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1.
Nat Prod Res ; : 1-7, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963903

ABSTRACT

Mangaba is a fruit native to Brazil, rich in bioactive compounds. To evaluate physicochemical composition, bioactive compounds, antioxidant and antifungal activity of mangaba fruit pulp. Moisture, ash, protein, lipid, energy values and phenolic compounds were determined. Antioxidant activity was determined by capture of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Evaluation of antifungal activity was performed by Minimum Inhibitory Concentration, according to protocols M07-A9 and M27-S3, and minimum fungicidal concentration. Freeze-dried mangaba pulp presented high levels of carbohydrates, low levels of lipids, and high energy density. Phenolic analysis demonstrated that chlorogenic acid was found in the highest concentration, followed by p-coumaric acid and ferulic acid. Mangaba extract showed antioxidant activity like BHT. Mangaba extract inhibited the growth of Candida albicans (ATCC 90028), Cryptococcus gattii (AFLP4), Candida guilliermondii (ATCC 6260) and Candida albicans (MYA 2876). Freeze-dried mangaba inhibited fungal activity associated with antioxidant effect due to presence of phenolic compounds.

2.
ScientificWorldJournal ; 2024: 8991384, 2024.
Article in English | MEDLINE | ID: mdl-38957454

ABSTRACT

The medicinal plant Bredemeyera floribunda Willd. is used to treat cardiovascular disease, chronic fatigue, low libido, as well as increased diuresis. However, studies considering the toxicity of this plant are scarce. Develop an aqueous extract of B. floribunda considering traditional use and determine the average lethality (LD50), signs, and symptoms of toxicity. The B. floribunda extract was obtained by immersing the root bark in ultrapure water for 18 hours at 4°C, under constant stirring. The test extract was administered in a single dose of 2.000 mg/kg by gavage to rats. Signs and symptoms of toxicity were determined according to the Hippocratic screening test and compared with the control group. In addition, a necropsy was performed for macroscopic evaluation of the organs in the abdominal cavity. A powder was obtained from aqueous extracts that showed the same organoleptic characteristics and emulsification capacity as those presented by the fresh root when prepared according to popular tradition. The LD50 was greater than the test dose with three animals surviving. On the other hand, necropsy of dead rats showed necrosis and reduction in lung mass, in addition to the presence of foam and excessive distension of the stomach and intestines. The main symptoms of toxicity were anesthesia, ataxia, sedation, loss of muscle strength, and excessive drowsiness in the first 24 hours. There was no difference between the control and extract groups with regard to body mass, food, and water intake, as well as in macroscopy of the heart, liver, lungs, intestines, spleen, pancreas, and kidneys. The aqueous extract of the B. floribunda was considered nontoxic or of very low toxicity. However, it is capable of altering the activity of the central nervous system and causing disorders in the respiratory and digestive systems.


Subject(s)
Plant Bark , Plant Extracts , Plant Roots , Animals , Plant Extracts/toxicity , Plant Extracts/chemistry , Rats , Plant Bark/chemistry , Male , Plant Roots/chemistry , Lethal Dose 50 , Female , Toxicity Tests, Acute , Rats, Wistar , Models, Animal
3.
J Med Food ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695868

ABSTRACT

Given the importance of discovering plant species from the Brazilian Cerrado biome with anticancer potential, this study evaluated the antitumor activity of two extracts of Campomanesi adamantium fruits in in vitro and in vivo models of melanoma lung metastasis. Pulp and peel extracts (DEGPU and DEGPE, respectively) were extracted from fresh fruit using dichloromethane as a solvent. As cytotoxicity parameter, concentration values that inhibited 50% cell growth (GI50), total growth inhibition (TGI), and selectivity index (SI) were established. The melanoma lung metastasis model was obtained by injecting 5 × 105/50 µL B16-F10 cells via the tail vein of mice, which received treatment on the 15th day. Metastatic lungs were collected for fluorescence analysis with the IR-780 marker and also macro- and microscopic assessment. In vitro analyses showed that DEGPU was active in K562 (GI50 32.99; TGI 47.93) and U-251 (GI50 32.10; TGI 249.92), whereas DEGPE showed better cytotoxicity results for all tumor cell lines, but was more efficient in K562 (GI50 27.42; TGI 40.20) and U-251 (GI50 4.89; TGI 12.77). Both showed a cytocidal effect on B16F10 at the highest concentration tested, with approximately 25% (DEGPU) and 88% (DEGPE) of cell death. In vivo analyzes showed that both extracts showed significant activity in metastatic lung. Fluorescence images showed differences in intensity between groups owing to greater tumor involvement. Macro- and microscopic images showed that treatments with extracts limited tumor growth and prevented proliferation. The extracts tested have promising activity, thus requiring further research on their active compounds.

4.
Biochim Biophys Acta Gen Subj ; 1868(5): 130583, 2024 May.
Article in English | MEDLINE | ID: mdl-38360076

ABSTRACT

Antimicrobial peptides (AMP) represent an alternative in the treatment of fungal infections associated with countless deaths. Here, we report a new AMP, named KWI-19, which was designed based on a peptide encrypted in the sequence of an Inga laurina Kunitz-type inhibitor (ILTI). KWI-19 inhibited the growth of Candida species and acted as a fungicidal agent from 2.5 to 20 µmol L-1, also showing synergistic activity with amphotericin B. Kinetic assays showed that KWI-19 killed Candida tropicalis cells within 60 min. We also report the membrane-associated mechanisms of action of KWI-19 and its interaction with ergosterol. KWI-19 was also characterized as a potent antibiofilm peptide, with activity against C. tropicalis. Finally, non-toxicity was reported against Galleria mellonella larvae, thus strengthening the interest in all the bioactivities mentioned above. This study extends our knowledge on how AMPs can be engineered from peptides encrypted in larger proteins and their potential as candicidal agents.


Subject(s)
Antifungal Agents , Candida , Animals , Antifungal Agents/pharmacology , Amphotericin B/pharmacology , Peptides/pharmacology , Candida tropicalis , Protease Inhibitors , Peptide Hydrolases
5.
Arch Biochem Biophys ; 753: 109884, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38218361

ABSTRACT

The spread of fungi resistant to conventional drugs has become a threatening problem. In this context, antimicrobial peptides (AMPs) have been considered as one of the main alternatives for controlling fungal infections. Here, we report the antifungal and antibiofilm activity and some clues about peptide RQ18's mechanism of action against Candida and Cryptococcus. This peptide inhibited yeast growth from 2.5 µM and killed all Candida tropicalis cells within 2 h incubation. Moreover, it showed a synergistic effect with antifungal agent the amphotericin b. RQ18 reduced biofilm formation and promoted C. tropicalis mature biofilms eradication. RQ18's mechanism of action involves fungal cell membrane damage, which was confirmed by the results of RQ18 in the presence of free ergosterol in the medium and fluorescence microscopy by Sytox green. No toxic effects were observed in murine macrophage cell lines and Galleria mellonella larvae, suggesting fungal target selectivity. Therefore, peptide RQ18 represents a promising strategy as a dual antifungal and antibiofilm agent that contributes to infection control without damaging mammalian cells.


Subject(s)
Amphotericin B , Antifungal Agents , Animals , Mice , Antifungal Agents/pharmacology , Amphotericin B/pharmacology , Peptides/pharmacology , Candida tropicalis , Biofilms , Microbial Sensitivity Tests , Mammals
6.
Brain Sci ; 14(1)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38248286

ABSTRACT

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy.

7.
Int J Mol Sci ; 24(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37958572

ABSTRACT

Brazil has several important biomes holding impressive fauna and flora biodiversity. Cerrado being one of the richest ones and a significant area in the search for new plant-based products, such as foods, cosmetics, and medicines. The therapeutic potential of Cerrado plants has been described by several studies associating ethnopharmacological knowledge with phytochemical compounds and therapeutic effects. Based on this wide range of options, the Brazilian population has been using these medicinal plants (MP) for centuries for the treatment of various health conditions. Among these, we highlight metabolic diseases, namely obesity and its metabolic alterations from metabolic syndrome to later stages such as type 2 diabetes (T2D). Several studies have shown that adipose tissue (AT) dysfunction leads to proinflammatory cytokine secretion and impaired free fatty acid (FFA) oxidation and oxidative status, creating the basis for insulin resistance and glucose dysmetabolism. In this scenario, the great Brazilian biodiversity and a wide variety of phytochemical compounds make it an important candidate for the identification of pharmacological strategies for the treatment of these conditions. This review aimed to analyze and summarize the current literature on plants from the Brazilian Cerrado that have therapeutic activity against obesity and its metabolic conditions, reducing inflammation and oxidative stress.


Subject(s)
Diabetes Mellitus, Type 2 , Metabolic Diseases , Plants, Medicinal , Brazil , Ecosystem , Obesity/drug therapy , Phytochemicals/therapeutic use
8.
Cien Saude Colet ; 28(5): 1525-1538, 2023 May.
Article in Portuguese, English | MEDLINE | ID: mdl-37194884

ABSTRACT

The aim of the present study was to analyze the management organization of food and nutrition actions in the municipalities of Mato Grosso do Sul. This is a descriptive-exploratory study carried out in Mato Grosso do Sul, in which each municipal food and nutrition manager answered questions about performance, governance and financing profile. Data analysis applied frequency, chi-square test and decision tree tools. All cities were included (n=79). Most of the participants were female (92.4%), white (62%), nurses (45.6%) or nutritionists (36.7%). Financial management proved to be so incipient in the state since specific food and nutrition funding was neglected. The absence of a technical area in the municipality's organizational chart was consistent with the lack of knowledge of actions, goals and resource allocation. Their presence coincided with having formally appointed technical managers, municipal food and nutrition policy, goals and elaboration of specialized materials. The present study also proposed a decision tree pointing that having a nutritionist in the team led to a positive result. The failures found in this study partly clarify the causes of the unsettling situation in the state. Our findings can support the creation of intervention strategies.


Mato Grosso do Sul é líder nacional em mortes atribuíveis ao excesso de peso. O objetivo foi analisar a organização da gestão das ações da área de alimentação e nutrição dos municípios de MS. Estudo descritivo-exploratório realizado em MS, no qual cada gestor municipal de alimentação e nutrição respondeu sobre seu perfil, atuação, governança e financiamento. A análise de dados valeu-se de frequência, teste qui-quadrado e árvore de decisão. Todos participaram (n=79), a maioria era do sexo feminino (92,4%), raça/cor branca (62%), enfermeiros (45,6%) ou nutricionistas (36,7%). A gestão financeira mostrou-se tão incipiente no estado, que financiamentos específicos da área foram desprezados. A ausência de área técnica no organograma do município foi congruente com o desconhecimento de ações, metas e alocação de recursos; sua presença coincidiu com haver responsáveis técnicos formalmente indicados, política de alimentação e nutrição municipal, metas e elaboração de materiais. A árvore de decisão mostra que ter nutricionista na equipe traz efeitos positivos, como mais participação em processos decisórios. Falhas encontradas esclarecem, em parte, causas da grave situação do estado, e podem apoiar a criação de estratégias de intervenção.


Subject(s)
Nutritional Status , Organizations , Humans , Brazil , Cities , Decision Making
9.
Ciênc. Saúde Colet. (Impr.) ; 28(5): 1525-1538, maio 2023. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1439802

ABSTRACT

Resumo Mato Grosso do Sul é líder nacional em mortes atribuíveis ao excesso de peso. O objetivo foi analisar a organização da gestão das ações da área de alimentação e nutrição dos municípios de MS. Estudo descritivo-exploratório realizado em MS, no qual cada gestor municipal de alimentação e nutrição respondeu sobre seu perfil, atuação, governança e financiamento. A análise de dados valeu-se de frequência, teste qui-quadrado e árvore de decisão. Todos participaram (n=79), a maioria era do sexo feminino (92,4%), raça/cor branca (62%), enfermeiros (45,6%) ou nutricionistas (36,7%). A gestão financeira mostrou-se tão incipiente no estado, que financiamentos específicos da área foram desprezados. A ausência de área técnica no organograma do município foi congruente com o desconhecimento de ações, metas e alocação de recursos; sua presença coincidiu com haver responsáveis técnicos formalmente indicados, política de alimentação e nutrição municipal, metas e elaboração de materiais. A árvore de decisão mostra que ter nutricionista na equipe traz efeitos positivos, como mais participação em processos decisórios. Falhas encontradas esclarecem, em parte, causas da grave situação do estado, e podem apoiar a criação de estratégias de intervenção.


Abstract The aim of the present study was to analyze the management organization of food and nutrition actions in the municipalities of Mato Grosso do Sul. This is a descriptive-exploratory study carried out in Mato Grosso do Sul, in which each municipal food and nutrition manager answered questions about performance, governance and financing profile. Data analysis applied frequency, chi-square test and decision tree tools. All cities were included (n=79). Most of the participants were female (92.4%), white (62%), nurses (45.6%) or nutritionists (36.7%). Financial management proved to be so incipient in the state since specific food and nutrition funding was neglected. The absence of a technical area in the municipality's organizational chart was consistent with the lack of knowledge of actions, goals and resource allocation. Their presence coincided with having formally appointed technical managers, municipal food and nutrition policy, goals and elaboration of specialized materials. The present study also proposed a decision tree pointing that having a nutritionist in the team led to a positive result. The failures found in this study partly clarify the causes of the unsettling situation in the state. Our findings can support the creation of intervention strategies.

10.
Molecules ; 28(2)2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36677949

ABSTRACT

Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.


Subject(s)
Antineoplastic Agents , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid , Humans , Apoptosis , Oxidative Stress , Antineoplastic Agents/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Cell Proliferation , Cellular Senescence , Pyridines/pharmacology , K562 Cells
11.
Toxins (Basel) ; 15(1)2023 01 05.
Article in English | MEDLINE | ID: mdl-36668862

ABSTRACT

In recent years, antimicrobial peptides isolated from amphibian toxins have gained attention as new multifunctional drugs interacting with different molecular targets. We aimed to rationally design a new peptide from temporin-PTa. Hp-MAP3 (NH2-LLKKVLALLKKVL-COOH), net charge (+4), hydrophobicity (0.69), the content of hydrophobic residues (69%), and hydrophobic moment (0.73). For the construction of the analog peptide, the physicochemical characteristics were reorganized into hydrophilic and hydrophobic residues with the addition of lysines and leucines. The minimum inhibitory concentration was 2.7 to 43 µM against the growth of Gram-negative and positive bacteria, and the potential for biofilm eradication was 173.2 µM. Within 20 min, the peptide Hp-MAP3 (10.8 µM) prompted 100% of the damage to E. coli cells. At 43.3 µM, eliminated 100% of S. aureus within 5 min. The effects against yeast species of the Candida genus ranged from 5.4 to 86.6 µM. Hp-MAP3 presents cytotoxic activity against tumor HeLa at a concentration of 21.6 µM with an IC50 of 10.4 µM. Furthermore, the peptide showed hemolytic activity against murine erythrocytes. Structural studies carried out by circular dichroism showed that Hp-MAP3, while in the presence of 50% trifluoroethanol or SDS, an α-helix secondary structure. Finally, Amphipathic Hp-MAP3 building an important model for the design of new multifunctional molecules.


Subject(s)
Amphibian Proteins , Antimicrobial Cationic Peptides , Animals , Humans , Mice , Amino Acid Sequence , Amphibian Proteins/chemistry , Amphibian Proteins/pharmacology , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Circular Dichroism , Escherichia coli/drug effects , Microbial Sensitivity Tests , Ranidae , Staphylococcus aureus/drug effects
12.
Toxins (Basel) ; 14(10)2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36287965

ABSTRACT

The importance of neuroinflammation in neurology is becoming increasingly apparent. In addition to neuroinflammatory diseases such as multiple sclerosis, the role of neuroinflammation has been identified in many non-inflammatory neurological disorders such as stroke, epilepsy, and cancer. The immune response within the brain involves the presence of CNS resident cells; mainly glial cells, such as microglia, the CNS resident macrophages. We evaluated the peptide Ca-MAP1 bioinspired on the C. albicans immature cytolytic toxin candidalysin to develop a less hemolytic peptide with anti-neuroinflammatory, antibacterial, and cytotoxic activity against tumor cells. In silico and in vitro studies were performed at various concentrations. Ca-MAP1 exhibits low hemolytic activity at lower concentrations and was not cytotoxic to MRC-5 and BV-2 cells. Ca-MAP1 showed activity against Acinetobacter baumannii, Escherichia coli ATCC, E. coli KPC, Klebsiella pneumoniae ATCC, Pseudomonas aeruginosa, and Staphylococcus aureus ATCC. Furthermore, Ca-MAP1 exhibits anti-neuroinflammatory activity in the BV-2 microglia model, with 93.78% inhibition of nitrate production at 18.1 µM. Ca-MAP1 presents cytotoxic activity against tumor cell line NCI-H292 at 36.3 µM, with an IC50 of 38.4 µM. Ca-MAP1 demonstrates results that qualify it to be evaluated in the next steps to promote the control of infections and provide an alternative antitumor therapy.


Subject(s)
Escherichia coli , Mycotoxins , Mycotoxins/toxicity , Mycotoxins/metabolism , Nitrates/metabolism , Candida albicans , Anti-Bacterial Agents/chemistry , Peptides/chemistry , Pseudomonas aeruginosa , Microbial Sensitivity Tests
13.
Biochim Biophys Acta Gen Subj ; 1866(12): 130244, 2022 12.
Article in English | MEDLINE | ID: mdl-36162730

ABSTRACT

Antimicrobial peptides (AMPs) are promising tools for developing new antibiotics. We described the design of IKR18, an AMP designed with the aid of computational tools. IKR18 showed antimicrobial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). CD studies revealed that IKR18 assumes an alpha-helical structure in the membrane-mimetic environment. The action mechanism IKR18 involves damage to the bacteria membrane, as demonstrated by Sytox green uptake. Furthermore, IKR18 displayed synergic and additive effects in combination with antibiotics ciprofloxacin and vancomycin. The peptide showed anti-biofilm activity in concentration and efficiency compared with commercial antibiotics, involving the direct death of bacteria, as confirmed by scanning electron microscopy. The anti-infective activity of IKR18 was demonstrated in the Galleria mellonella model infected with S. aureus, MRSA, and Acinetobacter baumannii. The novel bioinspired peptide, IKR18, proved to be effective in the control of bacterial infection, opening opportunities for the development of further assays, including preclinical models.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Moths , Animals , Antimicrobial Peptides , Staphylococcus aureus , Microbial Sensitivity Tests , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria
14.
Microb Pathog ; 172: 105791, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36150557

ABSTRACT

This study investigated the antimicrobial and antibiofilm activity of KWI18, a new synthetic peptide. KWI18 was tested against planktonic cells and Pseudomonas aeruginosa and Candida parapsilosis biofilms. Time-kill and synergism assays were performed. Sorbitol, ergosterol, lipid peroxidation, and protein oxidation assays were used to gain insight into the mechanism of action of the peptide. Toxicity was evaluated against erythrocytes and Galleria mellonella. KWI18 showed antimicrobial activity, with minimum inhibitory concentration (MIC) values ranging from 0.5 to 10 µM. KWI18 at 10 × MIC reduced P. aeruginosa and C. parapsilosis biofilm formation and cell viability. Time-kill assays revealed that KWI18 inhibited the growth of P. aeruginosa in 4 h and that of C. parapsilosis in 6 h. The mechanism of action was related to ergosterol as well as induction of oxidative damage in cells and biofilms. Furthermore, KWI18 demonstrated low toxicity to erythrocytes and G. mellonella. KWI18 proved to be an effective antibiofilm agent, opening opportunities for the development of new antimicrobials.


Subject(s)
Anti-Infective Agents , Antimicrobial Peptides , Biofilms , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Hospitals , Ergosterol/pharmacology , Sorbitol/pharmacology
15.
Pharmaceuticals (Basel) ; 15(6)2022 Jun 07.
Article in English | MEDLINE | ID: mdl-35745643

ABSTRACT

Nature presents a wide range of biomolecules with pharmacological potential, including venomous animal proteins. Among the protein components from snake venoms, phospholipases (PLA2) are of great importance for the development of new anticancer compounds. Thus, we aimed to evaluate the PLA2 anticancer properties from Bothrops moojeni venom. The crude venom was purified through three chromatographic steps, monitored by enzymatic activity and SDS-PAGE (12%). The purified PLA2 denominated BmPLA2 had its molecular mass and N-terminal sequence identified by mass spectrometry and Edman degradation, respectively. BmPLA2 was assayed against human epithelial colorectal adenocarcinoma cells (Caco-2), human rhabdomyosarcoma cells (RD) and mucoepidermoid carcinoma of the lung (NCI-H292), using human fibroblast cells (MRC-5) and microglia cells (BV-2) as a cytotoxicity control. BmPLA2 presented 13,836 Da and a 24 amino acid-residue homologue with snake PLA2, which showed a 90% similarity with other Bothrops moojeni PLA2. BmPLA2 displayed an IC50 of 0.6 µM against Caco-2, and demonstrated a selectivity index of 1.85 (compared to MRC-5) and 6.33 (compared to BV-2), supporting its selectivity for cancer cells. In conclusion, we describe a new acidic phospholipase, which showed antitumor activity and is a potential candidate in the development of new biotechnological tools.

16.
Biomed Pharmacother ; 144: 112198, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34656058

ABSTRACT

Erythrina poeppigiana belongs to Fabaceae family (subfamily Papillionoideae) and is commonly found in tropical and subtropical regions in Brazil. Herein, we described the purification and characterization of a new Kunitz-type inhibitor, obtained from E. poeppigiana seeds (EpTI). EpTI is composed by three isoforms of identical amino-terminal sequences with a molecular weight ranging from 17 to 20 kDa. The physicochemical features showed by EpTI are common to Kunitz inhibitors, including the dissociation constant (13.1 nM), stability against thermal (37-100 °C) and pH (2-10) ranging, and the presence of disulfide bonds stabilizing its reactive site. Furthermore, we investigated the antimicrobial, anti-adhesion, and anti-biofilm properties of EpTI against Gram-positive and negative bacteria. The inhibitor showed antimicrobial activity with a minimum inhibitory concentration (MIC, 5-10 µM) and minimum bactericidal concentration (MBC) of 10 µM for Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Staphylococcus aureus, and Staphylococcus haemolyticus. The combination of EpTI with ciprofloxacin showed a marked synergistic effect, reducing the antibiotic concentration by 150%. The increase in crystal violet uptake for S. aureus and K. pneumoniae strains was approximately 30% and 50%, respectively, suggesting that the bacteria plasma membrane is targeted by EpTI. Treatment with EpTI at 1x and 10 x MIC significantly reduced the biofilm formation and prompted the disruption of a mature biofilm. At MIC/2, EpTI decreased the bacterial adhesion to polystyrene surface within 2 h. Finally, EpTI showed low toxicity in animal model Galleria mellonella. Given its antimicrobial and anti-biofilm properties, the EpTI sequence might be used to design novel drug prototypes.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Biofilms/drug effects , Erythrina , Plant Extracts/pharmacology , Trypsin Inhibitors/pharmacology , Animals , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/toxicity , Bacteria/growth & development , Biofilms/growth & development , Ciprofloxacin/pharmacology , Drug Synergism , Erythrina/chemistry , Microbial Sensitivity Tests , Moths/drug effects , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Seeds , Trypsin Inhibitors/isolation & purification , Trypsin Inhibitors/toxicity
17.
Biochim Biophys Acta Gen Subj ; 1865(9): 129937, 2021 09.
Article in English | MEDLINE | ID: mdl-34052310

ABSTRACT

BACKGROUND: Antimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus. METHODS: A physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations. RESULTS: RQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces. CONCLUSIONS: RQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application. GENERAL SIGNIFICANCE: These results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Cholesterol/pharmacology , Phospholipids/pharmacology , Pore Forming Cytotoxic Proteins/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Candida/drug effects , Cholesterol/chemistry , Escherichia coli/drug effects , Eukaryotic Cells/drug effects , Humans , Microbial Sensitivity Tests , Molecular Dynamics Simulation , Phospholipids/chemistry , Pore Forming Cytotoxic Proteins/chemical synthesis , Pore Forming Cytotoxic Proteins/chemistry , Staphylococcus/drug effects
18.
J Med Food ; 24(10): 1068-1075, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33872073

ABSTRACT

Acrocomia aculeata fruits are rich in monounsaturated fatty acid, ß-carotene, tocopherol, and other antioxidant compounds. The aim of our study was to investigate and compare the protective effects of A. aculeata pulp oil and microencapsulated pulp oil on brain oxidative damage induced by chronic restraint stress (CRS) in rats (cortex, hippocampus, and striatum). Thirty-six Wistar rats were divided into six treatment groups: C, P, and M groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively. The SC, SP, and SM groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively, and were then subjected to uninterrupted 6 h of CRS. After 21 days of testing, the rats were euthanized and the brain tissue of the groups was removed for evaluation for oxidative damage markers and antioxidant enzymes. Endpoints of oxidative stress (OS) markers (lipid peroxidation, protein carbonylation, and reduced glutathione [GSH]) and antioxidant enzymes (superoxide dismutase and catalase) were evaluated. By imposing chronic stress on rats, pulp oil and microcapsules of pulp oil induced positive antioxidant responses, mainly by increasing the GSH content, increasing the ability of neural tissues to deal with inherent OS, thus protecting against neurodegenerative diseases. The administration of A. aculeata pulp oil and microencapsulated pulp oil made the reversal of the oxidant parameters, which may protect the brain tissue of rats altered by CRS. The Clinical Trial Registration number: n° 1.008/2018 CEUA/UFMS.


Subject(s)
Arecaceae , Neuroprotective Agents , Animals , Antioxidants , Capsules , Rats , Rats, Wistar
19.
PLoS One ; 16(4): e0249919, 2021.
Article in English | MEDLINE | ID: mdl-33914744

ABSTRACT

Zootherapy is a traditional secular practice among the Guarani-Kaiowá indigenous ethnic group living in Mato Grosso do Sul, Brazil. My people use the oil extracted from larvae of the snout beetle Rhynchophorus palmarum (Linnaeus, 1758) to treat and heal skin wounds and respiratory diseases. Based on this ethnopharmacological knowledge, the chemical composition and antioxidant, antimicrobial, and healing properties of R. palmarum larvae oil (RPLO) were investigated, as well as possible toxic effects, through in vitro and in vivo assays. The chemical composition of the RPLO was determined using gas chromatography coupled with mass spectrometry. The antioxidant activity of RPLO was investigated through the direct 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and the antimicrobial activity was evaluated against Gram-positive and Gram-negative bacteria that are pathogenic to humans. The healing properties of RPLO were investigated by performing a cell migration assay using human lung fibroblasts (MRC-5), and the toxicity was analyzed, in vivo, using a Caenorhabditis elegans model and MRC-5 cells, in vitro. RPLO contains 52.2% saturated fatty acids and 47.4% unsaturated fatty acids, with palmitic acid (42.7%) and oleic acid (40%) representing its major components, respectively. RPLO possesses direct antioxidant activity, with a half-maximal inhibitory concentration (IC50) of 46.15 mg.ml-1. The antimicrobial activity of RPLO was not observed at a concentration of 1% (v/v). RPLO did not alter the viability of MRC-5 cells and did not exert toxic effects on C. elegans. Furthermore, MRC-5 cells incubated with 0.5% RPLO showed a higher rate of cell migration than that of the control group, supporting its healing properties. Taken together, RPLO possesses direct antioxidant activity and the potential to aid in the healing process and is not toxic toward in vitro and in vivo models, corroborating the safe use of the oil in traditional Guarani-Kaiowá medicine.


Subject(s)
Coleoptera/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Oils, Volatile/pharmacology , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Antioxidants/chemistry , Caenorhabditis elegans/drug effects , Cell Line , Cell Movement/drug effects , Cell Survival/drug effects , Coleoptera/growth & development , Gas Chromatography-Mass Spectrometry , Humans , Larva/chemistry , Larva/metabolism , Microbial Sensitivity Tests , Oils, Volatile/analysis , Oils, Volatile/chemistry
20.
J Anim Physiol Anim Nutr (Berl) ; 105(2): 364-375, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33226712

ABSTRACT

Metabolic syndrome (MetS) and obesity are growing in many parts of the world, becoming public health problems. It is proposed that foods with functional properties can assist in the treatment of these diseases. Crude buriti pulp oil (BPO) is a food traditionally consumed by residents in the Pantanal, Cerrado and Brazilian Amazon. It is rich in oleic acid, tocopherols and carotenoids, emerging as a potential functional food. Thus, this study aimed to evaluate the effect of the supplementation of BPO on metabolic disorders caused by a high-fat diet. Four groups of C57BL6 mice were used, a lean group with AIN-93M diet and control oil supplementation, an obese group with a high-fat diet and control oil supplementation, and two obese groups with a high-fat diet and BPO supplementation in the amounts of 50 and 100 mg/kg. BPO worsened the metabolic state caused by the high-fat diet, worsening risk factors associated with MetS, as the abdominal circumference and retroperitoneal fat, serum levels of total cholesterol, uric acid, alanine transaminase, glucose and triglycerides, and renal fat, in addition to changes in glycaemic control and oxidative stress markers. C57BL/6 mice fed with a high-fat diet and supplemented with BPO presented a worsening in metabolic risk factors associated with MetS.


Subject(s)
Metabolic Diseases , Rodent Diseases , Animals , Carotenoids , Diet, High-Fat/adverse effects , Liver , Metabolic Diseases/veterinary , Mice , Mice, Inbred C57BL
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