RESUMO
This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
Assuntos
Emulsões , Macrófagos Peritoneais , Sesquiterpenos Monocíclicos , Sesquiterpenos , Pele , Animais , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Monocíclicos/química , Emulsões/química , Camundongos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Pele/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Espectroscopia de Infravermelho com Transformada de Fourier , Absorção Cutânea/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Feminino , Leishmania/efeitos dos fármacos , Tensoativos/farmacologia , Tensoativos/química , Antiprotozoários/farmacologia , Antiprotozoários/químicaRESUMO
α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 µg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.
Assuntos
Emulsões , Sesquiterpenos Monocíclicos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ratos , Emulsões/química , Reprodutibilidade dos Testes , Sesquiterpenos Monocíclicos/farmacocinética , Sesquiterpenos Monocíclicos/sangue , Sesquiterpenos Monocíclicos/química , Masculino , Projetos Piloto , Modelos Lineares , Limite de Detecção , Sesquiterpenos/farmacocinética , Sesquiterpenos/sangue , Sesquiterpenos/química , Ratos Sprague-Dawley , Espectrofotometria Ultravioleta/métodosRESUMO
The natural antimicrobial properties of essential oils (EOs) have contributed to the battle against multidrug-resistant microorganisms by providing new ways to develop more effective antibiotic agents. In this study, we investigated the chemical composition of Ocotea diospyrifolia essential oil (OdOE) and its antimicrobial properties combined with amikacin (AMK). Through gas chromatography-mass spectrometry (GCMS) analysis, the primary constituents of OdOE were identified as α-bisabolol (45.8 %), ß-bisabolene (9.4 %), γ-elemene (7.6 %), (Z)- ß-farnesene (5.2 %), spathulenol (3.5 %), (Z)-caryophyllene (3.3 %), and (E)-caryophyllene (3.1 %). In vitro assessments showed that the combined administration of OdOE and AMK exerted a synergistic antibacterial effect on the multidrug-resistant K. pneumoniae strain. This synergistic effect demonstrated bacteriostatic action. OdEO combined with amikacin showed protein extravasation within 2 h of treatment, leading to bacterial death, which was determined by a reduction in viable cell count. The effective concentrations showed hemocompatibility. In vivo assessments using Caenorhabditis elegans as a model showed the survival of 85 % of infected nematodes. Therefore, the combination OdEO combined with amikacin exhibited antimicrobial activity against a multidrug-resistant K. pneumoniae strain. Thus, OdOE is a promising agent that may be considered for development of antimicrobial treatment.
Assuntos
Amicacina , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Óleos Voláteis , Amicacina/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Animais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Caenorhabditis elegans/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Sesquiterpenos/farmacologiaRESUMO
The indiscriminate use of synthetic herbicides reduces its effectiveness. Bioherbicides produced with metabolites emerge as an alternative to managing weeds. We aimed to analyze the phytotoxic potential of the essential oil of Vanillosmopsis arborea (EOVA) and the α-bisabolol molecule, its main component. We evaluated the effects of EOVA and α-bisabolol at different concentrations on the germination, growth, antioxidant metabolism, and photosynthesis of different species. EOVA and α-bisabolol showed promising phytotoxic effects on the germination and initial growth of the weed Senna occidentalis, inhibiting the activity of the antioxidant enzymes and increasing lipid peroxidation. α-Bisabolol reduced the weed seedling growth by inducing oxidative stress, which suggests a greater role in postemergence. Moreover, in the weed postemergence, both EOVA and α-bisabolol caused damage in the shoots, reduced the chlorophyll content, and increased lipid peroxidation besides reducing photosynthesis in S. occidentalis. Overall, we suggest the promising action of α-bisabolol and EOVA as bioherbicides for weed control.
Assuntos
Herbicidas , Controle de Plantas Daninhas , Antioxidantes , Sesquiterpenos Monocíclicos , Herbicidas/farmacologiaRESUMO
The essential oils prepared by hydrodistillation of twenty-one brands of German chamomile (S1-S21) commercialized in Mexico were analyzed by GS-MS. Altogether, twenty-four different compounds were identified in the analyzed samples, varying from 77 to 100 % of the total composition. Multivariate analyses were applied to explore similarity/dissimilarity and correlation between all samples; the results revealed a strong correlation among samples S4, S5, and S7-S21 due to the presence of (Z)-en-yn-dicycloether [(Z)-tonghaosu], α-bisabolol, ß-farnesene, ß-eudesmol, and xanthoxylin. The samples S1-S3 and S6 were clustered separately. Samples S1, S3, and S6 were characterized by their higher content of bisabolol oxide A (38.78 %, 51.84 %, and 70.46 %, respectively) as most known chemotypes of German chamomile, but only S1 and S3 contained chamazulene. Finally, S2 differed from the others because of its high content of (E)-anethole (62.28 %), suggesting a case of adulteration or substitution of the crude drug employed for manufacturing the product.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Matricaria , Óleos Voláteis , Óleos Voláteis/química , México , Matricaria/química , Sesquiterpenos/química , Sesquiterpenos/análise , Sesquiterpenos Monocíclicos/química , Derivados de Alilbenzenos/químicaRESUMO
Bauhinia ungulata is an antioxidant medicinal plant that has been manipuled in Brazil to lower glycemic index as well is for alternative treatment for diabetes. Therefore, the present hearch has aimed to investigates the antioxidant effects of the essential oil of Bauhinia ungulata L. (EOBU) collected in Amazon region better specified in Boa Vista, Roraima, Brazil, located in the Amazon region. Gas chromatography had been used to characterize the components, and antioxidant assays such as DPPH, TAC, reducing power, Fe2+ chelation, and total phenols had also been performed. The major constituents had molecularly anchored with the human catalase (CAT) enzyme, and maltol has showed as a positive control. Among the 25 revealed components, the main ones have been α-bisabolol (27.2 %), ß-Caryophyllene (12.5 %) and Epi-γ-eudesmol (13.6 %). The EOBU has comproved a TAC value of 618.79â mg of ascorbic acid equivalent, free radical scavenging capacity (DPPH) around 53.7 % and 65.27 %, Fe2+ chelation capacity of 161±6 and 126.7±39.6, for 0.1â mg.mL-1 and 0.5â mg.mL-1 , respectively. The power around the EOBU has appeared percentages equals to 28.66 %, 44.6 %, and 77.03 % in the concentrations tested. As well as, 96.5 % of total phenols. The compounds α-bisabolol (-5.7±0.4â Kcal.mol-1 ) and ß-caryophyllene (-6.1±0.5â Kcal.mol-1 ) have showed good interaction with CAT compared to Maltol (-4.4±0.4â Kcal.mol-1 ). The present work has demonstrated that EOBU functions as a potent antioxidant, capable of scavenging free radicals and reducing oxidative stress damage.
Assuntos
Bauhinia , Sesquiterpenos Monocíclicos , Óleos Voláteis , Sesquiterpenos Policíclicos , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Fenóis/química , Extratos Vegetais/químicaRESUMO
The objective of this study was to formulate an experimental light-cured periodontal dressing containing alpha-humulene and to compare its physical, antimicrobial, and cytotoxicity properties with commercial gold standards (Barricaid® and Periobond®). Two periodontal dressing formulations were developed (a and b). The formulations were divided into 5 groups according to the alpha-humulene concentration as follows: Ea - control group, Ea1 - 1%, Ea5 - 5%, Ea10 - 10%, and Ea20 - 20%; Eb - control group, Eb1 - 1%, Eb5 - 5%, Eb10 - 10%, and Eb20 - 20%. Materials characterization was performed using the degree of conversion, cohesive strength, sorption, and solubility assays. Antimicrobial assay was performed using the modified direct contact test against E. faecalis and S. aureus. Cytotoxicity was assessed by the cell viability experiment using L929 fibroblasts. In general, the cohesive strength values of materials decreased as the alpha-humulene concentration increased. All the experimental dressings showed antimicrobial activity against both bacteria tested. Cell viability results for the Ea, Ea1, Eb, and Eb1 groups showed moderate cytotoxic effect. The formulations containing alpha-humulene showed similar behavior to the commercial references. Thus, formulations containing alpha-humulene have potential to be used as periodontal dressing.
Assuntos
Anti-Infecciosos , Curativos Periodontais , Anti-Infecciosos/farmacologia , Sesquiterpenos Monocíclicos , Staphylococcus aureusRESUMO
INTRODUCTION: Amphotericin B (AmB), used for systemic fungal infections, has a limited clinical application because of its high nephrotoxicity. Natural antioxidant and anti-inflammatory substances have been widely studied for protection against drug-induced nephrotoxicity. α-Bisabolol (BIS) has demonstrated a nephroprotective effect on both in vitro and in vivo models. AIMS: The aim of this work was to evaluate the effect of BIS against AmB-induced nephrotoxicity in vitro. MATERIAL AND METHODS: LLC-MK2 cells were pre- and post-treated with non-toxic BIS concentrations and/or AmB IC50 (13.97 µM). Cell viability was assessed by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Flow cytometry analyses were used to assess cell death mechanism, production of reactive oxidative stress (ROS) and mitochondrial transmembrane potential. Kidney Injury Molecule-1 (KIM-1) levels were measured via ELISA. KEY FINDINGS: The present work showed that BIS pretreatment (125; 62.5 and 31.25 µM) increased cell viability when compared to the group treated only with AmB IC50. AmB treatment induced both necrosis (7-AAD-labeled cells) and late apoptosis (AnxV-labeled). BIS was able to prevent the occurrence of these events. These effects were associated with a decrease of ROS accumulation, improving transmembrane mitochondrial potential and protecting against tubular cell damage, highlighted by the inhibition of KIM-1 release after BIS treatment. SIGNIFICANCE: BIS presented a potential effect on model of renal cytotoxicity induced by AmB, bringing perspectives for the research of new nephroprotective agents.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Sesquiterpenos Monocíclicos/farmacologia , Anfotericina B/farmacologia , Anfotericina B/toxicidade , Animais , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Rim/metabolismo , Túbulos Renais Proximais/metabolismo , Macaca mulatta , Sesquiterpenos Monocíclicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologiaRESUMO
Varronia curassavica has anti-inflammatory properties because of the terpenes, α-humulene and ß-caryophyllene, present in the essential oil. The objective of this study was to evaluate the influence of seasonality on the essential oil of V. curassavica accessions. Leaves from six accessions were collected from the Germplasm Bank of the Federal University of Minas Gerais over 12 months. Correlations between the essential oil content and meteorological factors were determined. Gas chromatography analysis coupled with mass spectrometry was conducted to determine the chemical composition of the essential oil. The content and chemical composition of the oil varied throughout the year. Relative humidity was correlated with accessions ICA-VC2 (-0.64) and ICA-VC4 (0.68). ß-bourbonene, ß-elemene, spathulenol, germacrene, caryophyllene oxide, α-humulene, and ß-caryophyllene occurred in all accessions. Accession ICA-VC3 exhibited lower variation (22.17%), higher average (0.97%) essential oil, and maintained an average abundance of α-humulene greater than 2.6%, which is the amount necessary for phytotherapeutics.
Varronia curassavica tiene propiedades antiinflamatorias debido a los terpenos, α-humuleno y ß-cariofileno, presentes en el aceite esencial. El objetivo de este estudio fue evaluar la influencia de la estacionalidad en el aceite esencial de las accesiones de V. curassavica. Se recolectaron hojas de seis accesiones del Banco de Germoplasma de la Universidad Federal de Minas Gerais durante 12 meses. Se determinaron las correlaciones entre el contenido de aceite esencial y los factores meteorológicos. Se realizó un análisis de cromatografía de gases junto con espectrometría de masas para determinar la composición química del aceite esencial. El contenido y la composición química del aceite varió a lo largo del año. La humedad relativa se correlacionó con las accesiones ICA-VC2 (-0,64) e ICA-VC4 (0,68). En todas las accesiones aparecieron ß-bourboneno, ß-elemeno, espatulenol, germacreno, óxido de cariofileno, α-humuleno y ß-cariofileno. La accesión ICA-VC3 mostró una menor variación (22,17%), un promedio más alto (0,97%) de aceite esencial y mantuvo una abundancia media de α-humuleno superior al 2,6%, que es la cantidad necesaria para los fitoterápicos.
Assuntos
Estações do Ano , Sesquiterpenos/análise , Óleos Voláteis/química , Boraginaceae/química , Plantas Medicinais , Temperatura , Banco de Sementes , Sesquiterpenos Monocíclicos/análise , Sesquiterpenos Policíclicos/análise , UmidadeRESUMO
Croton ferrugineus Kunth is an endemic species of Ecuador used in traditional medicine both for wound healing and as an antiseptic. In this study, fresh Croton ferrugineus leaves were collected and subjected to hydrodistillation for extraction of the essential oil. The chemical composition of the essential oil was determined by gas chromatography equipped with a flame ionization detector and gas chromatography coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against three Gram-positive bacteria, one Gram-negative bacterium and one dermatophyte fungus. The radical scavenging properties of the essential oil was evaluated by means of DPPH and ABTS assays. The chemical analysis allowed us to identify thirty-five compounds representing more than 99.95% of the total composition. Aliphatic sesquiterpene hydrocarbon trans-caryophyllene was the main constituent with 20.47 ± 1.25%. Other main compounds were myrcene (11.47 ± 1.56%), ß-phellandrene (10.55 ± 0.02%), germacrene D (7.60 ± 0.60%), and α-humulene (5.49 ± 0.38%). The essential oil from Croton ferrugineus presented moderate activity against Candida albicans (ATCC 10231) with an MIC of 1000 µg/mL, a scavenging capacity SC50 of 901 ± 20 µg/mL with the ABTS method, and very strong antiglucosidase activity with an IC50 of 146 ± 20 µg/mL.
Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Croton/química , Inibidores Enzimáticos/química , Óleos Voláteis/química , Folhas de Planta/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/isolamento & purificação , Alcenos/química , Alcenos/isolamento & purificação , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/isolamento & purificação , Picratos/antagonistas & inibidores , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Ácidos Sulfônicos/antagonistas & inibidores , alfa-Glucosidases/químicaRESUMO
(-)-α-Bisabolol is a functional ingredient in various health and cosmetic products and has antibacterial, anti-inflammatory, and wound healing properties. (-)-α-Bisabolol is chemically synthesized and produced by steam distillation of essential oils extracted from Brazilian Candeia (Eremanthus erythropappus). To sustainably produce pure (-)-α-bisabolol, we previously engineered Escherichia coli to produce 9.1 g/L (-)-α-bisabolol via heterologous mevalonate pathways and (-)-α-bisabolol synthase (BOS) from German chamomile, Matricaria recutita (MrBOS). BOS has only been reported in MrBOS and Brazilian Candeia (EeBOS). The limited availability of BOS has made it difficult to achieve high titer and yield and large-scale (-)-α-bisabolol production. We identified a novel BOS in globe artichoke (CcBOS) and examined its functionality in vitro and in vivo. CcBOS showed higher catalytic efficiency and (-)-α-bisabolol production rates than those from MrBOS or EeBOS. In fed-batch fermentation, CcBOS generated the highest reported (-)-α-bisabolol titer to date (23.4 g/L). These results may facilitate economically viable industrial (-)-α-bisabolol production.
Assuntos
Cynara scolymus , Cynara , Scolymus , Sesquiterpenos , Brasil , Cynara scolymus/genética , Escherichia coli/genética , Sesquiterpenos MonocíclicosRESUMO
The aim of this study was to examine if the peripheral antinociception of α-bisabolol involves the participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous injection into the dorsal surface of the paw of vehicles or increasing doses of α-bisabolol (100-300 µg/paw). To determine whether the peripheral antinociception induced by α-bisabolol was mediated by either the opioid receptors or the NO-cGMP-K+ channels pathway, the effect of pretreatment (10 min before formalin injection) with the appropriate vehicles, naloxone, naltrexone, NG-nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]-oxadiazolo[4,2-a]quinoxalin-1-one (ODQ), glibenclamide, glipizide, apamin, charybdotoxin, tetraethylammonium, or 4-aminopyridine on the antinociceptive effects induced by local peripheral α-bisabolol (300 µg/paw) were assessed. α-Bisabolol produced antinociception during both phases of the formalin test. α-Bisabolol antinociception was blocked by L-NAME, ODQ, and all the K+ channels blockers. The peripheral antinociceptive effect produced by α-bisabolol was not blocked by the opioid receptor inhibitors. α-Bisabolol was able to active the NO-cGMP-K+ channels pathway to produce its antinoceptive effect. The participation of opioid receptors in the peripheral local antinociception induced by α-bisabolol is excluded.
Assuntos
Analgésicos/farmacologia , GMP Cíclico/metabolismo , Sesquiterpenos Monocíclicos/farmacologia , Óxido Nítrico/metabolismo , Nociceptividade/efeitos dos fármacos , Canais de Potássio/metabolismo , Receptores Opioides/metabolismo , Animais , Masculino , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/química , Canais de Potássio/genética , Ratos , Ratos Wistar , Receptores Opioides/química , Receptores Opioides/genéticaRESUMO
Fusarium infections result in reduced maize grain (Zea mays L.) yields and notable impacts on human and animal health. Research involving natural products to control fungi in food is a promising alternative. Combinations of α-bisabolol (AB) and sodium chloride (NaCl) may suggest the use of lower effective concentrations of the drugs. This study aimed to evaluate the antifungal potential of AB associated with NaCl against Fusarium oxysporum strains isolated from maize. Minimum inhibitory concentrations (MICs) values of AB and NaCl were determined by microdilution, and an association study was performed (checkerboard). Effects on fungal mycelial growth (poisoned substrate technique) and a maize grain contamination model were analyzed. AB presented MIC values ranging from 128 and 1024 µg/mL; NaCl inhibited fungal growth at 16,384 µg/mL. The AB/NaCl association study revealed synergism by decreasing inhibitory concentrations by eight times. In corn kernels, AB and NaCl, whether isolated (at MIC) or in association (at sub-inhibitory concentrations), significantly inhibited in vitro mycelial growth (P < 0.05). Further analysis of liquid from a canned maize sample also revealed the fungistatic effects of the compounds associations (P < 0.05). The results confirm the antifungal potential of AB, whether isolated or in association with NaCl to control F. oxysporum in maize.
Assuntos
Fusarium , Antifúngicos/farmacologia , Humanos , Sesquiterpenos Monocíclicos , Cloreto de Sódio , Zea maysRESUMO
This study aimed to investigate the acaricidal activity of (E)-cinnamaldehyde and α-bisabolol on populations of Rhipicephalus microplus with different resistance profiles. The adult immersion test (AIT) was used to characterize the susceptibility of tick populations (50 field populations) to synthetic acaricides: deltamethrin, amitraz, and chlorfenvinphos. The larval packet test (LPT) was used to determine the LC50 values for (E)-cinnamaldehyde (populations 1-25) and α-bisabolol (populations 26-50) at the concentrations of 0.31, 0.62, 1.25, 2.0, 2.5, 5.0 and 10.0â¯mg/mL. The susceptible strain Porto Alegre (POA) was used as a reference for calculating the resistance ratio (RR). In the AIT, deltamethrin did not show efficacy >95 % for any of the populations, whereas amitraz and chlorfenvinphos have presented efficacy >95 % for three (6 %) and 15 (30 %) populations, respectively. In the LPT, the LC50 values of (E)-cinnamaldehyde and α-bisabolol varied from 0.23 to 2.36â¯mg/mL and 1.57-3.01â¯mg/mL, respectively. The RR50 for (E)-cinnamaldehyde showed 20 (80 %) populations with values <1.0 and no population with values>1.5. As for α-bisabolol, only two (8%) populations have presented RR50 <1.0, whereas three (12 %) populations showed incipient resistance to this sesquiterpene (RR50 between 1.5 and 2.0). The results indicate that all studied tick populations showed low susceptibility to at least one of the commercial acaricides tested. In addition, comparison between the LC50 values of (E)-cinnamaldehyde and α-bisabolol for the field populations and the susceptible strain POA suggests that there is no cross-resistance of (E)-cinnamaldehyde and α-bisabolol for the tick populations evaluated, and that the differences in the LC50 values are due to population variations.
Assuntos
Acaricidas/farmacologia , Acroleína/análogos & derivados , Resistência a Medicamentos , Sesquiterpenos Monocíclicos/farmacologia , Rhipicephalus/efeitos dos fármacos , Acroleína/farmacologia , Animais , Brasil , FemininoRESUMO
Compounds having insecticidal activity can be used to control Aedes aegypti mosquitoes, a major worldwide vector, and several plants have a source of such molecules. A principal component analysis (PCA) was carried out to determine the criterion to select larvicidal metabolites. The insecticidal activity of seven selected metabolites by PCA was validated by determining its lethal concentrations 50 (LC50) by probit analysis. Six of the seven evaluated molecules presented LC50 values <100â¯ppm. The effects of these six molecules on acetylcholinesterase and the respiratory chain complexes of the mitochondria of Ae. aegypti were evaluated. Four metabolites presenting the highest inhibition effects on these targets were mixed in 11 different combinations, and the percentage of mortality of each mixture on Ae. aegypti larvae were determined. Secondary metabolites such as geranyl acetate, α-humulene, ß-caryophyllene, geraniol, nerol, and n-octanol presented LC50 values under 100â¯ppm (44, 41, 48, 84, 87, and 98â¯ppm, respectively), whereas 1,8-cineole presented a LC50 value of 183â¯ppm. We found that, geranyl acetate, α-humulene, ß-caryophyllene, nerol, n-octanol, and geraniol inhibited at least one of the six targets with an efficiency between 25 and 41%. Overall, the evaluation of the different mixtures revealed a synergistic effect between geranyl acetate and geraniol, and an antagonistic effect between α-humulene and ß-caryophyllene compounds.
Assuntos
Aedes/metabolismo , Inseticidas/toxicidade , Mitocôndrias/metabolismo , Controle de Mosquitos/métodos , Metabolismo Secundário , Acetatos/toxicidade , Monoterpenos Acíclicos/toxicidade , Animais , Sesquiterpenos Monocíclicos/toxicidade , Oxirredução , Sesquiterpenos Policíclicos/toxicidadeRESUMO
Nectandra megapotamica is a tree species that naturally occurs in the Atlantic Forest, Brazil. This paper aims to investigate the chemical composition and in vitro antibacterial, antileishmanial and antiproliferative activities of essential oil from N. megapotamica leaves (NM-EO). It displayed high antibacterial activity against Streptococcus mutans, S. sobrinus, Prevotella nigrescens and Bacteroides fragilis. NM-EO also exhibited high antileishmanial activity against promastigote forms of Leishmania amazonensis. Its antiproliferative activity was evaluated against the following cells: GM07429A (normal cell), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma) and M059J (human glioblastoma). Its major components, which were determined by GC-FID and GC-MS, were α-bisabolol (13.7%), bicyclogermacrene (10.9%), (E,E)-farnesene (10.6%), Z-caryophyllene (9.5%) and (E)-ß-farnesene (7.0%). These results suggest that N. megapotamica, a Brazilian plant, shows initial evidence of a new and alternative source of substances of medicinal interest.
Assuntos
Antibacterianos/farmacologia , Antiprotozoários/farmacologia , Lauraceae/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Antibacterianos/análise , Antibacterianos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antiprotozoários/química , Brasil , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Leishmania/efeitos dos fármacos , Sesquiterpenos Monocíclicos/análise , Folhas de Planta/química , Sesquiterpenos Policíclicos/análise , Sesquiterpenos/análise , Sesquiterpenos/químicaRESUMO
The effect of exogenous application of jasmonic acid (JA) on the concentration of main terpenes and density of glandular trichomes was investigated in the Mexican oregano, propagated from seeds from 3 localities. JA 1 mM was applied locally and to the whole plant. JA locally applied increased the number of trichomes, with a mean of 20 trichomes more with respect to the controls in plants from Tecomavaca and Zapotitlán Salinas, and significantly increased the thymol concentration by 185% systemically and 255% locally, compared to the control. JA applied to the whole plant decreased the number of trichomes and increased the concentration of caryophyllene from 0.79 to 1.7 mg g-1, and α-caryophyllene from 0.3 to 0.8 mg g-1 in plants from San Rafael with reference to water control. The results suggest a plasticity of morphologic and phytochemical responses, and a potential use of JA to improve phenolic monoterpenes and sesquiterpenes production.
Assuntos
Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Terpenos/análise , Tricomas/efeitos dos fármacos , Verbenaceae/efeitos dos fármacos , Lippia , México , Sesquiterpenos Monocíclicos , Monoterpenos/análise , Origanum/efeitos dos fármacos , Sesquiterpenos Policíclicos/análise , Timol/análiseRESUMO
(-)-α-Bisabolol (BISA) is an unsaturated monocyclic sesquiterpenes compound, mainly found in the essential oil of chamomile (Matricaria chamomilla). It has been reported that this compound has several biological activities, but there are few studies evaluating the activity of this compound in the systemic inflammatory response in infectious processes. The aim of this study was to evaluate the effect of BISA on the inflammatory response and survival rate in a systemic infection model, and in vitro neutrophils phagocytic activity. BISA at concentration of 3, 10, 30, and 90 µg/ml did not presented in vitro cytotoxicity in MTT assay, and at concentrations of 1 and 3 µg/ml the BISA treatment increased in vitro phagocytic neutrophil activity. For the inflammatory response study, we verified the BISA treatment effect in a cecal ligation and puncture (CLP)-induced systemic infection model in mice; in this model, we demonstrate that BISA at dose of 100 mg/kg reduced the leukocyte recruitment in peritoneal cavity; at dose of 200 mg/kg, the NO concentration was increased in the peritoneal cavity. The bacteria CFU number was reduced in mice blood in the BISA treatment, at doses of 100 and 200 mg/kg. The BISA treatment at doses of 50 and 100 mg/kg increased the myeloperoxidase activity and reduction NO production in lung tissue of mice in CLP model. At dose of 100 mg/kg, the BISA treatment was able to reduce the mortality rate of mice submitted to CLP-induced sepsis and observed for 7 days. The results suggest an effect of BISA on inflammatory response, with activity on leukocyte chemotactic and NO production, in addition to increasing the survival rate of animals submitted to CLP model.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Sesquiterpenos Monocíclicos/farmacologia , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Carga Bacteriana , Células Cultivadas , Quimiotaxia de Leucócito/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Patógeno , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/microbiologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/microbiologia , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Óxido Nítrico/metabolismo , Peritônio/efeitos dos fármacos , Peritônio/imunologia , Peritônio/metabolismo , Peritônio/microbiologia , Sepse/imunologia , Sepse/metabolismo , Sepse/microbiologiaRESUMO
Abstract This study evaluated the antibacterial and antiproliferative activities of the essential oil of Psidium guajava leaves (PG-EO), traditionally used in folk medicine. The essential oil was obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. The major PG-EO chemical constituents were identified by GC-MS and GC-FID as being β-caryophyllene (16.1%), α-humulene (11.9%), aromadendrene oxide (14.7%), δ-selinene (13.6%), and selin-11-en-4α-ol (12.5%). The antibacterial activity of the essential oil of P. guajava leaves was determined in terms of its minimum inhibitory concentrations (MIC) using the broth microdilution method in 96-well microplates. PG-EO had moderate activity against Streptococcus mutans (MIC = 200 µg/mL), S. mitis (MIC = 200 µg/mL), S. sanguinis (MIC = 400 µg/mL), S. sobrinus (MIC = 100 µg/mL), and S. salivarius (MIC = 200 µg/mL). The antiproliferative activity was evaluated against different tumor cell lines: breast adenocarcinoma (MCF-7), human cervical adenocarcinoma (HeLa), and human gliobastoma (M059J). A normal human cell line (GM07492A, lung fibroblasts) was included. The antiproliferative activity was evaluated using the XTT assay and the results were expressed as IC50. The essential oil showed significantly lower IC50 values against MCF-7 and M059J lines than that obtained for the normal line, showing selectivity. Our results suggest that the essential oil of Psidium guajava L. has promising biological activities and can be considered a new source of bioactive compounds.
Resumo Este estudo avaliou as atividades antibacteriana e antiproliferativa do óleo essencial das folhas frescas de Psidium guajava (PG-OE), tradicionalmente utilizadas na medicina popular. O óleo essencial foi obtido por hidrodestilação das folhas frescas, utilizando aparelho do tipo Clevenger. Os principais constituintes químicos de PG-OE identificados por CG-EM e CG-DIC foram: β-cariofileno (16,1%), α-humuleno (11,9%), óxido de aromadendreno (14,7%), δ-selineno (13,6%) e selin-11-en-4α-ol (12,5%). A atividade antibacteriana do óleo essencial das folhas de P. guajava foi determinada em termo de sua concentração inibitória mínima (CIM) utilizando o método de microdiluição de caldo em microplacas de 96 poços. PG-OE apresentou moderada atividade contra Streptococcus mutans (CIM = 200 μg/mL), S. mitis (CIM = 200 μg/mL), S. sanguinis (CIM = 400 μg/mL), S. sobrinus (CIM = 100 μg/mL) e S. salivarius (CIM = 200 μg/mL). A atividade antiproliferativa foi avaliada frente a diferentes linhagens de células tumorais como: adenocarcinoma de mama (MCF-7), adenocarcinoma cervical humano (HeLa) e gliobastoma humano (M059J). Foi incluída uma linhagem celular humana normal (GM07492A, fibroblastos pulmonares). A atividade antiproliferativa foi avaliada utilizando o ensaio XTT e os resultados foram expressos como CI50. As linhagens MCF-7 e M059J mostraram valores significativamente mais baixos de CI50 do que os obtidos para a linhagem normal, mostrando seletividade. Nossos resultados sugerem que o óleo essencial das folhas frescas de Psidium guajava L. possui atividades biológicas promissoras e pode ser considerado como uma nova fonte de compostos bioativos.
Assuntos
Humanos , Folhas de Planta , Psidium , Proliferação de Células/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Antibacterianos/farmacologia , Sesquiterpenos/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Testes de Sensibilidade Microbiana , Azulenos/farmacologia , Sesquiterpenos Monocíclicos , Sesquiterpenos Policíclicos , Cromatografia Gasosa-Espectrometria de MassasRESUMO
Chronic pain is a continuous or recurring pain which exceeds the normal course of recovery to an injury or disease. According to the origin of the chronic pain, it can be classified as inflammatory or neuropathic. This study aimed to evaluate the antinociceptive and anti-inflammatory effect of (-)-α-bisabolol (BIS) alone and complexed with ß-cyclodextrin (ßCD) in preclinical models of chronic pain. Chronic pain was induced by Freund's Complete Adjuvant (FCA) or partial lesion of the sciatic nerve (PLSN). Swiss mice were treated with BIS, BIS-ßCD (50â¯mg/kg, p.o) or vehicle (control) and mechanical hyperalgesia, thermal hyperalgesia, muscle strength and motor coordination were evaluated. In addition, levels of TNF-α and IL-10 and expression of the ionized calcium-binding adapter protein (IBA-1) were assessed in the spinal cord of the mice. The complexation efficiency of BIS in ßCD was evaluated by High-Performance Liquid Chromatography. BIS and BIS-ßCD reduced (pâ¯<â¯0.001) mechanical and thermal hyperalgesia. No alterations were found in force and motor coordination. In addition, BIS and BIS-ßCD inhibited (pâ¯<â¯0.05) TNF-α production in the spinal cord and stimulated (pâ¯<â¯0.05) the release of IL-10 in the spinal cord in PLSN-mice. Further, BIS and BIS-ßCD reduced IBA-1 immunostaining. Therefore, BIS and BIS-ßCD attenuated hyperalgesia, deregulated cytokine release and inhibited IBA-1 expression in the spinal cord in the PLSN model. Moreover, our results show that the complexation of BIS in ßCD reduced the therapeutic dose of BIS. We conclude that BIS is a promising molecule for the treatment of chronic pain.