RESUMO

This study aims to investigate the essential oil from leaves of Eugenia pohliana (EOEP) in regard to its chemical composition, antimicrobial and drug-enhancing activity, as well as the reduction of fungal virulence capacity. Chemical characterization using GC-MS showed as major components the sesquiterpenes δ-cadinene, Epi-α-Muurolol, and bicyclogermacrene. The results of antibacterial tests indicated that Staphylococcus aureus was more sensitive to EOEP, that also enhanced the efficacy of gentamicin, erythromycin, and norfloxacin. EOEP exhibited antifungal properties against Candida albicans, in addition to potentiating the effectiveness of fluconazole against Candida tropicalis. It showed anti-virulence effects in all fungal strains. These findings underscore E. pohliana as a potential candidate for the prospection of novel therapeutic agents to treat infectious diseases caused by resistant microbes.

RESUMO

Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.

Assuntos

Antibacterianos , Proteínas de Bactérias , Permeabilidade da Membrana Celular , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Tiazinas/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética

RESUMO

This study investigated crotamine (CTA), a peptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, known for its exceptional cell penetration potential. The objective was to explore the antibacterial and antifungal activity of CTA, its ability to inhibit efflux pumps and evaluate the effectiveness of its pharmacological combination with antibiotics and antifungals. In microbiological assays, CTA in combination with antibiotics was tested against strains of S. aureus and the inhibition of NorA, Tet(K) and MepA efflux pumps was also evaluated. CTA alone did not present clinically relevant direct antibacterial action, presenting MIC > 209.7 µM against strains S. aureus 1199B, IS-58, K2068. The standard efflux pump inhibitor CCCP showed significant effects in all negative relationships to assay reproducibility. Against the S. aureus 1199B strain, CTA (20.5 µM) associated with norfloxacin diluted 10 × (320.67 µM) showed a potentiating effect, in relation to the control. Against the S. aureus IS-58 strain, the CTA associated with tetracycline did not show a significant combinatorial effect, either with 2304 or 230.4 µM tetracycline. CTA at a concentration of 2.05 µM associated with ciprofloxacin at a concentration of 309.4 µM showed a significant potentiating effect. In association with EtBr, CTA at concentrations of 2.05 and 20.5 µM potentiated the effect in all strains tested, reducing the prevention of NorA, Tet(K) and MepA efflux pumps. In the C. albicans strain, a potentiating effect of fluconazole (334.3 µM) was observed when combined with CTA (2.05 µM). Against the C. tropicalis strain, a significant effect was also observed in the association of fluconazole 334.3 µM, where CTA 2.05 µM considerably reduced fungal growth and decreased the potentiation of fluconazole. Against the C. krusei strain, no significant potentiating effect of fluconazole was obtained by CTA. Our results indicate that CTA in pharmacological combination potentiates the effects of antibiotics and antifungal. This represents a new and promising antimicrobial strategy for treating a wide variety of infections.

Assuntos

Antibacterianos , Antifúngicos , Venenos de Crotalídeos , Crotalus , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Antifúngicos/química , Antibacterianos/farmacologia , Venenos de Crotalídeos/farmacologia , Animais , Staphylococcus aureus/efeitos dos fármacos , Sinergismo Farmacológico , Candida albicans/efeitos dos fármacos , Serpentes Peçonhentas

RESUMO

To assess the antibacterial effectiveness of Lippia macrophylla essential oil (LMEO) against multidrug-resistant Acinetobacter baumannii isolates, both as a standalone treatment and in combination with conventional antibiotics. LMEO demonstrated a significant inhibitory effect on the growth of A. baumannii, with a minimum inhibitory concentration (MIC) below 500 µg/mL. Notably, LMEO was capable of reversing the antibiotic resistance of clinical isolates or reducing their MIC values when used in combination with antibiotics, showing synergistic (FICI≤0.5) or additive effects. The combination of LMEO and imipenem was particularly effective, displaying synergistic interactions for most isolates. Ultrastructural analyses supported these findings, revealing that the combination of LMEO+ceftazidime compromised the membrane integrity of the Acb35 isolate, leading to cytoplasmic leakage and increased formation of Outer Membrane Vesicles (OMVs). Taken together our results point for the use of LMEO alone or in combination as an antibacterial agent against A. baumannii. These findings offer promising avenues for utilizing LMEO as a novel antibacterial strategy against drug-resistant infections in healthcare settings, underscoring the potential of essential oils in enhancing antibiotic efficacy.

Assuntos

Acinetobacter baumannii , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Lippia , Testes de Sensibilidade Microbiana , Óleos Voláteis , Acinetobacter baumannii/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Lippia/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Relação Dose-Resposta a Droga

RESUMO

Neuropathic pain is a high-intensity pain that can be caused by compression, transection, injury, nerve infiltration and drug treatment of cancer. Furthermore, drug therapy has low clinical efficacy, many adverse effects and remission of painful symptoms. In this way, natural products derived from plants constitute a promising therapeutic alternative. Therefore, the aim of this study was to evaluate the antihyperalgesic effect of γ-terpinene (γ-TPN) e γ-terpinene in ß-cyclodextrin inclusion complexes (TPN/CD) on neuropathic pain induced by tumor cells. Complexation extended the effect time for another 5 h and daily treatment for six days with γ-TPN (50 mg/kg, p.o.) and γ-TPN/ß-CD (50 mg/kg, p.o.) significantly reduced (p < 0.001) the mechanical hyperalgesia induced by the administration of 2x106 sarcoma cells 180 in the around the sciatic nerve. In addition, the Grip and Rota-rod techniques demonstrated that there was no interference on the muscle strength and motor coordination of the animals, suggesting that the compound under study does not have central nervous system depressant effects at the doses used. Molecular docking studies demonstrate favorable binding energies between γ-TPN and ß-CD, and alpha-2 adrenergic, glutamatergic, opioid and cholinergic receptors. Thus, this study demonstrates the potential of terpinene complexation in controlling neuropathic pain induced by tumor cells.

Assuntos

Monoterpenos Cicloexânicos , Hiperalgesia , Monoterpenos , Neuralgia , beta-Ciclodextrinas , Animais , beta-Ciclodextrinas/química , beta-Ciclodextrinas/administração & dosagem , Neuralgia/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Masculino , Monoterpenos/farmacologia , Monoterpenos/química , Monoterpenos/administração & dosagem , Camundongos , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/administração & dosagem , Modelos Animais de Doenças , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Sarcoma 180/tratamento farmacológico , Sarcoma 180/patologia

RESUMO

The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.

Assuntos

Antipiréticos , Antitussígenos , Etanol , Expectorantes , Momordica charantia , Extratos Vegetais , Folhas de Planta , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Camundongos , Antitussígenos/farmacologia , Antitussígenos/química , Antitussígenos/isolamento & purificação , Folhas de Planta/química , Ratos , Etanol/química , Antipiréticos/farmacologia , Antipiréticos/química , Antipiréticos/isolamento & purificação , Masculino , Momordica charantia/química , Expectorantes/farmacologia , Expectorantes/isolamento & purificação , Expectorantes/química , Tosse/tratamento farmacológico , Ratos Wistar , Relação Dose-Resposta a Droga , Saccharomyces cerevisiae/efeitos dos fármacos , Febre/tratamento farmacológico

RESUMO

Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide-type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N-acetylglucosamine, CYP-51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP-51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus.

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Popularly known as "penicilina" and "terramicina", Alternanthera brasiliana (L.) Kuntze belongs to the Amaranthaceae family and stands out for its ethnomedicinal uses in the treatment of infections caused by pathogenic microorganisms in some countries. AIM OF THE STUDY: The present study aimed to carry out a literature review and analyze whether the scientific evidence really validates the numerous indications for the use of A. brasiliana in traditional medicine for the treatment of infectious diseases. Phytochemical and toxicological studies related to this species were also analyzed. MATERIAL AND METHODS: Scientific documents were retrieved from Google Scholar, PubMed®, ScienceDirect®, SciELO, SpringerLink®, Scopus®, and Web of Science™ databases. The literature was reviewed from the first report on the antimicrobial activity of A. brasiliana in 1994 until April 2024. RESULTS: According to the scientific documents analyzed, it was observed that A. brasiliana is widely used as a natural antibiotic for the treatment of infectious diseases in Brazil, mainly in the states of Rio Grande do Sul, Mato Grosso, and Minas Gerais. Its ethnomedicinal uses have also been reported in other countries such as Colombia and India. The leaves (78%) of A. brasiliana are the main parts used in the preparation of herbal medicines by traditional communities. Several A. brasiliana extracts showed low activity when evaluated against pathogens, including gram-positive bacteria, gram-negative bacteria, parasitic protozoa, and fungi. Only two studies reported that extracts from this plant showed high activity against the herpes simplex virus, Mycobacterium smegmatis, and Candida albicans. Phytochemicals belonging to the classes of phenolic compounds and flavonoid (52%), saturated and unsaturated fatty acids (33%), steroids and phytosterols (8%), terpenoids (5%), and fatty alcohol esters (2%) were identified in A. brasiliana. Toxicity (in vivo) and cytotoxicity (in vitro) studies of polar and non-polar extracts obtained from A. brasiliana leaves indicated that this plant is biologically safe. CONCLUSION: Despite being widely used as a natural antibiotic by traditional communities, scientific investigations related to the antimicrobial potential of A. brasiliana extracts have indicated inactivity against several pathogens.

Assuntos

Amaranthaceae , Medicina Tradicional , Compostos Fitoquímicos , Extratos Vegetais , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Amaranthaceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Animais , Doenças Transmissíveis/tratamento farmacológico , Etnofarmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Fitoterapia , Brasil

RESUMO

This study investigated the sediment geochemistry of a fish farming area in net cage tanks in the Rosário reservoir, Brazil. Three areas were investigated: reference (RA), fish farming (FFA), and dispersion (DA). The results were analyzed through correlation, similarity, principal component analysis, comparison with legislation, sediment quality guidelines, and sediment pollution indices. The mean concentrations for RA, FFA, and DA areas were respectively: Cu (mg.kg-1) 37.74, 62.23, and 71.83; Mn (mg.kg-1) 22.55, 66.48, and 55.90; Zn (mg.kg-1) 9.13, 114.83, and 94.27; Fe (%) 0.28, 0.40, and 0.43; OM (%) 15.84, 21.95, and 18.45; TOC (%) 1.86, 3.69, and 6.05; TN (mg.kg-1) 2365.00, 5015.00, and 3447.51; TP (mg.kg-1) 780.00, 6896.00, and 2585.50; ORP (mV) -95.50, -135.20, and -127.10; pH 6.60, 6.58, and 6.05; <63 µm 90.59, 78.68, and 87.30. Statistically, the influence of fish farming on sediment, organic matter, and pollutant sedimentation was demonstrated. Cu and Zn concentrations were below sediment quality guidelines. Regarding legal limits (resolution 454/2012/CONAMA), nutrients in the FFA area exceeded by 60% (TN) and 100% (TP), while in DA and RA areas they were 100% lower. TOC was 100% lower in all areas. Organic matter exceeded the limit by 100% in all areas. Pollution indices resulted in: low contamination factor 78%; unpolluted for 87% of pollution load and 83% of combined pollution; moderately polluted for 75% of the Nemerow index. The greatest impacts and influence of farming on pollutant sedimentation were more concentrated in the fish farming area. In terms of legal aspects and pollution indices, fish farming produced low levels of trace metal pollution and nutrient concentrations exceeded legal limits.

Assuntos

Aquicultura , Monitoramento Ambiental , Sedimentos Geológicos , Tilápia , Poluentes Químicos da Água , Brasil , Sedimentos Geológicos/análise , Sedimentos Geológicos/química , Animais , Poluentes Químicos da Água/análise

RESUMO

Fungal infections are a public health problem that mainly affects immunosuppressed people, Candida spp. have been responsible for most sources of contamination and invasive fungal infections described around the world. The need arises to find new therapeutic approaches to combat growing infections. Plants and natural products have been considered a valuable source for discovering new molecules with active ingredients. Diosgenin is a sapogenin found in the families of Leguminosae and Dioscoreaceae, it is obtained mainly from the dioscin saponin through the hydrolysis method, it is a phytochemical that has been highlighted in the treatment of various diseases, as well as in combating microbial resistance. The present study aimed to evaluate the susceptibility of fungal strains to diosgenin, as well as verify the association with the reference drug and evaluate the inhibition of the virulence factor through morphological changes in the yeast state to the filamentous form of hyphae and pseudohyphae in strains of Candida albicans, Candida tropicalis and Candida krusei using the broth microdilution method and microculture technique. Antifungal assays revealed that diosgenin was not able to inhibit the growth of the tested strains. However, it was able to inhibit the fungal dimorphism of the strains evaluated, however further studies are recommended to verify its effectiveness against other virulence factors.

Assuntos

Antifúngicos , Candida , Diosgenina , Testes de Sensibilidade Microbiana , Diosgenina/farmacologia , Diosgenina/química , Diosgenina/análogos & derivados , Antifúngicos/farmacologia , Antifúngicos/química , Candida/efeitos dos fármacos , Virulência/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade

RESUMO

Geopropolis resins are produced by stingless bees (Meliponinae), developed from the collection of resinous materials, waxes and exudates, from the flora of the region where stingless bees are present, in addition to the addition of clay or earth in its composition. Several biological activities are attributed to Ethanol Extracts of Geopropolis (EEGP). The bioactive properties are associated with the complex chemical composition that the samples have. This work aims to evaluate the biological activities of the EEGP, in order to contribute with a natural therapeutic alternative, to face infections, mainly those caused by resistant strains of Staphylococcus aureus. The EEGP MIC tests showed antibacterial activity against two strains of S. aureus, both at concentrations of 550 µg/mL. The MBC performed with the inhibition values showed that the EEGP has bacteriostatic activity in both strains. Biofilm inhibition rates exhibited an average value greater than 65 % at the highest concentration. The EEGP antioxidant potential test showed good antioxidant activity (IC50) of 11.05±1.55 µg/mL. In the cytotoxicity test against HaCat cells, after 24 hours, EEGP induced cell viability at the three tested concentrations (550 µg/mL: 81.68±3.79 %; 1100 µg/mL: 67.10±3.76 %; 2200 µg/mL: 67.40±1.86 %). In view of the above, the safe use of EEGP from the brazilian northeast could be proven by the cytotoxicity test, and its use as an antioxidant and antibacterial agent has proven to be effective, as an alternative in combating oxidative stress and microorganisms such as S. aureus, which, through the spread and ongoing evolution of drug resistance, generates an active search for effective solutions.

Assuntos

Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Animais , Abelhas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Humanos , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Própole/química , Própole/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a Droga

RESUMO

This study aimed to evaluate the antibacterial and inhibitory action of NorA, Tet(K), MsrA and MepA efflux pumps in S. aureus strains using the sesquiterpenes named trans-caryophyllene and caryophyllene oxide, both isolated and encapsulated in liposomes. The antibacterial and inhibitory action of these efflux pumps was evaluated through the serial microdilution test in 96-well microplates. Each sesquiterpene and liposome/sesquiterpene was combined with antibiotics and ethidium bromide (EtBr). The antibiotics named norfloxacin, tetracycline and erythromycin were used. The 1199 B, IS-58, RN4220 and K2068 S. aureus strains carrying NorA, Tet(K), MsrA and MepA, respectively, were tested. In the fluorescence measurement test, K2068 S. aureus was incubated with the sesquiterpenes and EtBr, and the fluorescence emission by EtBr was measured. The tested substances did not show direct antibacterial activity, with MIC >1024 µg/mL. Nonetheless, the isolated trans-caryophyllene and caryophyllene oxide reduced the MIC of antibiotics and EtBr, indicating inhibition of NorA, Tet(K) and MsrA. In the fluorescence test, these same sesquiterpenes increased fluorescence emission, indicating inhibition of MepA. Therefore, the sesquiterpenes named trans-caryophyllene and caryophyllene oxide did not show direct antibacterial action; however, in their isolated form, they showed possible inhibitory action on NorA, Tet(K), MsrA and MepA efflux pumps. They may also act in antibiotic potentiation. Further studies are needed to identify the mechanisms involved in antibiotic potentiation and efflux pump inhibitory action.

Assuntos

Lipossomos , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Sesquiterpenos Policíclicos , Etídio , Proteínas de Bactérias/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos

RESUMO

BACKGROUND: Endotoxemia is a severe and dangerous clinical syndrome that results in elevated morbidity, especially in intensive care units. Neonates are particularly susceptible to endotoxemia due to their immature immune systems. There are few effective treatments for neonatal endotoxemia. One group of compounds with potential in the treatment of neonatal inflammatory diseases such as endotoxemia is the flavonoids, mainly due to their antioxidant and anti-inflammatory properties. Among these, naringenin (NGN) is a citrus flavonoid which has already been reported to have anti-inflammatory, antioxidant, anti-nociceptive and anti-cancer effects. Unfortunately, its clinical application is limited by its low solubility and bioavailability. However, cyclodextrins (CDs) have been widely used to improve the solubility of nonpolar drugs and enhance the bioavailability of these natural products. OBJECTIVE: We, therefore, aimed to investigate the effects of NGN non-complexed and complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) on neonatal endotoxemia injuries in a rodent model and describe the probable molecular mechanisms involved in NGN activities. METHOD: We used exposure to a bacterial lipopolysaccharide (LPS) to induce neonatal endotoxemia in the mice. RESULTS: It was found that NGN (100 mg/kg i.p.) exposure during the neonatal period reduced leukocyte migration and decreased pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) levels in the lungs, heart, kidneys or cerebral cortex. In addition, NGN upregulated IL-10 production in the lungs and kidneys of neonate mice. The administration of NGN also enhanced antioxidant enzyme catalase and SOD activity, reduced lipid peroxidation and protein carbonylation and increased the reduced sulfhydryl groups in an organ-dependent manner, attenuating the oxidative damage caused by LPS exposure. NGN decreased ERK1/2, p38MAPK and COX-2 activation in the lungs of neonate mice. Moreover, NGN complexed with HPßCD was able to increase the animal survival rate. CONCLUSION: NGN attenuated inflammatory and oxidative damage in the lungs, heart and kidneys caused by neonatal endotoxemia through the MAPK signaling pathways regulation. Our results show that NGN has beneficial effects against neonatal endotoxemia and could be useful in the treatment of neonatal inflammatory injuries.

Assuntos

Citrus , Endotoxemia , Flavanonas , Camundongos , Animais , Flavonoides/uso terapêutico , 2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Endotoxemia/induzido quimicamente , Endotoxemia/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Anti-Inflamatórios/farmacologia

RESUMO

The present article aims to evaluate the antifungal and antivirulence effect of the phytoconstituent Limonene against Candida spp. Antifungal assays were performed, where the concentration capable of inhibiting 50 % of fungal growth, the growth inhibition curve, the minimum fungicidal concentration, the evaluation of the modifying effect with fluconazole, the inhibitory effect of the substances on the morphological transition of Candida spp. and the statistical analysis of the results were determined. With this study, it was seen that limonene demonstrated growth inhibition for the strains tested and when associated the natural compound with Fluconazole, there was potentiation of the effect of the drug, since the inhibition of growth by the combination occurred at lower concentrations against all strains tested, when compared to the drug alone, which inhibited growth at the highest concentration. In the test to determine the Minimum Fungicidal Concentration of the products tested alone and in combination, it was found that in the case of Candida strains, growth inhibition by limonene occurred at a concentration of 1024 µg/mL. For Fluconazole, growth impairment ranged from > 1024 µg/mL to 256 µg/mL for the strains. And when combined, limonene potentiated the action of FCZ, making fungal colonization unfeasible at concentrations below 1024 µg/mL. Regarding the morphological transition from yeast to hyphae, limonene was used at concentrations of 1024 µg/mL and 512 µg/mL, and it was found that, for CA and CK, the filaments were reduced in number and size at the highest concentration and against CT, the morphological transition from yeast to hyphae/pseudohyphae was totally inhibited, and if compared to the growth control, limonene was able to reduce fungal growth at concentrations greater than 512 µg/mL. This compound has antimicrobial activity described, due to its ability to interfere in the gene expression of the fungus, the limited therapeutic options and the recent emergence of multidrug-resistant Candida species represent a significant challenge for human medicine and highlight the need for new therapeutic approaches, and in this study a great potential of limonene was revealed in relation to the perspective of increasing the efficiency of commercial drug. This work can bring an important contribution to the scientific database, while emphasizing that in-depth studies and tests on the subject, in order to better investigate its effectiveness and mechanisms by which they exert their effects, are still necessary.

Assuntos

Antifúngicos , Candida , Humanos , Antifúngicos/farmacologia , Fluconazol/farmacologia , Limoneno/farmacologia , Saccharomyces cerevisiae , Virulência , Fungos , Testes de Sensibilidade Microbiana

RESUMO

Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents. In this context, this study aimed to evaluate the potential of the BC in the treatment alcohol withdrawal-induced anxiety in adult zebrafish (aZF). Initially, BC was submitted to antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl radical. Subsequently, the aZF (n = 6/group) were treated with BC (0.1 or 1 or 10 mg/mL; 20 µL; p.o.), and the sedative effect and acute toxicity (96 h) were evaluated. Then, the anxiolytic-like effect and the possible GABAergic mechanism were analyzed through the Light & Dark Test. Finally, BC action was evaluated for treating alcohol withdrawal-induced anxiety in aZF. Molecular docking was performed to evaluate the interaction of the major chemical constituents of BC with the GABAA receptor. BC showed antioxidant potential, a sedative effect, was not toxic, and all doses of BC had an anxiolytic-like effect and showed potential for the treatment of alcohol withdrawal-induced anxiety in aZF. In addition to the anxiolytic action, the main chemical constituents of BC were confirmed in the molecular docking, thus suggesting that BC is an anxiolytic that modulates the GABAergic system and has pharmacological potential for the treatment of alcohol withdrawal-induced anxiety.

Assuntos

Alcoolismo , Ansiolíticos , Síndrome de Abstinência a Substâncias , Animais , Peixe-Zebra/fisiologia , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Alcoolismo/tratamento farmacológico , Simulação de Acoplamento Molecular , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Receptores de GABA-A , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Suplementos Nutricionais , Hipnóticos e Sedativos

RESUMO

Biofilms are a bacterial resistance strategy through which microorganisms organize themselves in the form of a colony fixed to a surface that is protected by a polymer matrix. Infectious diseases that result in biofilm formation have been considered a relevant public health problem due to the potential to increase patient morbidity and mortality, in addition to increasing the burden on health services. Such pathologies are treated with the use of antimicrobial drugs, the indiscriminate use of which has contributed to the process of bacterial resistance, demanding the need to invest in new alternatives to combat them. Based on this, the present work aimed to evaluate the anti-biofilm formation and eradication capacity of Hecogenin Acetate, a steroidal sapogenin of natural origin with important antibacterial properties. For this, we used strains of Streptococcus mutans INCQS 00,446 (ATCC 25,175), Enterococcus faecalis INCQS 00,018 (ATCC 14,506), Staphylococcus epidermidis INCQS 00,016 (ATCC 12,228), Staphylococcus aureus ATCC 25,923, Pseudomonas aeruginosa ATCC 9027 and Escherichia coli ATCC 259,223. The formation, formation inhibition and treatment assays were carried out in microdilution plates and revealed using the crystal violet method. Readings were carried out using absorbance at wavelengths of 492 nm. All tests were performed in triplicate and statistical analyzes were performed using Graphpad Prism v.5.0 software. It was observed that the bacterial strains used have a relevant capacity for biofilm formation, with the Gram positive ones identified in the present study as the best former. In the results of the analyzes with bacterial biofilm, it was identified that Hecogenin Acetate had a relevant antibiofilm capacity, and could therefore serve as a basis for further research into the development of new antimicrobial drugs.

Assuntos

Anti-Infecciosos , Compostos de Espiro , Esteroides , Humanos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias , Biofilmes , Testes de Sensibilidade Microbiana

RESUMO

Stingless bees belong to the Meliponini tribe and are widely distributed in the tropics and subtropics, where they perform important ecological services. Among the best distributed groups of stingless bees is the genus Scaptotrigona, which includes 22 species distributed throughout the neotropical region, including the area from Mexico to Argentina. Bees of this genus are responsible for the production of products such as honey, propolis, geopropolis and fermented pollen ("saburá"). This review aimed to provide an overview of the chemical composition and biological activities associated with derived products from stingless bees of the genus Scaptotrigona. The bibliographic review was carried out through searches in the Scopus, Web of Science, ScienceDirect and PubMed databases, including publications from 2003 to January 2023. The study of the chemodiversity of products derived from Scaptotrigona demonstrated the mainly presence of flavonoids, phenolic acids, terpenoids and alkaloids. It was also demonstrated that products derived from bees of the genus Scaptotrigona exhibit a wide range of biological effects, such as antibacterial, antioxidant, anti-inflammatory and antifungal activities, among other bioactivities. This review provides an overview of phytochemical and pharmacological investigations of the genus Scaptotrigona. However, it is essential to clarify the toxicity and food safety of these products.

Assuntos

Mel , Himenópteros , Própole , Animais , Antibacterianos/farmacologia , Abelhas , México , Própole/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Hidroxibenzoatos/química , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia

RESUMO

Objectives: This study aimed to analyze the knowledge of dental surgeons concerning the pharmacological effects of bisphosphonates (BP) and their impact on the health of patients undergoing oral surgery treatment. Materials and methods: A quantitative study was conducted with professionals in the Cariri region of Ceará, Brazil. The data were collected using a semi-structured questionnaire to interview the dental surgeons who met the inclusion criteria. The data were analyzed by Chi-square and Fischer's Exact tests using the SPSS program version 22.0. Results: The results indicated that most interviewed subjects have no experience with the dental treatment of individuals under treatment with bisphosphonates. When a sample of the medication was presented, a significant number of the participants (65.3%) did not recognize the drug. Among those who recognized it, 66.5% did not know how to treat bisphosphonate-using patients in the clinical routine. However, 95.1% of the professionals who recognized the need to discontinue these drugs admitted contacting the prescriber to establish the best dental conduct. Our results also showed that recently graduated professionals better understood the need to stop BP use before invasive treatment, although they did not know the protocol. Conclusion: In conclusion, a better knowledge of the pharmacological effects of BP is crucial for conducting adequate anamnesis, requesting additional tests, and performing medical monitoring, which has a significant impact on the clinical practice of dental surgeons.

RESUMO

Wound healing is a natural regenerative response to tissue injury and the conventional treatments consists of the use wound dressings with local administration of medicines, but, in some cases, are only partially effective and limited by toxicity or ineffective anti-microbial protection. Medicinal plants such as Lippia sidoides and Myracrodruon urundeuva have shown interesting pharmacological activities, allied to this, the association of these medicinal plants and nanotechnology, could mean an advantage in relation to classical approach. This study investigated the effect of a nanogel loaded with Lippia sidoides essential oil and Myracrodruon urundeuva extract (NAA) in an excisional wound healing model in rats. Animals were anesthetized and skin wounds were made using a metal punch. The groups were treated with vehicle, NAA or collagenase gel, for 7, 14 or 21 days and then sacrificed for tissue analysis. NAA did not show acute dermal irritation, further significantly reduced (p<0.05) the final wound area, accelerated the wound contraction and organization of collagen in the group treated for 14 days. The data presented here demonstrate the therapeutic potential for the use of nanotechnology associated with medicinal plants and provides evidence that corroborate with the use of L. sidoides and M. urundeuva as healing medicinal plants.

Assuntos

Lippia , Óleos Voláteis , Plantas Medicinais , Polietilenoglicóis , Polietilenoimina , Ratos , Animais , Nanogéis , Cicatrização , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico

RESUMO

The fixed oil from the inner mesocarp of Caryocar coriaceum Wittm. is used in the Chapada do Araripe region of Brazil for the treatment of genitourinary candidiasis. This study aimed to evaluate the chemical composition, antifungal activity, reduction of fungal virulence, and the preliminary toxicity of the fixed oil from the inner mesocarp of C. coriaceum tested against three Candida yeasts. The oil was characterized by gas chromatography (GC-MS and GC-FID). Antifungal activity was assessed using the serial microdilution method. Additionally, the potential of the oil as an enhancer of fluconazole action was tested at sub-inhibitory concentrations (MIC/8). The mechanism of action of C. coriaceum fixed oil was determined by evaluating the inhibition of morphological transition in Candida spp. The chemical composition of the fixed oil of C. coriaceum comprised both unsaturated and saturated fatty acids. Oleic (61 %) and palmitic (33 %) acids were the major constituents. Regarding its anti-Candida activity, the oil inhibited the growth of C. albicans (IC50 : 371 µg/mL) and C. tropicalis (IC50 : 830 µg/mL). Furthermore, the oil reversed the antifungal resistance of C. albicans and C. tropicalis, restoring the susceptibility to fluconazole and reducing their IC50 from 12.33 µg/mL and 362 µg/mL to 0.22 µg/mL and 13.93 µg/mL, respectively. The fixed oil of C. coriaceum completely inhibited the morphological transition of C. albicans and C. tropicalis at a concentration of 512 µg/mL, but exhibited limited low antifungal potential against C. krusei. The observed antifungal activity may be attributed to the overproduction of reactive oxygen species. Additionally, the oil showed no toxic effect on the Drosophila melanogaster in vivo model. The fixed oil from the inner mesocarp of C. coriaceum emerge as a strong candidate for the development of new pharmaceutical formulations to treat infections caused by Candida spp.

Assuntos

Fluconazol , Malpighiales , Animais , Fluconazol/farmacologia , Candida , Antifúngicos/farmacologia , Antifúngicos/química , Drosophila melanogaster , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Candida albicans , Testes de Sensibilidade Microbiana