracted from the bark of this Croton. Patents for Croton cajucara Benth in the period 2015 to 2022 comprises 14 published documents. Among them 4 patents are colloidal systems (SM/SNEDDS) loading t-DCTN for pharmacological applications. Patent registrations highlighted the huge promising biotechnological potential of Croton cajucara Benth especially in the phytotherapy field, and the correlation with its bioactive constituents of which t-DCTN showed the foremost results, so this herbal could become an alternative in the treatment of Covid-19. However, investigation of more recently published patents for clerodane diterpenes with similar chemical structure of t-DCTN, who previously showed antiviral property must be carried out and should be searched on several patent data bases.
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This research was aimed at evaluating the relationship between the estimated polyphenol intake and the atherogenic lipid profile in adult and elder residents in the city of Teresina, located in the Northeastern Region of Brazil. This study was a cross-sectional population-based survey with 501 adults and elders, conducted in Teresina, Brazil. Food intake was obtained by 24-h food recall. The estimated polyphenol intake was calculated by multiplying the food consumption data from the recall by the polyphenol content in the foods described in the Phenol-Explorer database. The mean intake of total polyphenols was 1006.53 mg/day. The phenolic acids was the class with the highest intake, followed by the flavonols. Coffee, beans and apples were the main foods contributing to the total polyphenol intake. In the individuals with elevated serum concentrations of total cholesterol and triglycerides, the intake of total polyphenols was significantly higher. The intake of total polyphenols, phenolic acids and lignans was higher in the subjects with dyslipidemia. This article provides, for the first time, data on the intake of the total polyphenol classes and subclasses in the evaluated population and the relationship with the lipid profile. The individuals with a higher intake of total polyphenols had a worse lipid profile, which may be a consequence of an improved diet in those individuals who present with dyslipidemia.
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Fenoles , Polifenoles , Humanos , Adulto , Anciano , Brasil , Estudios Transversales , LípidosRESUMEN
The present study investigates the relationship between the consumption of ultra-processed foods (UPF) and anthropometric indices of body composition in adults and seniors living in Teresina, the state capital of an area in northeastern Brazil. The article seeks to address two questions: Is UPF consumption linked to worsening body composition in different age groups? Do anthropometric indicators of body composition change with the increasing consumption of UPF? The study is a cross-sectional, household, population study, carried out with 490 adults and seniors. The food consumption was obtained with a 24 h food recall, and the foods were classified using NOVA. Anthropometric indicators evaluated were waist-to-height ratio, triceps skinfold thickness, arm circumference, corrected arm muscle area, subscapular skinfold thickness, and calf circumference. The association between energy contribution of UPF with anthropometric indicators was verified with a simple and multiple linear regression analysis. Individuals aged 20 to 35 years showed a significant association between UPF consumption and skinfold thickness (ß: 0.04; CI: 0.03/0.09), demonstrating an increase in this subcutaneous body fat marker with higher UPF consumption. Moreover, in participants aged 36 to 59 years, an inverse correlation between UPF intake and muscle mass markers, arm circumference (ß: -0.02; confidence interval: -0.03/-0.01), and corrected arm muscle area (ß: -0.07; confidence interval: -0.12/-0.02) were observed. Such results suggest there is decreased muscle mass with increasing UPF consumption. This is the first study that verified an association between UPF consumption and low-cost body composition indicators in different age groups.
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Comida Rápida , Alimentos Procesados , Humanos , Adulto , Brasil , Estudios Transversales , Composición Corporal , Manipulación de Alimentos , DietaRESUMEN
The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC50 = 0.059 ± 0.008 µg/mL) or carbachol (EC50 = 0.068 ± 0.007 µg/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children.
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Lycopene is a carotenoid with potential use in the treatment of chronic illnesses. Here, different formulations of lycopene were studied: lycopene-rich extract from red guava (LEG), purified lycopene from red guava (LPG) and a self-emulsifying drug delivery system loaded with LPG (nanoLPG). The effects of administering orally various doses of LEG to hypercholesterolemic hamsters were evaluated regarding the liver function of the animals. The cytotoxicity of LPG in Vero cells was analyzed by a crystal violet assay and by fluorescence microscopy. In addition, nanoLPG was employed in stability tests. LPG and nanoLPG were tested for their cytotoxic effect on human keratinocytes and antioxidant capacity on cells in an endothelial dysfunction model in an isolated rat aorta. Finally, the effect of different nanoLPG concentrations on the expression of immune-related genes (IL-10, TNF-α, COX-2 and IFN-γ) from peripheral blood mononuclear cells (PBMC) using real-time PCR was also analyzed. Results suggest that LEG, despite not being able to improve blood markers indicative of liver function in hypercholesterolemic hamsters, reduced hepatic degenerative changes. Additionally, LPG did not show cytotoxicity in Vero cells. In relation to nanoLPG, the effects produced by heat stress evaluated by Dynamics Light Scattering (DLS) and visually were loss of color, texture change and phase separation after 15 days without interfering with the droplet size, so the formulation proved to be efficient in stabilizing the encapsulated lycopene. Although LPG and nanoLPG showed moderate toxicity to keratinocytes, which may be related to cell lineage characteristics, both revealed potent antioxidant activity. LPG and nanoLPG showed vasoprotective effects in aortic preparations. The gene expression assay indicates that, although no significant differences were observed in the expression of IL-10 and TNF-α, the PBMCs treated with nanoLPG showed a reduction in transcriptional levels of IFN-γ and an increased expression of COX-2. Thus, the work adds evidence to the safety of the use of lycopene by humans and shows that tested formulations, mainly nanoLPG due to its stability, stand out as promising and biosafe products for the treatment of diseases that have oxidative stress and inflammation in their etiopathology.
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Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. ß-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of ß-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. ß-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC50 = 2.78 µM) and axenic amastigotes (EC50 = 1.12 µM) at concentrations non-toxic to RAW 264.7 macrophages (CC50 = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. ß-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC50 = 0.89 µM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that ß-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays.
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Hydrogels are structures that have value for application in the area of tissue engineering because they mimic the extracellular matrix. Naturally obtained polysaccharides, such as chitosan (CH) and cashew gum, are materials with the ability to form polymeric networks due to their physicochemical properties. This research aimed to develop a scaffold based on chitosan and phthalated cashew tree gum and test it as a support for the growth of human mesenchymal stem cells. In this study, phthalation in cashew gum (PCG) was performed by using a solvent-free route. PCG-CH scaffold was developed by polyelectrolyte complexation, and its ability to support adherent stem cell growth was evaluated. The scaffold showed a high swelling rate. The pore sizes of the scaffold were analyzed by scanning electron microscopy. Human dental pulp stem cells (hDPSCs) were isolated, expanded, and characterized for their potential to differentiate into mesenchymal lineages and for their immunophenotypic profile. Isolated mesenchymal stem cells presented fibroblastoid morphology, plastic adhesion capacity, and differentiation in osteogenic, adipogenic, and chondrogenic lineages. Mesenchymal stem cells were cultured in scaffolds to assess cell adhesion and growth. The cells seeded on the scaffold showed typical morphology, attachment, and adequate distribution inside the matrix pores. Thus, cells seeded in the scaffold may improve the osteoinductive and osteoconductive properties of these biomaterials.
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Acinetobacter baumannii is an important opportunistic pathogen that causes serious health-related infections, especially in intensive care units. The present study aimed to investigate the antimicrobial activity of Riparin-B (Rip-B) alone and in association with norfloxacin against multidrug-resistant clinical isolates of A. baumannii. For this, the minimum inhibitory concentrations were determined by the microdilution method. For the evaluation of resistance-modulating activity, MIC values for antibiotics were determined in the presence or absence of subinhibitory concentrations of Rip-B or chlorpromazine (CPZ). The AdeABC-AdeRS efflux system genes from these isolates were detected by PCR. Docking studies were also carried out to evaluate the interaction of Riparin-B and the AdeABC-AdeRS efflux system. The study was conducted from 2017 to 2019. The results showed that Rip-B showed weak intrinsic activity against the strains tested. On the other hand, Rip-B was able to modulate norfloxacin's response against A. baumannii strains that express efflux pump-mediated resistance. Docking studies provided projections of the interaction between Rip-B and EtBr with the AdeB protein, suggesting that Rip-B acts by competitive inhibition with the drug. Results found by in vitro and in silico assays suggest that Rip-B, in combination with norfloxacin, has the potential to treat infections caused by multidrug-resistant A. baumanni with efflux pump resistance.
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Menthofuran is a monoterpene present in various essential oils derived from species from Mentha genus, and in Brazil, those species are widely used in treating gastrointestinal and respiratory disorders. Considering the wide pharmacological potential of monoterpenes, including their antioxidant activity, this study aimed to evaluate menthofuran-gastroprotective activity, as well as the involvement of antioxidant mechanisms in this effect. The acute toxicity was evaluated according to the fixed dose method. The antiulcerogenic activity was investigated by using experimental models of gastric ulcers induced by ethanol, indomethacin, and ischemia/reperfusion in rats. The antisecretory gastric activity, the catalase activity, and the gastric wall mucus were determined in pylorus ligated rats. Gastric wall nonprotein sulfhydryl (NPSH) group content, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) content were evaluated in ethanol-induced the gastric ulcer model. Menthofuran (2 g/kg) presented low acute toxicity and showed gastroprotective activity against ethanol-, indomethacin-, and ischemia/reperfusion-induced ulcers. Moreover, menthofuran presented antisecretory activity, reduced the total acidity, and increased pH of gastric secretion. On the other hand, a decrease in mucus content of gastric wall without alteration of gastric juice volume and catalase activity was observed. Interestingly, menthofuran increased NPSH levels and reduced MDA levels and MPO activity. Gastroprotective effects of menthofuran appear to be mediated, at least in part, by the NOS pathway, endogenous prostaglandins, reduced gastric juice acidity, increased concentration of the NPSH groups, and reduced lipidic peroxidation. These findings support the menthofuran as an effective gastroprotective agent, as well as the marked participation of antioxidant mechanisms in this response.
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The aim of this review was to (i) acknowledge structural advantages of natural products (NPs) for designing therapeutic drugs; (ii) emphasize how wildlife conservation is socially and economically necessary for scientific and commercial progress in Brazilian regions; and (iii) show how decisions by governmental regulations exert damaging effects on safeguarding of biodiversity. Natural products (NPs) from animals (e.g.: bufadienolides as marinobufagin), plants (diterpenes: casearin X and paclitaxel; triterpenes: betulinic acid) and microorganisms (depsipeptides: geodiamolides; antraciclines: doxorubicin) are the main source of oral drugs and have innate advantages for enteral and parenteral drug design, synthesis and combinational chemistry using novel techniques, including green chemistry. NPs possess high chemical diversity, binding flexibility to biological targets, chiral centers, aliphatic systems, hydrogen-bond acceptors and donors, and/or heteroatoms, and broad-spectrum pharmacological properties, including against malign disorders. Nonetheless, all Brazilian biomes and connected ecosystems have been systemically threatened since 2019 by the following fire, deforestation, monocultures, cattle raising, mining and/or oil spills mainly as consequence of financial cuts in key institutions which oversee environmental stability for terrestrial and marine Brazilian fauna and flora. Nevertheless, natural chemical entities, broad traditional knowledge on agrobiodiversity, fishing, fire management, and pioneering processes of economic interest play a vital role for "Science of Biodiversity," which arises as business bioeconomy opportunities to convert Brazil into a self-sufficient country for production of pharmaceutical supplies, cosmeticsand foods. Hence, Brazil needs sustainable development projects supported by government and scientific input if one wishes to use the chemical and biological biodiversity to treat individuals and improve the quality of life.
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Productos Biológicos , Ecosistema , Animales , Bovinos , Brasil , Calidad de Vida , Biodiversidad , Desarrollo de Medicamentos , Conservación de los Recursos Naturales/métodosRESUMEN
INTRODUCTION: Previous studies have reported that buriti (Mauritia flexuosa L. f.) is a typical fruit from the Brazilian cerrado ecosystem and an important food source for low-income populations. Its composition is rich in carotenoid polyphenols, monounsaturated fatty acids, and ascorbic acid. However, studies on the biological effects resulting from the consumption of this fruit are scarce. OBJECTIVE: To evaluate the effects of a diet supplemented with buriti (Mauritia flexuosa L. f.) on kidney and liver functions in growing rats. METHODS: Determination of centesimal composition, carotenoids, and fatty acids content for buriti pulp, standard chow, and butiti-supplemented chow were performed. Then, Wistar rats of both sexes were fed a standard diet or supplemented with buriti pulp. Blood samples were collected at the end of the experiment to determine biochemical parameters. The unpaired t-test was applied, and differences were considered significant when p<0.05. RESULTS: A diet enriched with buriti pulp did not interfere with kidney function and most markers of liver function in animals. Alkaline phosphatase showed significantly higher plasma concentration in female rats, and albumin and uric acid showed lower concentrations in male rats in both experimental groups. CONCLUSION: The changes observed in biochemical markers did not provide evidence of adverse effects of buriti pulp supplementation on liver function. Thus, the intake of buriti pulp can be encouraged as it is a low-cost food source for the general population.
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Animales , Masculino , Femenino , Ratas , Roedores , Dieta , Frutas/metabolismo , Riñón , Hígado , BrasilRESUMEN
Conventional treatments for leishmaniasis have caused serious adverse effects, poor tolerance, development of resistant strains. Natural products have been investigated as potential therapeutic alternatives. The cashew nut shell liquid (CNSL) is a natural source of phenolic compounds with several biological activities, where cardanol (CN) is considered one of the most important and promising compounds. This study aimed to evaluate antileishmanial, cytotoxic and immunomodulatory activities of CNSL and CN. Both showed antileishmanial potential, with IC50 for CNSL and CN against Leishmania infantum: 148.12 and 56.74 µg/mL; against Leishmania braziliensis: 85.71 and 64.28 µg/mL; against Leishmania major: 153.56 and 122.31 µg/mL, respectively. The mean cytotoxic concentrations (CC50) of CNSL and CN were 37.51 and 31.44 µg/mL, respectively. CNSL and CN significantly reduced the percentage of infected macrophages, with a selectivity index (SI) >20 for CN. CNSL and cardanol caused an increase in phagocytic capacity and lysosomal volume. Survival rates of Zophobas morio larvae at doses of 3; 30 and 300 mg/kg were: 85%, 75% and 60% in contact with CNSL and 85%, 60% and 40% in contact with CN, respectively. There was a significant difference between the survival curves of larvae when treated with CN, demonstrating a significant acute toxicity for this substance. Additional investigations are needed to evaluate these substances in the in vivo experimental infection model.
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Anacardium , Antineoplásicos , Nueces , Fenoles/toxicidadRESUMEN
Isopropyl gallate (IPG) is a polyphenol obtained from alterations in the gallic acid molecule via acid catalysis with previously reported leishmanicidal and trypanocidal activities. The present study aims to evaluate in silico binding activity towards some targets for antileishmanial chemotherapy against Leishmania major species, and ADMET parameters for IPG, as well as in vitro antileishmanial and cytotoxic effects. Molecular docking was performed using AutoDockVina and BIOVIA Discovery Studio software, whereas in silico analysis used SwissADME, PreADMET and admetSAR software. In vitro antileishmanial activity on promastigotes and amastigotes of Leishmania major, cytotoxicity and macrophages activation were assessed. IPG exhibited affinity for pteridine reductase (PTR1; -8.2 kcal/mol) and oligopeptidase B (OPB; -8.0 kcal/mol) enzymes. ADMET assays demonstrated good lipophilicity, oral bioavailability, and skin permeability, as well as non-mutagenic, non-carcinogenic properties and low risk of cardiac toxicity for IPG. Moreover, IPG inhibited the in vitro growth of promastigotes (IC50 = 90.813 µM), presented significant activity against amastigotes (IC50 = 13.45 µM), promoted low cytotoxicity in macrophages (CC50 = 1260 µM), and increased phagocytic capacity. These results suggest IPG is more selectively toxic to the parasite than to mammalian cells. IPG demonstrated acceptable in silico pharmacokinetics parameters, and reduced infection and infectivity in parasitized macrophages, possibly involving macrophage activation pathways and inhibition of leishmania enzymes.
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In the present study, the effects of cryolipolysis on one and multiple body areas, assessing body composition, lipid profile and peroxidation and inflammatory markers were investigated. Twenty-four women aged between 20 and 59 years were randomly assigned to three groups: (1) control, (2) cryolipolysis on the abdomen and (3) cryolipolysis on the abdomen + flanks. Anthropometric measurements, bioimpedance and ultrasound were performed, as well serum lipid profile, lipid peroxidation markers (malondialdehyde and myeloperoxidase) and inflammatory markers (C-reactive protein and Interleukin-1ß) were determined. In addition, food consumption and physical activity level were evaluated. Data were obtained at 0, 10 and 30 days (t0, t10 and t30) after cryolipolysis. Cryolipolysis did not change anthropometric measurements, body composition or lipid profile. Interestingly, the abdomen + flanks group had significantly increased plasma myeloperoxidase activity at t0, t10 and t30, and increased malondialdehyde levels at t0 and t10 when compared to the other groups. Furthermore, there were no differences between macronutrient intake and total energy value, physical activity level, malondialdehyde and interleukin-1ß at t30. Cryolipolysis did not change body composition, lipid profile or inflammatory markers investigated. On the other hand, when used on the abdomen and flanks, it produced an increase in lipid peroxidation markers, malondialdehyde and myeloperoxidase.