RESUMO
This study assessed the physicochemical and antibiofilm properties of white mineral trioxide aggregate (MTA) associated with 1 or 2% of farnesol. Setting time was evaluated based on ISO 6876/2012. Radiopacity was evaluated by radiographic analysis. pH was assessed after time intervals of 1, 3, 7, 14, 21, and 28 days. Solubility (% mass loss) and volumetric change (by micro-CT) of the cements were evaluated after immersion in distilled water. The presence of voids inside the materials was assessed by using micro-CT. Antibiofilm activity against Enterococcus faecalis was evaluated by crystal violet assay and the modified direct contact test performed with biofilm previously formed on bovine root dentin for 14 days. Data were submitted to ANOVA/Tukey tests with 5% significance level. The incorporation of farnesol into MTA increased its setting time, but decreased its solubility at 30 days and its volumetric loss in all periods (p < 0.05). Radiopacity and solubility after 7 days were similar among the materials (p > 0.05). The association of farnesol showed the highest pH value after 1 and 3 days (p < 0.05). The association of farnesol with MTA promoted a decrease in the presence of voids, and increased the antimicrobial activity on biofilm biomass of E. faecalis (p < 0.05). In conclusion, the addition of farnesol can be suggested to improve the antimicrobial properties and the consistency of MTA.
Assuntos
Compostos de Alumínio , Biofilmes , Compostos de Cálcio , Combinação de Medicamentos , Enterococcus faecalis , Farneseno Álcool , Teste de Materiais , Óxidos , Materiais Restauradores do Canal Radicular , Silicatos , Solubilidade , Silicatos/farmacologia , Silicatos/química , Óxidos/farmacologia , Óxidos/química , Biofilmes/efeitos dos fármacos , Compostos de Cálcio/farmacologia , Compostos de Cálcio/química , Enterococcus faecalis/efeitos dos fármacos , Compostos de Alumínio/farmacologia , Compostos de Alumínio/química , Farneseno Álcool/farmacologia , Farneseno Álcool/química , Concentração de Íons de Hidrogênio , Fatores de Tempo , Bovinos , Materiais Restauradores do Canal Radicular/farmacologia , Materiais Restauradores do Canal Radicular/química , Animais , Análise de Variância , Reprodutibilidade dos Testes , Dentina/efeitos dos fármacos , Valores de Referência , Propriedades de Superfície/efeitos dos fármacosRESUMO
Farnesol is a natural essential oil with antimicrobial properties. Complexation of farnesol in chitosan nanoparticles can be useful to improve its bioavailability and potentiate its antifungal capabilities such as inhibition of hyphal and biofilm formation. The aim of this study was to develop and characterize chitosan nanoparticles with farnesol (NF) and evaluate their toxicity and antifungal action on C. albicans in vivo. The NF were prepared by the ionic gelation method and showed physicochemical characteristics such as diameter less than 200 nm, monodisperse distribution, positive zeta potential, spherical morphology, and stability after 120 days of storage. In the evaluation of toxicity in Galleria mellonella, NF did not reduce the survival rate, indicating that there was no toxicity in vivo at the doses tested. In the assays with G. mellonella infected by C. albicans, the larvae treated with NF had a high survival rate after 48 h, with a significant reduction of the fungal load and inhibition of the formation of biofilms and hyphae. In the murine model of vulvovaginal candidiasis (VVC), histopathological analysis showed a reduction in inflammatory parameters, fungal burden, and hyphal inhibition in mice treated with NF. The produced nanoparticles can be a promising alternative to inhibit C. albicans infection.
Assuntos
Quitosana , Nanopartículas , Animais , Camundongos , Candida albicans , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farneseno Álcool/farmacologia , Quitosana/farmacologia , Biofilmes , Nanopartículas/químicaRESUMO
Introduction: Farnesol, derived from farnesyl pyrophosphate in the sterols biosynthetic pathway, is a molecule with three unsaturations and four possible isomers. Candida albicans predominantly secretes the trans, trans-farnesol (t, t-FOH) isomer, known for its role in regulating the virulence of various fungi species and modulating morphological transition processes. Notably, the evolutionary divergence in sterol biosynthesis between fungi, including Candida albicans, and trypanosomatids resulted in the synthesis of sterols with the ergostane skeleton, distinct from cholesterol. This study aims to assess the impact of exogenously added trans, trans-farnesol on the proliferative ability of Leishmania amazonensis and to identify its presence in the lipid secretome of the parasite. Methods: The study involved the addition of exogenous trans, trans-farnesol to evaluate its interference with the proliferation of L. amazonensis promastigotes. Proliferation, cell cycle, DNA fragmentation, and mitochondrial functionality were assessed as indicators of the effects of trans, trans-farnesol. Additionally, lipid secretome analysis was conducted, focusing on the detection of trans, trans-farnesol and related products derived from the precursor, farnesyl pyrophosphate. In silico analysis was employed to identify the sequence for the farnesene synthase gene responsible for producing these isoprenoids in the Leishmania genome. Results: Exogenously added trans, trans-farnesol was found to interfere with the proliferation of L. amazonensis promastigotes, inhibiting the cell cycle without causing DNA fragmentation or loss of mitochondrial functionality. Despite the absence of trans, trans-farnesol in the culture supernatant, other products derived from farnesyl pyrophosphate, specifically α-farnesene and ß-farnesene, were detected starting on the fourth day of culture, continuing to increase until the tenth day. Furthermore, the identification of the farnesene synthase gene in the Leishmania genome through in silico analysis provided insights into the enzymatic basis of isoprenoid production. Discussion: The findings collectively offer the first insights into the mechanism of action of farnesol on L. amazonensis. While trans, trans-farnesol was not detected in the lipid secretome, the presence of α-farnesene and ß-farnesene suggests alternative pathways or modifications in the isoprenoid metabolism of the parasite. The inhibitory effects on proliferation and cell cycle without inducing DNA fragmentation or mitochondrial dysfunction raise questions about the specific targets and pathways affected by exogenous trans, trans-farnesol. The identification of the farnesene synthase gene provides a molecular basis for understanding the synthesis of related isoprenoids in Leishmania. Further exploration of these mechanisms may contribute to the development of novel therapeutic strategies against Leishmania infections.
Assuntos
Leishmania mexicana , Leishmania , Farneseno Álcool/metabolismo , Farneseno Álcool/farmacologia , Leishmania mexicana/metabolismo , Leishmania/metabolismo , Esteróis/análise , Esteróis/farmacologia , Candida albicansRESUMO
The efflux systems are considered important mechanisms of bacterial resistance due to their ability to extrude various antibiotics. Several naturally occurring compounds, such as sesquiterpenes, have demonstrated antibacterial activity and the ability to inhibit efflux pumps in resistant strains. Therefore, the objective of this research was to analyze the antibacterial and inhibitory activity of the efflux systems NorA, Tet(K), MsrA, and MepA by sesquiterpenes nerolidol, farnesol, and α-bisabolol, used either individually or in liposomal nanoformulation, against multi-resistant Staphylococcus aureus strains. The methodology consisted of in vitro testing of the ability of sesquiterpenes to reduce the Minimum Inhibitory Concentration (MIC) and enhance the action of antibiotics and ethidium bromide (EtBr) in broth microdilution assays. The following strains were used: S. aureus 1199B carrying the NorA efflux pump, resistant to norfloxacin; IS-58 strain carrying Tet(K), resistant to tetracyclines; RN4220 carrying MsrA, conferring resistance to erythromycin. For the EtBr fluorescence measurement test, K2068 carrying MepA was used. It was observed the individual sesquiterpenes exhibited better antibacterial activity as well as efflux pump inhibition. Farnesol showed the lowest MIC of 16.5 µg/mL against the S. aureus RN4220 strain. Isolated nerolidol stood out for reducing the MIC of EtBr to 5 µg/mL in the 1199B strain, yielding better results than the positive control CCCP, indicating strong evidence of NorA inhibition. The liposome formulations did not show promising results, except for liposome/farnesol, which reduced the MIC of EtBr against 1199B and RN4220. Further research is needed to evaluate the mechanisms of action involved in the inhibition of resistance mechanisms by the tested compounds.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Sesquiterpenos , Farneseno Álcool/farmacologia , Staphylococcus aureus/metabolismo , Staphylococcus aureus Resistente à Meticilina/metabolismo , Lipossomos , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Antibacterianos/farmacologia , Sesquiterpenos/farmacologia , Etídio/farmacologia , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/metabolismoRESUMO
Salirasib, or farnesylthiosalicylic acid (FTS), is a salicylic acid derivative with demonstrated antineoplastic activity. While designed as a competitor of the substrate S-farnesyl cysteine on Ras, it is a potent competitive inhibitor of isoprenylcysteine carboxymethyl transferase. In this study, the antiproliferative activity on six different solid tumor cell lines was evaluated with a series of lipophilic thioether modified salirasib analogues, including those with or without a 1,2,3-triazole linker. A combination of bioassay, cheminformatics, docking, and in silico ADME-Tox was also performed. SAR analysis that analogues with three or more isoprene units or a long aliphatic chain exhibited the most potent activity. Furthermore, three compounds display superior antiproliferative activity than salirasib and similar potency compared to control anticancer drugs across all tested solid tumor cell lines. In addition, the behavior of the collection on migration and invasion, a key process in tumor metastasis, was also studied. Three analogues with specific antimigratory activity were identified with differential structural features being interesting starting points on the development of new antimetastatic agents. The antiproliferative and antimigratory effects observed suggest that modifying the thiol aliphatic/prenyl substituents can modulate the activity.
Assuntos
Antineoplásicos , Antineoplásicos/farmacologia , Salicilatos/farmacologia , Farneseno Álcool/farmacologia , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Isoprenoids are the output of the polymerization of five-carbon, branched isoprenic chains derived from isopentenyl pyrophosphate (IPP) and its isomer, dimethylallyl pyrophosphate (DMAPP). Isoprene units are consecutively condensed to form longer structures such as farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively), necessary for the biosynthesis of several metabolites. Polyprenyl transferases and synthases use polyprenyl pyrophosphates as their natural substrates; however, it is known that free polyprenols, such as farnesol (FOH), and geranylgeraniol (GGOH) can be incorporated into prenylated proteins, ubiquinone, cholesterol, and dolichols. Furthermore, FOH and GGOH have been shown to block the effects of isoprenoid biosynthesis inhibitors such as fosmidomycin, bisphosphonates, or statins in several organisms. This phenomenon is the consequence of a short pathway, which was observed for the first time more than 25 years ago: the polyprenol salvage pathway, which works via the phosphorylation of FOH and GGOH. Biochemical studies in bacteria, animals, and plants suggest that this pathway can be carried out by two enzymes: a polyprenol kinase and a polyprenyl-phosphate kinase. However, to date, only a few genes have been unequivocally identified to encode these enzymes in photosynthetic organisms. Nevertheless, pieces of evidence for the importance of this pathway abound in studies related to infectious diseases, cancer, dyslipidemias, and nutrition, and to the mitigation of the secondary effects of several drugs. Furthermore, nowadays it is known that both FOH and GGOH can be incorporated via dietary sources that produce various biological effects. This review presents, in a simplified but comprehensive manner, the most important data on the FOH and GGOH salvage pathway, stressing its biomedical importance The main objective of this review is to bring to light the need to discover and characterize the kinases associated with the isoprenoid salvage pathway in animals and pathogens.
Assuntos
Diterpenos , Inibidores de Hidroximetilglutaril-CoA Redutases , Animais , Farneseno Álcool/farmacologia , Diterpenos/farmacologia , Diterpenos/metabolismo , Terpenos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologiaRESUMO
Biofilms are important to the virulence of human pathogenic fungi, and some molecules have been found to play key roles in the growth and regulation of fungal biofilms. Farnesol, one of these molecules, is well-described for some microorganisms but is still scarcely known for Rhodotorula spp. This study aimed to evaluate the influence of farnesol on the biofilm of R. mucilaginosa. Initially, screening with 0.2 mM to 2.1 mM of farnesol was evaluated against planktonic forms. A concentration of this compound was then chosen and evaluated for its effect on biofilm in formation and on preformed biofilm after 24, 48 and 72 hours. The impact of farnesol was evaluated by colony-forming units (CFU) counts, determination of metabolic activity and quantification of total biomass. In the presence of 0.9 mM, farnesol was able to decrease the CFU number, at 48 hours, when the biofilm was in formation, although it did not affect the preformed biofilms. Thus, our results show that farnesol exerts a modulating activity during biofilm formation for R. mucilaginosa, with this compound reducing the metabolic activity and total biomass of the biofilms.
Assuntos
Farneseno Álcool , Rhodotorula , Biofilmes , Farneseno Álcool/farmacologia , Humanos , Plâncton/fisiologiaRESUMO
Nonalcoholic fatty liver disease (NAFLD), often associated with obesity, is becoming one of the most common liver diseases worldwide. It is estimated to affect one billion individuals and may be present in approximately 25% of the population globally. NAFLD is viewed as a hepatic manifestation of metabolic syndrome, with humans and animal models presenting dyslipidemia, hypertension, and diabetes. The gut-liver axis has been considered the main pathogenesis branch for NAFLD development. Considering that foods or beverages could modulate the gastrointestinal tract, immune system, energy homeostasis regulation, and even the gut-liver axis, we conducted an exploratory study to analyze the effects of kombucha probiotic on hepatic steatosis, glucose tolerance, and hepatic enzymes involved in carbohydrate and fat metabolism using a pre-clinical model. The diet-induced obese mice presented glucose intolerance, hyperinsulinemia, hepatic steatosis, increased collagen fiber deposition in liver vascular spaces, and upregulated TNF-alpha and SREBP-1 gene expression. Mice receiving the kombucha supplement displayed improved glucose tolerance, reduced hyperinsulinemia, decreased citrate synthase and phosphofructokinase-1 enzyme activities, downregulated G-protein-coupled bile acid receptor, also known as TGR5, and farnesol X receptor gene expression, and attenuated steatosis and hepatic collagen fiber deposition. The improvement in glucose tolerance was accompanied by the recovery of acute insulin-induced liver AKT serine phosphorylation. Thus, it is possible to conclude that this probiotic drink has a beneficial effect in reducing the metabolic alterations associated with diet-induced obesity. This probiotic beverage deserves an extension of studies to confirm or refute its potentially beneficial effects.
Assuntos
Resistência à Insulina , Chá de Kombucha , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Citrato (si)-Sintase/metabolismo , Farneseno Álcool/metabolismo , Farneseno Álcool/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fígado , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Insulina/metabolismo , Glucose/metabolismo , Ácidos e Sais Biliares/metabolismo , Carboidratos/farmacologia , Serina/metabolismo , Serina/farmacologia , Fosfofrutoquinase-1/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Colágeno/metabolismo , Camundongos Endogâmicos C57BL , Dieta HiperlipídicaRESUMO
Enterococcus faecalis is related to the recurrence of endodontic infections and approaches to intracanal disinfection are necessary. Farnesol, an alcohol commonly found in propolis, has antimicrobial properties, and can enhance the efficacy of some antibiotic therapies. The objective was to evaluate whether farnesol can increase the efficacy of the antimicrobial photodynamic inactivation (aPDI) on E. faecalis, investigating its action on planktonic growth, biofilms, and cell permeability. Planktonic cells and biofilms of E. faecalis were pre-treated with farnesol (0.25 mM) 2 h before aPDI. Methylene blue (1 mg/mL) and laser (660 nm) were employed in the aPDI. As a result, farnesol was able to increase the antimicrobial activity of aPDI in both planktonic and biofilm stages, reaching cell reductions of 4.6 to 6 log10 CFU and 1.3 to 3 log10 CFU, respectively, when compared to aPDI isolated. The efficacy of farnesol in enhancing the anti-biofilm activity of aPDI was also confirmed by electron microscopy, in which a smaller number of bacterial cells and extracellular matrix were verified in the combined therapy compared to aPDI alone. The potentiating action of farnesol was associated with its effects in increasing the cell permeability and methylene blue uptake by the bacterial cells. Therefore, farnesol can be a promising potentiator of aPDI against E. faecalis.
Assuntos
Anti-Infecciosos , Fotoquimioterapia , Antibacterianos , Anti-Infecciosos/farmacologia , Biofilmes , Enterococcus faecalis , Farneseno Álcool/farmacologia , Azul de Metileno/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , PlânctonRESUMO
Biofilms are important virulence factor in infections caused by microorganisms because of its complex structure, which provide resistance to conventional antimicrobials. Strategies involving the use of molecules capable of inhibiting their formation and also act synergistically with conventional drugs have been explored. Farnesol is a molecule present in essential oils and produced by Candida albicans as a quorum sensing component. This sesquiterpene presents inhibitory properties in the formation of microbial biofilms and synergism with antimicrobials used in clinical practice, and can be exploited even for eradication of biofilms formed by drug-resistant microorganisms. Despite this, farnesol has physical and chemical characteristics that can limit its use, such as high hydrophobicity and volatility. Therefore, nanotechnology may represent an option to improve the efficiency of this molecule in high complex environments such as biofilms. Nanostructured systems present important results in the improvement of treatment with different commercial drugs and molecules with therapeutic or preventive potential. The formation of nanoparticles offers advantages such as protection of the incorporated drugs against degradation, improved biodistribution and residence time in specific treatment sites. The combination of farnesol with nanotechnology may be promising for the development of more effective antibiofilm therapies, as it can improve its solubility, reduce volatility, and increase bioavailability. This review summarizes existing data about farnesol, its action on biofilms, and discusses its encapsulation in nanostructured systems. LAY SUMMARY: Farnesol is a natural compound that inhibits the formation of biofilms from different microbial species. The encapsulation of this molecule in nanoparticles is a promising alternative for the development of more effective therapies against biofilms.
Assuntos
Biofilmes , Farneseno Álcool , Animais , Candida albicans , Farneseno Álcool/farmacologia , Nanotecnologia , Distribuição TecidualRESUMO
Farnesol (FAR) is a sesquiterpene alcohol with a range of reported biological effects including cardioprotective, antioxidant and antiarrhythmic properties. However, due to its volatility, the use of drug incorporation systems, such as cyclodextrins, have been proposed to improve its pharmacological properties. Thus, the aim of this study was to evaluate and characterize the cardiovascular effects of FAR alone, and to investigate the antihypertensive effects of FAR complexed with ß-cyclodextrin (ßCD) in rats. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after intravenous administration of FAR (0,5; 2,5; 5 and 7,5 mg/kg) in normotensive rats, and after oral acute administration (200 mg/kg) of FAR and FAR/ßCD complex in NG-nitro-L-arginine-methyl-ester (L-NAME) hypertensive rats. In normotensive animals, FAR induced dose-dependent hypotension associated with bradycardia. These effects were not affected by pre-treatment with L-NAME or indomethacin (INDO), but were partially attenuated by atropine. Pre-treatment with hexamethonium (HEXA) only affected hypotension. In the hypertensive rats, FAR/ßCD potentialized the antihypertensive effect when compared to FAR alone. Molecular docking experiments demonstrated for the first time that FAR has affinity to bind to the M3 and M2 muscarinic, and nicotinic receptors through hydrogen bonds in the same residues as known ligands. In conclusion, our results demonstrated that FAR induced hypotension associated with bradycardia, possibly through the muscarinic and nicotinic receptors. The inclusion complex with ßCD improved the antihypertensive effects of FAR, which can be relevant to improve current cardiovascular therapy using volatile natural components.
Assuntos
Fármacos Cardiovasculares/farmacologia , Farneseno Álcool/farmacologia , Hipertensão/tratamento farmacológico , beta-Ciclodextrinas/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/tratamento farmacológico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Simulação de Acoplamento Molecular , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos , Ratos WistarRESUMO
Chlamydoconidium-producing Trichophyton tonsurans strains isolated in Northeastern Brazil have morphological features different from the classic description of this dermatophyte species. This study investigated the phylogenetic relationship of chlamydoconidium-producing T. tonsurans strains isolated in Northeastern Brazil. Also, the effect of terbinafine and farnesol on mature biofilms of T. tonsurans strains was evaluated. The mass spectra of T. tonsurans strains were investigated by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The ITS and LSU loci regions of rDNA and the partial ß-tubulin gene were sequenced and the phylogenetic tree was analysed. The effects of terbinafine and farnesol on mature T. tonsurans biofilms were evaluated through the analysis of metabolic activity, quantification of biomass and observation by scanning electron microscopy. MALDI-TOF MS spectra of the chlamydoconidium-producing T. tonsurans strains differed from the spectrum of the control strain (ATCC 28942), presenting an intense ion peak at m/z 4155 Da. Phylogenetic tree analysis showed that the chlamydoconidium-producing strains isolated in Northeastern Brazil are allocated to a single cluster, differing from strains isolated from other countries. As for mature T. tonsurans biofilms, farnesol reduced biomass and metabolic activity by 64.4 and 65.9â%, respectively, while terbinafine reduced the biomass by 66.5â% and the metabolic activity by 69â%. Atypical morphological characteristics presented by chlamydoconidium-producing T. tonsurans strains result from phenotypic plasticity, possibly for adaptation to environmental stressors. Also, farnesol had inhibitory activity against T. tonsurans biofilms, demonstrating this substance can be explored for development of promising anti-biofilm drugs against dermatophytes.
Assuntos
Antifúngicos/farmacologia , Arthrodermataceae/classificação , Biofilmes/efeitos dos fármacos , Filogenia , Arthrodermataceae/citologia , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/fisiologia , Biofilmes/crescimento & desenvolvimento , Brasil , DNA Fúngico/genética , DNA Ribossômico/genética , Farneseno Álcool/farmacologia , Proteínas Fúngicas/genética , Humanos , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Esporos Fúngicos/classificação , Esporos Fúngicos/citologia , Terbinafina/farmacologia , Tubulina (Proteína)/genéticaRESUMO
Candida infections represent a threat to human health. Candida albicans is the main causative agent of invasive candidiasis, especially in immunosuppressed patients. The emergence of resistant strains has required the development of new therapeutic strategies. In this context, the use of liposomes as drug carrier systems is a promising alternative in drug development. Thus, considering the evidence demonstrating that sesquiterpene farnesol is a bioactive compound with antifungal properties, this study evaluated the activity farnesol-containing liposomes against different Candida strains. The IC50 of farnesol and its liposomal formulation was assessed in vitro using cultures of Candida albicans, Candida tropicalis, and Candida krusei. The Minimum Fungicidal Concentration (MFC) was established by subculture in solid medium. The occurrence of fungal dimorphism was analyzed using optical microscopy. The effects on antifungal resistance to fluconazole were assessed by evaluating the impact of combined therapy on the growth of Candida strains. The characterization of liposomes was carried out considering their vesicular size, polydispersion index, and zeta medium potential, in addition to electron microscopy analysis. Farnesol exerted an antifungal activity that might be associated with the inhibition of fungal dimorphism, especially in Candida albicans. The incorporation of farnesol into liposomes significantly increased its antifungal activity against C. albicans, C. tropicalis, and C. krusei. In addition, liposomal farnesol potentiated the action of fluconazole against C. albicans and C. tropicalis. On the other hand, the association of unconjugated farnesol with fluconazole resulted in antagonistic effects. In conclusion, farnesol-containing liposomes have the potential to be used in antifungal drug development. However, further research is required to investigate how the antifungal properties of farnesol are affected by the interaction with liposomes, contributing to the modulation of antifungal resistance to conventional drugs.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Farneseno Álcool/farmacologia , Fluconazol/farmacologia , Antifúngicos/química , Farmacorresistência Fúngica/efeitos dos fármacos , Farneseno Álcool/química , Fluconazol/química , Lipossomos/química , Lipossomos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
This study investigated the effect of the quorum sensing molecules (QSMs) farnesol, 2-phenylehtanol, tyrosol and tryptophol against planktonic cells, filamentation and biofilms of Sporothrix spp. The antifungal activity of QSMs was evaluated by broth microdilution. QSMs showed MICs in the ranges of 0.01-1 µM (farnesol), 1-8 mM (2-phenylehtanol and tyrosol), and >16 mM (tryptophol). Filamentous biofilm formation was inhibited by farnesol and 2-phenylehtanol and stimulated by tyrosol. Yeast biofilm formation was inhibited by 2-phenylehtanol and tyrosol. Tryptophol did not affect Sporothrix biofilm formation. QSMs showed MICs against mature biofilms of 8-32 µM (farnesol), 8-32 mM (2-phenylehtanol) and 64-128 mM (tyrosol). In conclusion, farnesol, 2-phenylethanol and tyrosol have antifungal activity against planktonic and sessile cells and modulate filamentation and biofilm formation in Sporothrix spp.
Assuntos
Percepção de Quorum , Sporothrix , Antifúngicos/farmacologia , Biofilmes , Farneseno Álcool/farmacologia , PlânctonRESUMO
Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (C15H26O), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE2, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.
Assuntos
Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Farneseno Álcool/farmacologia , Farneseno Álcool/uso terapêutico , Animais , Óleo de Rícino , Cloretos/metabolismo , Toxina da Cólera , Diarreia/induzido quimicamente , Dinoprostona , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Secreções Intestinais/metabolismo , Masculino , Camundongos , Simulação de Acoplamento Molecular , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Receptores de Superfície Celular/metabolismoRESUMO
Introduction: Farnesol (C15H26O) is a sesquiterpene alcohol found in essential oils. This substance is reported to have different pharmacological activities such as antimicrobial, antitumor and antioxidant effects, as well as actions in different body systems.Areas covered: This study aimed to analyze pharmaceutical patents containing this substance in their formulations. Patent search was carried out through the WIPO (World Intellectual Property Organization), LatiPat and INPI (National Institute of Industrial Property) electronic banks using the following descriptors and combinations: 'farnesol', 'pharmaceutical product', 'pharmacology' and 'pharmacy'.Expert opinion: Primary research identified 54 patents, from which 17 were selected for the final analysis after applying the inclusion criteria. The selected patents referred to products presenting different pharmaceutical activities of interest such as the prevention and treatment of diseases affecting the dermis, central nervous and cardiovascular systems, diseases caused by different microorganisms and cancers, among others. A minority of the articles included in this review reported the type of farnesol isomer that was investigated, this becoming a major limitation for the development of future pharmaceutical products. With the completion of this study, farnesol presents itself as a potential agent with pharmacological application both in the prevention and treatment of different diseases.
Assuntos
Farneseno Álcool/administração & dosagem , Óleos Voláteis/química , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Farneseno Álcool/farmacologia , Humanos , Patentes como AssuntoRESUMO
A biofilm is represented by a community of microorganisms capable of adhering to a surface and producing substances that envelop the cells, forming an extracellular matrix. The extracellular matrix is responsible for protecting microorganisms against environmental stress, hosts the immune system and confers resistance to antimicrobials. Fusarium keratoplasticum is a common species of FSSC (Fusarium solani species complex) associated with human infections, being the most prevalent species related to biofilm formation in hospital water systems and internal pipelines. With this in mind, this study aimed to characterise the biofilm formed by the fungus F. keratoplasticum and to evaluate the effects of farnesol, a fungal quorum sensing (QS) molecule, on the preformed biofilm and also during its formation at different times (adhesion and 24, 48 and 72 h). F. keratoplasticum is able to adhere to an abiotic surface and form a dense biofilm in 72 h, with increased total biomass and matrix modulation with the presence of extracellular DNA, RNA, polysaccharides and proteins. Farnesol exhibited important anti-biofilm activity, causing the destruction of hyphae and the extracellular matrix in preformed biofilm and preventing the adhesion of conidia, filamentation and the formation of biofilm. Few studies have characterised the formation of biofilm by filamentous fungi. Our findings suggest that farnesol acts efficiently on F. keratoplasticum biofilm since this molecule is capable of breaking the extracellular matrix, thereby disarranging the biofilm.
Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Farneseno Álcool/farmacologia , Fusarium/efeitos dos fármacos , Animais , Chlorocebus aethiops , Células HeLa , Humanos , Hifas/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Esporos Fúngicos/efeitos dos fármacos , Células VeroRESUMO
A series of experiments were conducted to characterize a novel restorative material. We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM). Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control). Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM. 3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology. Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength. Chemical assay: Raman spectroscopy. The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05). Polysaccharides levels increased over time, similarly over groups (p>0.05). Viable and non-viable S. mutans were seen on the specimens' surface by CLSM but their virulence was not modulated by tt-farnesol. The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05). Raman confirmed the presence of tt-farnesol. The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices. Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Farneseno Álcool/análogos & derivados , Farneseno Álcool/farmacologia , Cimentos de Ionômeros de Vidro/química , Cimentos de Ionômeros de Vidro/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Dureza , Humanos , Teste de Materiais , Viabilidade Microbiana/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/fisiologia , Resistência à TraçãoRESUMO
OBJECTIVE: This study aimed to evaluate the antimicrobial and biofilm anti-adhesion activities of poly(vinyl alcohol)-coated silver nanoparticles (AgNPs-PVA) and farnesol against Enterococcus faecalis, Candida albicans or Pseudomonas aeruginosa. DESIGN: Minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) of the solutions, as well as the effect on the biofilm biomass were evaluated. The biofilm anti-adhesion activity was evaluated using bovine root dentine treated with the solutions after 3â¯min of contact and analyzed by scanning electron microscopy (SEM) and by colony-forming units per milliliter (CFUâ¯mL-1) counting. Data were analyzed using ANOVA and Tukey's, the paired Student's t-test or Kruskal-Wallis and Dunn's tests (αâ¯=â¯0.05). RESULTS: The MIC and MMC values (MIC/MMC) of the AgNPs-PVA and farnesol against E. faecalis were 42.5/50⯵M and 0.85/1.0%, respectively. For C. albicans, the values were 27.5/37.5⯵M and 1.75/2.5%; and for P. aeruginosa, 32.5/32.5⯵M and 2.5/2.75%, respectively. Both solutions showed reduced biofilm biomass (pâ¯<â¯0.05). SEM analysis showed that dentine blocks treated with both solutions had lower biofilm formation than the control (saline), except for C. albicans. In the CFUâ¯mL-1 counting, biofilm cells were viable in the all groups in comparison with control (pâ¯>â¯0.05). CONCLUSIONS: AgNPs-PVA and farnesol showed antimicrobial and biofilm anti-adhesion activities, as well as potential for use as coadjuvant in endodontic treatment, and may be an option as auxiliary procedure for root canal disinfection or to inhibit biofilm formation.
Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Farneseno Álcool/farmacologia , Nanopartículas Metálicas , Irrigantes do Canal Radicular/farmacologia , Prata/farmacologia , Animais , Aderência Bacteriana/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Bovinos , Cavidade Pulpar , Enterococcus faecalis/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
Cardiac arrhythmias are among the most important pathologies that lead to sudden death. The discovery of new therapeutic options against arrhythmias with low adverse effects is of paramount importance. Farnesol is found in essential oils with antioxidant, anti-inflammatory and cardioprotective properties. The aim of this work was to investigate the effects of farnesol on the contractile and electrophysiological properties in rat heart and evaluate its antiarrhythmic action. It was evaluated farnesol effects on the left ventricular developed pressure, ECG, potassium (Ik) and L-type Ca2+ currents (ICa,L), action potential, intracellular Ca2+ transient, Ca2+ sparks and waves and reactive oxygen species production. Antiarrhythmic activity of farnesol was determined in vivo and ex vivo. The results showed that 50⯵M farnesol did not alter left ventricular developed pressure, heart rate, ECG parameters and intracellular Ca2+ transient but reduced ICa,L. Farnesol reduced action potential duration at 90% repolarization. Notably, farnesol improved arrhythmia score and the incidence of the most severe arrhythmias. Farnesol attenuated the generation of reactive oxygen species, Ca2+ sparks and waves in isolated cardiomyocytes submitted to Ca2+ overload. In conclusion, farnesol has antiarrhythmic effect mediated by reducing of ICa,L and IK along with a decrease of reactive oxygen species production and normalized Ca2+ sparks and waves.