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The search for bioactive compounds in natural products holds promise for discovering new pharmacologically active molecules. This study explores the anti-inflammatory potential of açaí (Euterpe oleracea Mart.) constituents against the NLRP3 inflammasome using high-throughput molecular modeling techniques. Utilizing methods such as molecular docking, molecular dynamics simulation, binding free energy calculations (MM/GBSA), and in silico toxicology, we compared açaí compounds with known NLRP3 inhibitors, MCC950 and NP3-146 (RM5). The docking studies revealed significant interactions between açaí constituents and the NLRP3 protein, while molecular dynamics simulations indicated structural stabilization. MM/GBSA calculations demonstrated favorable binding energies for catechin, apigenin, and epicatechin, although slightly lower than those of MCC950 and RM5. Importantly, in silico toxicology predicted lower toxicity for açaí compounds compared to synthetic inhibitors. These findings suggest that açaí-derived compounds are promising candidates for developing new anti-inflammatory therapies targeting the NLRP3 inflammasome, combining efficacy with a superior safety profile. Future research should include in vitro and in vivo validation to confirm the therapeutic potential and safety of these natural products. This study underscores the value of computational approaches in accelerating natural product-based drug discovery and highlights the pharmacological promise of Amazonian biodiversity.
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Anti-Inflamatórios , Inflamassomos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Inflamassomos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Euterpe/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
The NLRP3 inflammasome plays a crucial role in the inflammatory response, reacting to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This response is essential for combating infections and restoring tissue homeostasis. However, chronic activation can lead to detrimental effects, particularly in neuropsychiatric and neurodegenerative diseases. Our study seeks to provide a method to effectively measure the NLRP3 inflammasome's activation within cerebral organoids (COs), providing insights into the underlying pathophysiology of these conditions and enabling future studies to investigate the development of targeted therapies.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Organoides , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Organoides/metabolismo , Inflamassomos/metabolismo , Humanos , Animais , Encéfalo/metabolismoRESUMO
Nowadays, bone systems have a series of consequences that compromise the quality of life mainly due to wear and decreased bioactivity, generally in elderly people and children. In this context, the combination of montmorillonite (MMT-NPs) in a vitreous system such as nanobioglass facilitates the adsorption of biomolecules on the surface and within the interlamellar spaces, enabling the entry of ions by a cation exchange process focusing on increasing the rate of bone formation. This work aims to synthesize and characterize an eco-friendly hybrid reinforcement containing MMT-NPs with nanobioglass doped with magnesium nanoparticles (MgNPs-BV). In this way, MMT-NPs@MgNPs-BV was synthesized by the impregnation method, where an experimental design was used to verify the synthesis conditions. The ideal condition by experimental design was carried out in terms of the characterization and biological activity, where we demonstrated MMT-NPs of 30% w w-1, MgNPs-BV of 6% w w-1, and a calcination temperature of 1273.15 K with a cell viability around 66.87%, an average crystallite diameter of 12.5 nm, and a contact angle of 17.7°. The characterizations confirmed the impregnation method with an average particle size of 51.4 ± 13.1 nm. The mechanical tests showed a hardness of 2.6 GPa with an apparent porosity of 22.2%, similar to human bone. MMT-NPs@MgNPs-BV showed a cell proliferation of around 96% in osteoblastic cells (OFCOL II), with the formation of the apatite phase containing a relation of Ca/P of around 1.63, a biodegradability of 82%, and rapid release of ions with a Ca/P ratio of 1.42. Therefore, the eco-friendly hybrid reinforcement with MMT-NPs and MgNPs-BV shows potential for application with a matrix for biocompatible nanocomposites for bone regeneration.
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Bentonita , Nanopartículas , Criança , Humanos , Idoso , Qualidade de Vida , Regeneração Óssea , ÍonsRESUMO
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for the global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a vital role in mediating viral replication and transcription. In this study, a comprehensive computational approach was employed to investigate the binding affinity, selectivity, and stability of natural product candidates as potential new antivirals acting on the viral polyprotein processing mediated by SARS-CoV-2 Mpro. A library of 288 flavonoids extracted from Brazilian biodiversity was screened to select potential Mpro inhibitors. An initial filter based on Lipinski's rule of five was applied, and 204 compounds that did not violate any of the Lipinski rules were selected. The compounds were then docked into the active site of Mpro using the GOLD program, and the poses were subsequently re-scored using MM-GBSA (Molecular Mechanics Generalized Born Surface Area) binding free energy calculations performed by AmberTools23. The top five flavonoids with the best MM-GBSA binding free energy values were selected for analysis of their interactions with the active site residues of the protein. Next, we conducted a toxicity and drug-likeness analysis, and non-toxic compounds were subjected to molecular dynamics simulation and free energy calculation using the MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. It was observed that the five selected flavonoids had lower MM-GBSA binding free energy with Mpro than the co-crystal ligand. Furthermore, these compounds also formed hydrogen bonds with two important residues, Cys145 and Glu166, in the active site of Mpro. Two compounds that passed the drug-likeness filter showed stable conformations during the molecular dynamics simulations. Among these, NuBBE_867 exhibited the best MM-PBSA binding free energy value compared to the crystallographic inhibitor. Therefore, this study suggests that NuBBE_867 could be a potential inhibitor against the main protease of SARS-CoV-2 and may be further examined to confirm our results.
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The neuroinflammatory process is considered one of the main characteristics of central nervous system diseases, where a pro-inflammatory response results in oxidative stress through the generation of reactive oxygen and nitrogen species (ROS and RNS). Olive (Olea europaea L.) pomace is a by-product of olive oil production that is rich in phenolic compounds (PCs), known for their antioxidant and anti-inflammatory properties. This work looked at the antioxidant and anti-neuroinflammatory effects of the bioavailable PC from olive pomace in cell-free models and microglia cells. The bioavailable PC of olive pomace was obtained through the process of in vitro gastrointestinal digestion of fractionated olive pomace (OPF, particles size < 2 mm) and micronized olive pomace (OPM, particles size < 20 µm). The profile of the PC that is present in the bioavailable fraction as well as its in vitro antioxidant capacity were determined. The anti-neuroinflammatory capacity of the bioavailable PC from olive pomace (0.03-3 mg L-1) was evaluated in BV-2 cells activated by lipopolysaccharide (LPS) for 24 h. The total bioavailable PC concentration and antioxidant activity against peroxyl radical were higher in the OPM than those observed in the OPF sample. The activation of BV-2 cells by LPS resulted in increased levels of ROS and nitric oxide (NO). The bioavailable PCs from both OPF and OPM, at their lowest concentrations, were able to reduce the ROS generation in activated BV-2 cells. In contrast, the highest PC concentration of OPF and OPM was able to reduce the NO levels in activated microglial cells. Our results demonstrate that bioavailable PCs from olive pomace can act as anti-neuroinflammatory agents in vitro, independent of particle size. Moreover, studies approaching ways to increase the bioavailability of PCs from olive pomace, as well as any possible toxic effects, are needed before a final statement on its nutritional use is made.
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CONTEXT: Heparin, one of the drugs reused in studies with antiviral activity, was chosen to investigate a possible blockade of the SARS-CoV-2 spike protein for viral entry through computational simulations and experimental analysis. Heparin was associated to graphene oxide to increase in the binding affinity in biological system. First, the electronic and chemical interaction between the molecules was analyzed through ab initio simulations. Later, we evaluate the biological compatibility of the nanosystems, in the target of the spike protein, through molecular docking. The results show that graphene oxide interacts with the heparin with an increase in the affinity energy with the spike protein, indicating a possible increment in the antiviral activity. Experimental analysis of synthesis and morphology of the nanostructures were carried out, indicating heparin absorption by graphene oxide, confirming the results of the first principle simulations. Experimental tests were conducted on the structure and surface of the nanomaterial, confirming the heparin aggregation on the synthesis with a size between the GO layers of 7.44 Å, indicating a C-O type bond, and exhibiting a hydrophilic surface characteristic (36.2°). METHODS: Computational simulations of the ab initio with SIESTA code, LDA approximations, and an energy shift of 0.05 eV. Molecular docking simulations were performed in the AutoDock Vina software integrated with the AMDock Tools Software using the AMBER force field. GO, GO@2.5Heparin, and GO@5Heparin were synthesized by Hummers and impregnation methods, respectively, and characterized by X-ray diffraction and surface contact angle.
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COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Simulação de Acoplamento Molecular , Glicoproteína da Espícula de Coronavírus/metabolismo , Heparina/metabolismo , SARS-CoV-2/metabolismo , Antivirais/farmacologiaRESUMO
Microglial activation has been associated to the physiopathology of neurodegenerative diseases, such as schizophrenia, and can occur during inflammation and oxidative stress. Pharmacological treatment is associated with severe side effects, and studies for use of plant extracts may offer alternatives with lower toxicity. Harpagophytum procumbens (HP) is a plant known for its anti-inflammatory properties. In the present study, we characterized the ethyl acetate fraction of HP (EAF HP) by ESI-ToF-MS and investigated the effects EAF HP in a lipopolysaccharide (LPS) induced inflammation model on microglial cells (BV-2 lineage). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), DCFH-DA (2',7'-dichlorofluorescein diacetate) and cell cycle flow cytometer analysis were performed. In vivo was investigated the amphetamine-induced psychosis model through behavioral (locomotor and exploratory activities, stereotypies and working memory) and biochemical (DCFH-DA oxidation and protein thiols) parameters in cortex and striatum of mice. EAF HP reduced activation and proliferation of microglial cells in 48 h (300 µg/mL) and in 72 h after treatments (50-500 µg/mL). Reactive oxygen species levels were lower at the concentration of 100 µg/mL EAF HP. We detected a modulatory effect on the cell cycle, with reduction of cells in S and G2/M phases. In mice, the pre-treatment with EAF HP, for 7 days, protected against positive and cognitive symptoms, as well as stereotypies induced by amphetamine. No oxidative stress was observed in this amphetamine-induced model of psychosis. Such findings suggest that EAF HP can modulate the dopaminergic neurotransmission and be a promising adjuvant in the treatment of locomotor alterations, cognitive deficits, and neuropsychiatric disorders.
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Harpagophytum , Animais , Camundongos , Anfetamina/farmacologia , Harpagophytum/química , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Estresse OxidativoRESUMO
Antibiotic resistance associated with pulmonary infection agents has become a public health problem, being considered one of the main priorities for immediate resolution. Thus, to increase the therapeutic options in the fight against resistant microorganisms, the synthesis of molecules from pre-existing drugs has shown to be a promising alternative. In this sense, the present work reports the synthesis, characterization, and biological evaluation (against fungal and bacterial agents that cause lung infections) of potential metallodrugs based on sulfamethoxazole complexed with AuI, AgI, HgII, CdII, NiII, and CuII. The minimal inhibitory concentration (MIC) value was used to evaluate the antifungal and antibacterial properties of the compounds. In addition, it was also evaluated the antibiofilm capacity in Pseudomonas aeruginosa, through the quantification of its biomass and visualization using atomic force microscopy. For each case, molecular docking calculations were carried out to suggest the possible biological target of the assayed inorganic complexes. Our results indicated that the novel inorganic complexes are better antibacterial and antifungal than the commercial antibiotic sulfamethoxazole, highlighting the AgI-complex, which was able to inhibit the growth of microorganisms that cause lung diseases with concentrations in the 2-8 µg mL-1 range, probably at targeting dihydropteroate synthetase - a key enzyme involved in the folate synthesis. Furthermore, sulfamethoxazole complexes were able to inhibit the formation of bacterial biofilms at significantly lower concentrations than free sulfamethoxazole, probably mainly targeting the active site of LysR-type transcriptional regulator (PqsR). Overall, the present study reports preliminary results that demonstrate the derivatization of sulfamethoxazole with transition metal cations to obtain potential metallodrugs with applications as antimicrobial and antifungal against pulmonary infections, being an alternative for drug-resistant strains.
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Antifúngicos , Sulfametoxazol , Sulfametoxazol/farmacologia , Antifúngicos/farmacologia , Simulação de Acoplamento Molecular , Antibacterianos/química , Biofilmes , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosaRESUMO
Richardia brasiliensis is a species used in folk medicine and rich in active compounds. In this study, the extracts were submitted to UHPLC-ESI-MS/MS analysis and total polyphenols, tannins, and flavonoids assays. Besides, it was determined its antioxidant capacity, oxidative stress markers and toxicological profile. Fourteen polyphenols were found and, in the dosages, a slight change in the concentrations in each extract was observed. Regarding the antioxidant capacity, the responses were different in the methods used. There was an increase in lipid peroxidation, and NO, however total ROS remained unchanged. The cells remained more than 90% viable and the extracts did not cause damage to single strands of DNA, with the exception of the crude autumn and spring extracts at 500 µg/mL. The results found in this study suggest that extracts are potentially toxic to human leukocyte cells in high concentrations; however, more studies should be performed in different cell lines.
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Antioxidantes , Rubiaceae , Humanos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectrometria de Massas em Tandem , Taninos , Polifenóis/farmacologia , Compostos Fitoquímicos/análise , Flavonoides/farmacologia , Flavonoides/análiseRESUMO
Curcumin is an active polyphenol substance found in the highest concentrations in the roots of Curcuma longa. Its health benefits have led to recent increases in the consumption of curcumin. It has anti-inflammatory and antioxidant activities and is a potent neuroprotective against diseases of the brain. Nevertheless, its low bioavailability and its relative difficulty crossing the blood-brain barrier limit curcumin's use for these purposes. Curcumin-loaded nanoparticles may be an effective treatment for several diseases although there is a paucity of studies reporting its safety in the central nervous system (CNS). Therefore, this study aimed to identify non-neurotoxic concentrations of free curcumin and two nanoformulations of curcumin. Cell lines BV-2 and SH-SY5Y, both originating from the CNS, were evaluated after 24, 48, and 72 h of treatment with free curcumin and nanocapsules We measured viability, proliferation, and dsDNA levels. We measured levels of reactive oxygen species and nitric oxide as proxies for oxidative stress in culture supernatants. We found that free curcumin was toxic at 10 and 20 µM, principally at 72 h. Nanoformulations were more neurotoxic than the free form. Safe concentrations of free curcumin are between 1-5 µM, and these concentrations were lower for nanoformulations. We determined the ideal concentrations of free curcumin and nanocapsules serving as a basis for studies of injuries that affect the CNS.
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Curcumina , Nanocápsulas , Neuroblastoma , Humanos , Curcumina/farmacologia , Nanocápsulas/toxicidade , Linhagem Celular , Estresse OxidativoRESUMO
Haemonchus contortus is a highly pathogenic and prevalent helminth that causes many deaths in sheep herds. Anthelmintics are usually employed to overcome this issue; however, they do not guarantee immediate and lasting efficacy because of the occurrence of drug-resistant parasites. Among substances that are used in scientific studies for parasitic control, essential oils are known to have different pharmacological properties. However, they demonstrate instability owing to several factors, and therefore, nanoemulsification is considered an alternative to control the instability and degradability of these compounds. The objective of this study was to evaluate the cytotoxicity of nanoemulsions containing essential oil of Eucalyptus globulus against the blood of healthy sheep and to verify their activity against the parasite H. contortus in sheep. The results presented adequate nanotechnological characteristics (diameter 72 nm, PDI 0.2, zeta -11 mV, and acidic pH) and adequate morphology. Further, the corona effect and cytotoxic profiles of the free oil and nanoemulsion against blood cells from healthy sheep were evaluated. The tests results did not present a toxicity profile. For evaluating efficacy, we observed an important anthelmintic action of the nanoemulsion containing oil in comparison to the free oil; the results demonstrate a potential role of the nanoemulsion in the inhibition of egg hatchability and the development of larvae L1 to L3 (infective stage). Based on these results, we developed an important and potential anthelmintic alternative for the control of the parasite H. contortus.
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Anti-Helmínticos , Hemoncose , Haemonchus , Óleos Voláteis , Doenças dos Ovinos , Animais , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/toxicidade , Óleo de Eucalipto/farmacologia , Hemoncose/tratamento farmacológico , Hemoncose/parasitologia , Hemoncose/veterinária , Larva , Óleos Voláteis/química , Óleos Voláteis/toxicidade , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologiaRESUMO
Richardia brasiliensis, known as poaia branca, is a medicinal species widely distributed throughout Brazil and used in folk medicine. However, studies on its toxicity are practically non-existent, and little is known about its biological activity. This study aimed to investigate its phytochemical compounds, assess its in vitro and in vivo toxicities, and determine its antiproliferative activity. UHPLC-ESI-HRFTMS performed the phytochemical characterization, and the antiproliferative activity was analyzed in different tumor cell lines. In vitro toxicity was evaluated in PBMC cells, and in vivo acute and repeated dose toxicity was evaluated according to OECD guidelines. It was identified alkaloids and terpenes as significant compounds. Regarding its antiproliferative activity, the human melanoma strain decreased its viability by about 95%. In vitro toxicity showed that the extracts maintained the viability of PBMCs; however, higher concentrations were able to increase the production of dsDNA quantity. In vivo tests showed no mortality nor signs of toxicity; the alterations found in hematological and biochemical parameters are within the standards for the species. The results indicate that R. brasiliensis has a good effect against the tumor cell line; still, more studies on its toxicity at higher concentrations are needed.
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Alcaloides , Leucócitos Mononucleares , Linhagem Celular Tumoral , Humanos , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/toxicidadeRESUMO
Cancer is considered a multifactorial disease and its development could be associated with several factors, for example, rotenone exposition. Unfortunately, many cancers are resistant to chemotherapy, as cervical cancer. Regarding this, lemongrass is a remarkable natural product that presents antioxidant and anticancer activities, which could show therapeutic action against rotenone and cervical cancer. Thus, this study aimed to investigate the antioxidant and anticancer action of lemongrass. An in vitro study was conducted using VERO (kidney cells) and SiHa cell lines (cervical cancer cells). VERO cells were exposed to rotenone and lemongrass extract for 24 and 72 h. While SiHa cells were exposed to lemongrass isolated and associated to chemotherapy, 5-fluorouracil, during 24 and 48 h. After, levels of viability, proliferation, and oxidative metabolism were determined. The results showed that lemongrass presents antioxidant activity on VERO cells by increasing cell viability and proliferation and decreasing oxidative stress caused by rotenone. Moreover, lemongrass showed anticancer activity by decreasing cell viability and increasing oxidative stress parameters on SiHa. Besides, lemongrass had no alteration in the chemotherapy activity. Therefore, this study revealed that lemongrass presents antioxidant and anticancer activity since it can protect against the cytotoxicity of rotenone and reduce the cell viability of cervical cancer.
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Cymbopogon , Neoplasias do Colo do Útero , Animais , Antioxidantes/farmacologia , Chlorocebus aethiops , Feminino , Humanos , Rotenona , Neoplasias do Colo do Útero/tratamento farmacológico , Células VeroRESUMO
Ferulic acid (FA) is a phenolic compound that has antioxidant, anti-inflammatory and anticarcinogenic properties besides presenting cytoprotective activity. It has limited oral bioavailability what is a challenge to its therapeutic application. In this way, this investigation aimed to develop FA-loaded nanocapsule suspensions (NC-FA) prepared with ethylcellulose and evaluate their in vitro release profile, mucoadhesion and irritation potential; scavenging capacity, cytotoxicity, cytoprotection and genoprotection against hydrogen peroxide-induced damage in hMNC (human Mononucleated Cells) culture. The nanocapsules presented physicochemical characteristics compatible with colloidal systems (NC-FA: 112 ± 3 nm; NC-B (without FA): 107 ± 3 nm; PdI < 0.2; Span<2.0 and negative zeta potential). In addition, the nanoparticulate system promoted the FA controlled release, increasing the half-life twice through the in vitro dialysis method. NC-FA and NC-B were able to interact with mucin, which is an indicative of mucoadhesive properties and the association of FA with nanocapsules showed decreased irritation by HET-CAM method. Besides, the NC-FA did not present cytotoxicity in hMNC and improved the ATBS radical scavenging capacity. Besides, it prevented, treated and reversed oxidative conditions in a H2O2-induced model in hMNC. Thus, this nanocarrier formulation is promising to perform more preclinical investigations focusing on diseases involving oxidative mechanisms.
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Antioxidantes/administração & dosagem , Ácidos Cumáricos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanocápsulas/química , Animais , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Células Cultivadas , Celulose/análogos & derivados , Embrião de Galinha , Ácidos Cumáricos/farmacocinética , Ácidos Cumáricos/farmacologia , Humanos , Peróxido de Hidrogênio/toxicidade , Irritantes , Linfócitos , Mucinas , Nanocápsulas/efeitos adversosRESUMO
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.
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Rubiaceae , Espectrometria de Massas em Tandem , Dano ao DNA , Hemólise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espécies Reativas de OxigênioRESUMO
Achyrocline flaccida aqueous extract was obtained by macerating wildflowers. The phytochemical profile present in the A. flaccida aqueous extract was elucidated by HPLC-ESI-MS/MS. Toxicity was evaluated in vitro by comet assay in peripheral blood mononuclear cells (PBMCs) and in vivo using Caenorhabditis elegans as a model. The antioxidant activity was also evaluated, and antimycobacterial activity was assessed by the broth microdilution method. The compounds present in the aqueous extract mainly belonged to the flavonoid class (89%). The concentrations that showed protective effects in C. elegans against oxidative stress and antimycobacterial activity had no toxic effects. The antimycobacterial activity test demonstrated that the concentration of 1,560 µg mL-1 inhibited the growth and eradication of the mycobacterial tested strains. Based on our findings, the A. flaccida aqueous extract presents a viable potential in developing new phytotherapeutic drugs against mycobacteria of clinical relevance.
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Achyrocline , Asteraceae , Achyrocline/química , Animais , Antibacterianos/farmacologia , Antioxidantes/química , Asteraceae/química , Brasil , Caenorhabditis elegans , Leucócitos Mononucleares , Extratos Vegetais/química , Espectrometria de Massas em TandemRESUMO
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.
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Arecaceae , Nanoestruturas , Antioxidantes/química , Emulsões/química , Nanoestruturas/químicaRESUMO
INTRODUCTION: Neuropsychiatric diseases are responsible for one of the highest burden of morbidity and mortality worldwide. These illnesses include schizophrenia, bipolar disorder, and major depression. Individuals affected by these diseases may present mitochondrial dysfunction and oxidative stress. Additionally, patients also have increased peripheral and neural chronic inflammation. The Brazilian fruit, açaí, has been demonstrated to be a neuroprotective agent through its recovery of mitochondrial complex I activity. This extract has previously shown anti-inflammatory effects in inflammatory cells. However, there is a lack of understanding of potential anti-neuroinflammatory mechanisms, such as cell cycle involvement. OBJECTIVE: The objective of this study is to evaluate the anti-neuroinflammatory potential of an açaí extract in lipopolysaccharide-activated BV-2 microglia cells. METHODS: Açaí extract was produced and characterized through high performance liquid chromatography. Following açaí extraction and characterization, BV-2 microglia cells were activated with LPS and a dose-response curve was generated to select the most effective açaí dose to reduce cellular proliferation. This dose was then used to assess reactive oxygen species (ROS) production, double-strand DNA release, cell cycle modulation, and cytokine and caspase protein expression. RESULTS: Characterization of the açaí extract revealed 10 bioactive molecules. The extract reduced cellular proliferation, ROS production, and reduced pro-inflammatory cytokines and caspase 1 protein expression under 1 µg/mL in LPS-activated BV-2 microglia cells but had no effect on double strand DNA release. Additionally, açaí treatment caused cell cycle arrest, specifically within synthesis and G2/Mitosis phases. CONCLUSION: These results suggest that the freeze-dried hydroalcoholic açaí extract presents high anti-neuroinflammatory potential.
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Euterpe , Microglia , Extratos Vegetais , Animais , Linhagem Celular , Citocinas/metabolismo , Euterpe/química , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
The aim of this study was to evaluate the toxicity of tucumã oil nanocapsules from the Amazon region in silver catfish, Rhamdia quelen. Fish were exposed to water treated with different concentrations of tucumã nanocapsules, white, solubilized oil and surfactant vehicles. After three days of exposure, fish were euthanized and liver, gills and brain removed for analysis of the dichlorofluorescein, nitric oxide and PicoGreen® assays. Plasma was collected for assay of hepatic transaminases. The nanocapsules had a diameter of 221 ± 1.27 nm, confirmed by atomic force microscopy. The oil nanocapsules were not toxic to this species of fish, but white nanocapsules and surfactant increased the levels of reactive oxygen species. Thus, nanocapsules are promising for the transport of tucumã oil. In view of the anti-inflammatory properties of this oil, it is possible to envisage its application in skin diseases for example, since they present essentially inflammatory conditions.HighlightsThe most abundant carotenoid in tucumã oil was all-trans-beta-carotene.Nanocapsules are good carriers for tucumã oil.Tucumã oil nanocapsules does nothas toxicity effect in catfish.
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Peixes-Gato , Nanocápsulas , Animais , Brânquias , Fígado , Modelos TeóricosRESUMO
Microbial infections caused by sessile microorganisms are known to be a more challenging issue than infections caused by the same microorganisms in the planktonic state. Pseudomonas aeruginosa is an opportunistic pathogen and biofilm-forming agent. This species presents intense cellular communication mediated by signaling molecules. This process is known as quorum sensing (QS) and induces the transcription of specific genes that favors cell density growth and three-dimensional bacterial grouping. In this context, the discovery of compounds capable of inhibiting the action of the QS signaling molecules seems to be a promising strategy against biofilms. This work aimed to evaluate the anti-biofilm action and the in vitro safety profile of a sulfamethoxazole-Ag complex. The results obtained indicate potential anti-biofilm activity through QS inhibition. In silico tests showed that the compound acts on the las and pqs systems, which are the main regulators of biofilm formation in P. aeruginosa. Additionally, the molecule proved to be safe for human peripheral blood mononuclear cells.