RESUMEN
The Ocimum species present active compounds with the potential to develop drugs for treating chronic disease conditions, such as anxiety and seizures. The present study aims to investigate the anticonvulsant and anxiolytic-like effect of the essential oil from O. basilicum Linn (OEFOb) leaves and its major constituent estragole (ES) in vivo on adult zebrafish (aZF) and in silico. The aZF were treated with OEFOb or ES or vehicle and submitted to the tests of toxicity, open-field, anxiety, and convulsion and validated the interactions of the estragole on the involvement of GABAergic and serotonergic receptors by molecular docking assay. The results showed that the oral administration of OEFOb and ES did not have a toxic effect on the aZF and showed anxiolytic-like effects with the involvement of GABAA, 5-HT1, 5-HT2A/2C and 5-HT3A/3B as well on anxiety induced by alcohol withdrawal. The OEFOb and ES showed anticonvulsant potential attenuating the seizures induced by pentylenetetrazole (PTZ) by modulation of the GABAA system. Both anxiolytic and anticonvulsant effects were corroborated by the potential of the interaction of ES by in silico assay. These study samples demonstrate the pharmacological evidence and potential for using these compounds to develop new anxiolytic and anticonvulsant drugs.
Asunto(s)
Derivados de Alilbenceno , Anisoles , Ansiolíticos , Anticonvulsivantes , Ocimum basilicum , Aceites Volátiles , Hojas de la Planta , Convulsiones , Pez Cebra , Animales , Ansiolíticos/farmacología , Ansiolíticos/química , Ansiolíticos/aislamiento & purificación , Anticonvulsivantes/farmacología , Anticonvulsivantes/química , Anticonvulsivantes/aislamiento & purificación , Aceites Volátiles/farmacología , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/química , Hojas de la Planta/química , Ocimum basilicum/química , Anisoles/farmacología , Anisoles/aislamiento & purificación , Derivados de Alilbenceno/farmacología , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Simulación del Acoplamiento Molecular , Ansiedad/tratamiento farmacológico , Masculino , Pentilenotetrazol/toxicidadRESUMEN
This study determined chemical profiles, antibacterial and antibiofilm activities of the essential oils (EOs) obtained by A. visnaga aerial parts and F. vulgare fruits. Butanoic acid, 2-methyl-, 3-methylbutyl ester (38.8%), linalyl propionate (34.7%) and limonene (8.5%) resulted as main constituents of A. visnaga EO. In F. vulgare EO trans-anethole (76.9%) and fenchone (14.1%) resulted as main components. The two EOs were active against five bacterial strains (Acinetobacter baumannii, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus) at different degrees. The MIC values ranged from 5 ± 2 to 10 ± 2 µL/mL except for S. aureus (MIC >20 µL/mL). EOs exhibited inhibitory effect on the formation of biofilm up to 53.56 and 48.04% against E. coli and A. baumannii, respectively and activity against bacterial metabolism against A. baumannii and E. coli, with biofilm-inhibition ranging from 61.73 to 73.55%. The binding affinity of the identified components was estimated by docking them into the binding site of S. aureus gyrase (PDB code 2XCT) and S. aureus tyrosyl-tRNA synthetase (PDB code 1JIJ). trans-Anethole and butanoic acid, 2-methyl-, 3-methylbutyl ester showed relatively moderate binding interactions with the amino acid residues of S. aureus tyrosyl-tRNA synthetase. In addition, almost all predicted compounds possess good pharmacokinetic properties with no toxicity, being inactive for cytotoxicity, carcinogenicity, hepatotoxicity, mutagenicity and immunotoxicity parameters. The results encourage the use of these EOs as natural antibacterial agents in food and pharmaceutical industries.
Asunto(s)
Derivados de Alilbenceno , Antibacterianos , Biopelículas , Foeniculum , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Aceites Volátiles , Biopelículas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Aceites Volátiles/farmacología , Aceites Volátiles/química , Foeniculum/química , Myrtaceae/química , Frutas/química , Anisoles/farmacología , Anisoles/química , Anisoles/aislamiento & purificación , Componentes Aéreos de las Plantas/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/química , Canfanos , NorbornanosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: India's ancient texts, the Charak Samhita and Sushruta Samhita, make reference to the traditional medicinal usage of Acorus calamus L. In India and China, it has long been used to cure stomach aches, cuts, diarrhea, and skin conditions. This ability of the rhizome is attributed to its antimicrobial properties. Research studies to date have shown its antimicrobial properties. However, scientific evidence on its mode of action is still lacking. AIM OF THE STUDY: Acorus calamus L. rhizome extract and its bioactive fraction exhibits antibacterial effect by modulating membrane permeability and fatty acid composition. MATERIAL AND METHOD: The secondary metabolites in the rhizome of A. calamus L. were extracted in hexane using Soxhlet apparatus. The ability of the extract to inhibit multidrug resistant bacterial isolates, namely Bacillus cereus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were evaluated using checkerboard assay. Further, the extract was purified using thin layer chromatography, gravity column chromatography, and combiflash chromatography. Structure elucidation of the active compound was done using GC-MS, FT-IR, and UV-Vis spectral scan. The mode of action of the bioactive fraction was determined. Bacterial membrane damage was analyzed using SEM, membrane permeability was determined using SYBR green I and PI dye, leakage of cytoplasmic contents were analyzed using Bradford assay and Fehling's reagent. The ability to inhibit efflux pump of A. baumannii was determined using EtBr accumulation assay and ß-lactamase inhibition was analyzed using nitrocefin as substrate. Also, the biofilm inhibition of B. cereus was determined using crystal violet dye. Moreover, the effect of the bioactive fraction on the fatty acid profile of the bacterial membrane was determined by GC-FAME analysis using 37 component FAME mix as standard. RESULTS: Acorus calamus L. rhizome hexane extract (AC-R-H) demonstrated broad-spectrum antibacterial activity against all the isolates tested. AC-R-H extract also significantly reduced the MIC of ampicillin against all tested bacteria, indicating its bacterial resistance modulating properties. The assay guided purification determined Asarone as the major compound present in the bioactive fraction (S-III-BAF). S-III-BAF was found to reduce the MIC of ampicillin against Escherichia coli (100-25 mg/mL), Pseudomonas aeruginosa (15-3.25 mg/mL), Acinetobacter baumannii (12.5-1.56 mg/ml), and Bacillus cereus (10-1.25 mg/mL). Further, it recorded synergistic activity with ampicillin against B. cereus (FICI = 0.365), P. aeruginosa (FICI = 0.456), and A. baumannii (FICI = 0.245). The mode of action of S-III-BAF can be attributed to its ability to disturb the membrane integrity, enhance membrane permeability, reduce biofilm formation, and possibly alter the fatty acid composition of the bacterial cell membranes. CONCLUSION: The bioactive fraction of AC-R-H extract containing Asarone as the active compound showed antibacterial activity and synergistic interactions with ampicillin against the tested bacterial isolates. Such activity can be attributed to the modulation of fatty acids present in bacterial membranes, which enhances membrane permeability and causes membrane damage.
Asunto(s)
Acorus , Antibacterianos , Permeabilidad de la Membrana Celular , Ácidos Grasos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Rizoma , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/química , Rizoma/química , Acorus/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Permeabilidad de la Membrana Celular/efectos de los fármacos , Ácidos Grasos/farmacología , Ácidos Grasos/química , Derivados de Alilbenceno , Anisoles/farmacología , Anisoles/aislamiento & purificación , Anisoles/químicaRESUMEN
Hedyosmum racemosum (Ruiz & Pav.) G. is a native species of Ecuador used in traditional medicine for treatment of rheumatism, bronchitis, cold, cough, asthma, bone pain, and stomach pain. In this study, fresh H. racemosum leaves of male and female specimens were collected and subjected to hydrodistillation for the extraction of the essential oil. The chemical composition of male and female essential oil was determined by gas chromatography-gas chromatography equipped with a flame ionization detector and coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against five Gram-positive and two Gram-negative bacteria, and two dermatophytes fungi. The scavenging radical properties of the essential oil were evaluated by DPPH and ABTS assays. The chemical analysis allowed us to identify forty-three compounds that represent more than 98% of the total composition. In the non-polar and polar column, α-phellandrene was the principal constituent in male (28.24 and 25.90%) and female (26.47 and 23.90%) essential oil. Other main compounds were methyl chavicol, germacrene D, methyl eugenol, and α-pinene. Female essential oil presented a strong activity against Klebsiella pneumoniae (ATCC 9997) with an minimum inhibitory concentration (MIC) of 500 µg/mL and a scavenging capacity SC50 of 800 µg/mL.
Asunto(s)
Antibacterianos/química , Antioxidantes/química , Monoterpenos Ciclohexánicos/química , Magnoliopsida/química , Aceites Volátiles/química , Derivados de Alilbenceno/química , Derivados de Alilbenceno/aislamiento & purificación , Anisoles/química , Anisoles/aislamiento & purificación , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Arthrodermataceae/efectos de los fármacos , Arthrodermataceae/crecimiento & desarrollo , Benzotiazoles/antagonistas & inhibidores , Monoterpenos Bicíclicos/química , Monoterpenos Bicíclicos/aislamiento & purificación , Compuestos de Bifenilo/antagonistas & inhibidores , Monoterpenos Ciclohexánicos/aislamiento & purificación , Ecuador , Eugenol/análogos & derivados , Eugenol/química , Eugenol/aislamiento & purificación , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/crecimiento & desarrollo , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/crecimiento & desarrollo , Humanos , Magnoliopsida/metabolismo , Masculino , Pruebas de Sensibilidad Microbiana , Picratos/antagonistas & inhibidores , Hojas de la Planta/química , Plantas Medicinales , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/aislamiento & purificación , Factores Sexuales , Ácidos Sulfónicos/antagonistas & inhibidoresRESUMEN
Acorus tatarinowii Schott is a traditional Chinese medicine used to treat memory and cognitive dysfunction. Because of their efficacy and lower toxic effects, research on α- and ß-asarone, the phytoconstituents, has attracted attention owing to their remarkable pharmacological activities. Silver ion coordination complexation high-speed counter-current chromatography was used to separate these isomers from A. tatarinowii extract, coupled with accelerated solvent extraction. Accelerated solvent extraction parameters were investigated with single-factor and orthogonal testing. A two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:1:2:1, v/v) with 0.50 mol/L silver ions was selected for separation. From 2.0 g crude extract, 1.4 g of ß-asarone and 0.09 g of α-asarone were obtained with purities over 98% by sequential sample loading in 20 h. The isolated compounds were identified by electrospray ionization mass spectrometry, 1H and 13C NMR. Silver ions significantly increased the separation factor and retention of the stationary phase. The chromatographic behavior indicated that cis-configuration was more strongly complexed with the silver ion. This was further demonstrated with the help of computational analysis. In conclusion, the established method could be employed to separate other cis-trans or E/Z isomers that form coordination complexes.
Asunto(s)
Acorus/química , Anisoles/análisis , Distribución en Contracorriente/métodos , Acorus/metabolismo , Derivados de Alilbenceno , Anisoles/aislamiento & purificación , Teoría Funcional de la Densidad , Isomerismo , Extracción Líquido-Líquido , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Plata/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
The UV absorption spectra of six structurally related derivatives of anisole and veratrole, i.e., anisaldehyde, (E)-anethole, estragole, veratraldehyde, methyleugenol and (E)-methylisoeugenol, were recorded at various concentrations of the anionic surfactants, either sodium lauryl sulfate (SLS) or sodium lauryl ether sulfate (SLES) at T = 298 K. In addition, conductivity and density measurements were made for the SLS and SLES solutions to determine the volumetric properties of the studied surfactants. Next, using the W. Al-Soufi, L. Pineiro and M. Novo model (APN model) including the pseudo-phase model for micellar solubilization, the values of micelle-water partition coefficients for each perfume-surfactant system were determined. In addition, the relations between the molecular structures of the solute and the head group of the surfactant and the value of the micelle-water partition coefficient as well as the octanol-water one were discussed.
Asunto(s)
Anisoles/química , Aniones , Anisoles/aislamiento & purificación , Micelas , Perfumes/química , Dodecil Sulfato de Sodio/análogos & derivados , Dodecil Sulfato de Sodio/química , Solubilidad , Soluciones , Espectrofotometría Ultravioleta , Tensoactivos/química , AguaRESUMEN
The present study reports the evaluation of hexane extract from Endlicheria paniculata and its main metabolite dehydrodieugenol B in the inflammatory response induced by a murine implant sponge model. As a result, a reduction in the inflammatory markers (myeloperoxidase and N-acetyl-ß-D-glucosaminidase) and number of mast cells were observed in comparison to the control group. All doses were also able to reduce angiogenic parameters evaluated in fibrovascular tissue. In implants treated with dehydrodieugenol B a reduction in total collagen deposition and types I and III collagen fibers were observed, while an increased in total collagen deposition and types I and III collagen fibers were observed in the treatment with hexane extract. Docking studies into cyclooxygenase-2 active site revealed that the dehydrodieugenol B had binding modes and energies comparable with celecoxib, diclofenac and ibuprofen. Therefore, dehydrodieugenol B was able to alter key components of chronic inflammation, resulting in a reduced inflammatory response and also presenting antifibrogenic and antiangiogenic effects. However, treatment with hexane extract resulted in a reduced inflammatory response with antiangiogenic effects, but caused fibrogenic effects.
Asunto(s)
Anisoles/farmacología , Antiinflamatorios/farmacología , Antifibrinolíticos/farmacología , Lauraceae/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Inhibidores de la Angiogénesis/farmacología , Animales , Anisoles/aislamiento & purificación , Antiinflamatorios/aislamiento & purificación , Antifibrinolíticos/aislamiento & purificación , Brasil , Colágeno/metabolismo , Hexanos , Inflamación/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Hojas de la Planta/químicaRESUMEN
The volatile components produced by Leptolejeunea elliptica (Lejeuneaceae), which is a liverwort grown on the leaves of tea (Camellia sinensis), were collected and analyzed using headspace solid-phase microextraction-gas chromatography/mass spectrometry (HS-SPME-GC/MS). 1-Ethyl-4-methoxybenzene (1), 1-ethyl-4-hydroxybenzene (2), and 1-acetoxy-4-ethylbenzene (3) were identified as the major components together with several other phenolic compounds, including 1,2-dimethoxy-4-ethylbenzene, and 4-ethylguaiacol in addition to sesquiterpene hydrocarbons, such as α-selinene, ß-selinene, ß-elemene, and ß-caryophyllene. GC/Olfactometry showed the presence of linalool, acetic acid, isovaleric acid, trans-methyl cinnamate, and trans-4,5-epoxy-(2E)-decenal, as the volatile components produced by L. elliptica.
Asunto(s)
Hepatophyta/metabolismo , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/aislamiento & purificación , Ácido Acético/análisis , Ácido Acético/aislamiento & purificación , Anisoles/análisis , Anisoles/aislamiento & purificación , Derivados del Benceno/análisis , Derivados del Benceno/aislamiento & purificación , Camellia sinensis , Cromatografía de Gases y Espectrometría de Masas/métodos , Japón , Olfatometría , Fenol/análisis , Fenol/aislamiento & purificación , Fenoles/análisis , Fenoles/aislamiento & purificación , Sesquiterpenos Policíclicos/análisis , Sesquiterpenos Policíclicos/aislamiento & purificación , Sesquiterpenos/análisis , Sesquiterpenos/aislamiento & purificación , Microextracción en Fase Sólida/métodosRESUMEN
Phenylpropanoids comprise a broad spectrum of biologically active natural products. As part of our ongoing research on antiepileptic active compounds from traditional Chinese herb, Acorus calamus var. angustatus Besser, three undescribed phenylpropanoids and twenty-two known ones were isolated. All the undescribed structures were determined by a combination of 1D and 2D NMR, HRMS. In addition, γ-asaronol was identified as racemates and its absolute configuration were determined by the modified Mosher's method and ECD spectral data. Furthermore, some selected isolated compounds were evaluated for their cell viability and neuroprotective activities in H2O2-induced SH-SY5Y cells. α-Asaronol, ß-asaronol, 3-(2,4,5-trimethoxyphenyl)propan-1-ol and 1,2,4-trimethoxy-5-(3-methoxypropyl)benzene exerted potential protective activity from neuronal oxidative stress in all test concentrations ranging from 0.01 to 100 µM, in which the neuroprotective activity of ß-asaronol was the best.
Asunto(s)
Acorus/química , Anisoles/farmacología , Fármacos Neuroprotectores/farmacología , Fenilpropionatos/farmacología , Fitoquímicos/farmacología , Rizoma/química , Derivados de Alilbenceno , Anisoles/química , Anisoles/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/farmacología , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Fenilpropionatos/química , Fenilpropionatos/aislamiento & purificación , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Alzheimer's disease (AD) is a progressive, neurodegenerative brain disorder associated with loss of memory and cognitive function. Beta-amyloid (Aß) aggregates, in particular, are known to be highly neurotoxic and lead to neurodegeneration. Therefore, blockade or reduction of Aß aggregation is a promising therapeutic approach in AD. We have previously reported an inhibitory effect of the methanol extract of Perilla frutescens (L.) Britton (Lamiaceae) and its hexane fraction on Aß aggregation. Here, the hexane fraction of P. frutescens was subjected to diverse column chromatography based on activity-guided isolation methodology. This approach identified five asarone derivatives including 2,3-dimethoxy-5-(1E)-1-propen-1-yl-phenol (1), ß-asarone (2), 3-(2,4,5-trimethoxyphenyl)-(2E)-2-propen-1-ol (3), asaronealdehyde (4), and α-asarone (5). All five asarone derivatives efficiently reduced the aggregation of Aß and disaggregated preformed Aß aggregates in a dose-dependent manner as determined by a Thioflavin T (ThT) fluorescence assay. Furthermore, asarone derivatives protected PC12 cells from Aß aggregate-induced toxicity by reducing the aggregation of Aß, and significantly reduced NO production from LPS-stimulated BV2 microglial cells. Taken together, these results suggest that asarone derivatives derived from P. frutescens are neuroprotective and have the prophylactic and therapeutic potential in AD.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/antagonistas & inhibidores , Anisoles/química , Agregación Patológica de Proteínas/tratamiento farmacológico , Derivados de Alilbenceno , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/química , Animales , Anisoles/aislamiento & purificación , Humanos , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Células PC12 , Perilla frutescens/química , Hojas de la Planta/química , Agregación Patológica de Proteínas/patología , RatasRESUMEN
Piper cubeba L. is the berry of a shrub that is indigenous to Java, Southern Borneo, Sumatra, and other islands in the Indian Ocean. The plant is usually used in folk traditional medicine and is an important ingredient in cooking. The purpose of this study was to isolate and purify the bioactive compounds from P. cubeba L. fractions. In addition, the isolated compounds were tested for their antibacterial and antispore activities against vegetative cells and spores of Bacillus cereus ATCC33019, B. subtilis ATCC6633, B. pumilus ATCC14884, and B. megaterium ATCC14581. The phytochemical investigation of the DCM fraction yielded two known compounds: ß-asarone (1), and asaronaldehyde (2) were successfully isolated and identified from the methanol extract and its fractions of P. cubeba L. Results showed that exposing the vegetative cells of Bacillus sp. to isolated compounds resulted in an inhibition zone with a large diameter ranging between 7.21 to 9.61 mm. The range of the minimum inhibitory concentration (MIC) was between 63.0 to 125.0 µg/mL and had minimum bactericidal concentration (MBC) at 250.0 to 500.0 µg/mL against Bacillus sp. Isolated compounds at a concentration of 0.05% inactivated more than 3-Log10 (90.99%) of the spores of Bacillus sp. after an incubation period of four hours, and all the spores were killed at a concentration of 0.1%. The structures were recognizably elucidated based on 1D and 2D-NMR analyses (1H, 13C, COSY, HSQC, and HMBC) and mass spectrometry data. Compounds 1, and 2 were isolated for the first time from this plant. In conclusion, the two compounds show a promising potential of antibacterial and sporicidal activities against Bacillus sp. and thus can be developed as an anti-Bacillus agent.
Asunto(s)
Aldehídos/farmacología , Anisoles/farmacología , Antibacterianos/farmacología , Piper/química , Esporas Bacterianas/efectos de los fármacos , Aldehídos/aislamiento & purificación , Derivados de Alilbenceno , Anisoles/aislamiento & purificación , Antibacterianos/aislamiento & purificación , Bacillus cereus/efectos de los fármacos , Bacillus cereus/fisiología , Bacillus megaterium/química , Bacillus megaterium/efectos de los fármacos , Bacillus pumilus/efectos de los fármacos , Bacillus pumilus/fisiología , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/fisiología , Cromatografía en Capa Delgada , Medicina Tradicional , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
Acori Tatarinowii Rhizoma (ATR, the dried rhizome of Acorus tatarinowii Schott.) is a traditional Chinese medicine widely used to treat brain diseases, e.g. depression, forgetfulness, anxiety and epilepsy. Several lines of evidence support that ATR has neuronal beneficial functions in animal models, but its action mechanism in cellular level is unknown. Here, we identified α-asarone and ß-asarone could be the major active ingredients of ATR, which, when applied onto cultured rat astrocytes, significantly stimulated the expression and secretion of neurotrophic factors, i.e. nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF), in dose-dependent manners. These results suggested that the neuronal action of ATR, triggered by asarone, might be mediated by an increase of expression of neurotrophic factors in astrocytes, which therefore could support the clinical usage of ATR. In addition, application of PKA inhibitor, H89, in cultured astrocytes partially blocked the asarone-induced neurotrophic factor expression, suggesting the involvement of PKA signaling. The results proposed that α-asarone and ß-asarone from ATR could serve as potential candidates for drug development in neurodegenerative diseases.
Asunto(s)
Acorus/química , Anisoles/farmacología , Astrocitos/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Factores de Crecimiento Nervioso/metabolismo , Derivados de Alilbenceno , Animales , Anisoles/aislamiento & purificación , Astrocitos/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Células Cultivadas , Expresión Génica , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Ratas Sprague-Dawley , Rizoma/químicaRESUMEN
Leishmaniasis is a neglected disease that affects more than 12 million people, with a limited therapy. Plant-derived natural products represent a useful source of anti-protozoan prototypes. In this work, four derivatives were prepared from neolignans isolated from the Brazilian plant Nectandra leucantha, and their effects against intracellular amastigotes of Leishmania (L.) infantum evaluated in vitro. IC50 values between 6 and 35 µM were observed and in silico predictions suggested good oral bioavailability, no PAINS similarities, and ADMET risks typical of lipophilic compounds. The most selective (SI > 32) compound was chosen for lethal action and immunomodulatory studies. This compound caused a transient depolarization of the plasma membrane potential and induced an imbalance of intracellular Ca2+, possibly resulting in a mitochondrial impairment and leading to a strong depolarization of the membrane potential and decrease of ATP levels. The derivative also interfered with the cell cycle of Leishmania, inducing a programmed cell death-like mechanism and affecting DNA replication. Further immunomodulatory studies demonstrated that the compound eliminates amastigotes via an independent activation of the host cell, with decrease levels of IL-10, TNF and MCP-1. Additionally, this derivative caused no hemolytic effects in murine erythrocytes and could be considered promising for future lead studies.
Asunto(s)
Anisoles/farmacología , Antiprotozoarios/farmacología , Leishmania infantum/efectos de los fármacos , Leishmaniasis/tratamiento farmacológico , Enfermedades Desatendidas/tratamiento farmacológico , Animales , Anisoles/química , Anisoles/aislamiento & purificación , Anisoles/uso terapéutico , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/uso terapéutico , Brasil , División Celular/efectos de los fármacos , Línea Celular , Replicación del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Metabolismo Energético/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Lauraceae/química , Leishmania infantum/citología , Leishmania infantum/genética , Leishmania infantum/metabolismo , Leishmaniasis/parasitología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mesocricetus , Ratones , Enfermedades Desatendidas/parasitología , Cultivo Primario de Células , Especies Reactivas de Oxígeno , Pruebas de ToxicidadRESUMEN
BACKGROUND: Microsporum spp. are keratinophilic dermatophytes that mainly invade the stratum corneum of the skin and hair causing clinical symptoms associated with tinea. Its treatment has several limitations, and the search for new active molecules is necessary. OBJECTIVE: To evaluate the antifungal and cytotoxic potential of Eugenia caryophyllus essential oil (EO), eugenol, isoeugenol and methylisoeugenol against Microsporum canis, M. gypseum and Vero cells. METHODS: The EO was extracted by conventional heating-assisted hydrodistillation, the eugenol obtained commercially and the derivatives through Williamson synthesis. Minimal inhibitory concentration (MICs), minimum fungicidal concentration, inhibition of radial mycelial growth and germination inhibition were used to evaluate the antifungal activity. In addition, a colorimetric test was conducted to evaluate cytotoxic activity. RESULTS: MIC and MFC values for all compounds were 62.5-500 µg/mL for both of the species of Microsporum evaluated. Also, concentrations of 300 µg/mL of the compounds inhibited 100% of M. canis mycelium. The inhibition of germination was observed after 6 hours of treatment (11.86 ± 3.46-85.31 ± 0%). No cytotoxicity was observed in Vero cells (CC50 > 105 µg/mL), whereas terbinafine showed CC50 31.00 ± 0.61 µg/mL. CONCLUSIONS: Our study indicates an interesting bioactivity of isoeugenol and methylisoeugenol against M. canis, M. gypseum and mammalian cells.
Asunto(s)
Antifúngicos/farmacología , Eugenol/farmacología , Microsporum/efectos de los fármacos , Aceites Volátiles/farmacología , Syzygium/química , Animales , Anisoles/aislamiento & purificación , Anisoles/farmacología , Anisoles/toxicidad , Antifúngicos/aislamiento & purificación , Antifúngicos/toxicidad , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Eugenol/análogos & derivados , Eugenol/aislamiento & purificación , Eugenol/toxicidad , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Aceites Volátiles/aislamiento & purificación , Células VeroRESUMEN
In order to determine the morphophysiological and phytochemical properties of various Ducrosia anethifolia populations, the plant samples were collected from 20 locations in native regions. Current study indicated significant differences in the morphophysiological and phytochemical characteristics of D. anethifolia populations collected from 20 locations in Sistan and Baluchestan Province, Iran. The highest value of plant height and the number of lateral stems, node per plant, umbellate per umbel, seeds per umbellate and the roots fresh and dry weight were related to the location with relatively high rainfall (130-161â mm) and low altitude (up to 1165â m) compared with others. Based on the essential oil components, D. anethifolia populations were divided into five different chemotypes. Chemotypes I, II and III were characterized by high amounts of methyl chavicol, chrysanthenyl acetate and decanal, respectively. Moreover, the populations with high amounts of decanal, anethole and dodecanal were placed in chemotype IV. Chemotype V was attributed to the Naserabad population with 1-decanol as the major compound.
Asunto(s)
Apiaceae/química , Fitoquímicos/química , Derivados de Alilbenceno , Anisoles/análisis , Anisoles/aislamiento & purificación , Apiaceae/metabolismo , Compuestos Bicíclicos con Puentes/análisis , Compuestos Bicíclicos con Puentes/aislamiento & purificación , Ecosistema , Cromatografía de Gases y Espectrometría de Masas , Irán , Monoterpenos/análisis , Monoterpenos/aislamiento & purificación , Aceites Volátiles/química , Fitoquímicos/análisis , Fitoquímicos/aislamiento & purificación , Análisis de Componente PrincipalRESUMEN
A new asarone-derived racemate (1) was isolated from the rhizome of Acorus tatarinowii. The structure of 1 was established by comprehensive spectroscopic analyses, and it was successfully resolved by chiral HPLC, demonstrating that it is racemic. The absolute configurations of 1a [(-)-acortatarone A] and 1b [(+)-acortatarone A] were determined using quantum chemical calculations. Compounds 1a and 1b were the first cases of asarone derivatives with the 5,7-dialkyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one core. The α-glucosidase inhibitory and acetylcholinesterase (AChE) inhibitory activities of 1 were evaluated, and it exhibited α-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).
Asunto(s)
Acorus/química , Anisoles/química , Inhibidores de Glicósido Hidrolasas/química , Rizoma/química , Acetilcolinesterasa/metabolismo , Derivados de Alilbenceno , Anisoles/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Estructura Molecular , alfa-Glucosidasas/metabolismoRESUMEN
Response surface methodology (RSM), based on a central composite design, was used to determine the best liquid-to-raw material ratio (10:3-15 mL/g), extraction time (1-3 h), and ethanol concentration (50%-100%) for maximum content of α-asarone from Perilla frutescens (PF) extract. Experimental values of α-asarone were 9.51-46.36 mg/g; the results fitted a second-order quadratic polynomial model and correlated with the proposed model (R2 > 0.9354). The best conditions were obtained with extraction time of 1.76 h, liquid-to-raw material ratio of 10:13.5 mL/g, and ethanol concentration of 90.37%. Under these conditions, the model predicted extraction content of 40.56 mg/g, while experimental PF content of α-asarone was 43.84 mg/g dried plant. Optimized conditions determined for maximum content of α-asarone were similar to the experimental range. Experimental values agreed with those predicted, thus validating and indicating suitability of both the model and the RSM approach for optimizing extraction conditions. In addition, a reliable, reproducible and accurate method for the quantitative determination of α-asarone by High Performance Liquid Chromatography (HPLC) analysis was developed with limit of detection (LOD), limit of quantitation (LOQ) values of 0.10 and 0.29 µg/mL and excellent linearity (R2 > 0.9999).
Asunto(s)
Anisoles/aislamiento & purificación , Perilla frutescens/química , Extractos Vegetales/aislamiento & purificación , Derivados de Alilbenceno , Cromatografía Líquida de Alta Presión , Etanol/química , Límite de Detección , Solventes/químicaRESUMEN
Virola species have been used in traditional medicine as healing in skin infections. From V. surinanensis oil were isolated several sesquiterpene as the nerolidol which showed activity against species of Leishmania. The current study aimed to evaluate the leishmanicide activity and toxicity of extracts, fractions and surinamesin obtained from leaves of Virola surinamensis. Hexane, Ethyl Acetate, and Methanol extracts were obtained from powder of dry leaves of V. surinamensis. The hexane and ethyl acetate extracts were fractionated by silica gel column chromatography and increasingly polar gradient. The viability of L. chagasi and L. amazonensis promastigotes was assessed by tetrazolium salt assay (MTT). Peritoneal macrophages were exposed to L. amazonensis promastigotes. The treatment was performed with the extracts for 24 h. Then, the coverslips were stained and the infection index was determined. Cytotoxicity was determined in macrophage cells by peritoneum viability assay (MTT). The selectivity index was calculated as the product of cytotoxic concentration 50% and inhibitory concentration 50%. The hexane extract showed leishmanicide activity in promastigotes. The ethyl acetate, methanol extracts and fractions (C1-C6), were inactive against promastigote form of L. chagasi and L. amzazonensis. None extract showed effect on L. amazonensis amastigotes. All samples tested showed low cytotoxicity (CC50 > 500 µg/mL). The selectivity index of the hexane extract was greater than 5. The hexane extract of V. surinamensis was active against L. chagasi and L. amazonensis promastigotes. The extract fractionation did not increase significantly its antipromastigote activity. The surinamensin is probably not responsible for the activity. The extracts were inactive against amastigotes of L. amazonensis.
Asunto(s)
Antiprotozoarios/farmacología , Leishmania infantum/efectos de los fármacos , Leishmania mexicana/efectos de los fármacos , Myristicaceae/química , Extractos Vegetales/farmacología , Anisoles/química , Anisoles/aislamiento & purificación , Anisoles/farmacología , Antiprotozoarios/química , Antiprotozoarios/toxicidad , Concentración 50 Inhibidora , Lignanos/química , Lignanos/aislamiento & purificación , Lignanos/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/parasitología , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidadRESUMEN
This study assessed the effects of essential oil of Foeniculum vulgare Mill. (fennel oil) and of trans-anethole, the main component of fennel oil, on extracellular Ca2+-induced store-operated Ca2+ entry (SOCE) into vascular endothelial (EA) cells and their mechanisms of action. Components of fennel oil were analyzed by gas chromatography-mass spectrometry. Cytosolic Ca2+ concentration ([Ca2+]c) in EA cells was determined using Fura-2 fluorescence. In the presence of extracellular Ca2+, fennel oil significantly increased [Ca2+]c in EA cells; this increase was significantly inhibited by the Ca2+ channel blockers La3+ and nifedipine. In contrast, fennel oil induced [Ca2+]c was significantly lower in Ca2+-free solution, suggesting that fennel oil increases [Ca2+]c mainly by enhancing Ca2+ influx into EA cells. [Ca2+]c mobilization by trans-anethole was similar to that of fennel oil. Moreover, SOCE was suppressed by fennel oil and trans-anethole. SOCE was also attenuated by lanthanum (La3+), a non-selective cation channel (NSC) blocker; 2-aminoethoxydiphenyl borane (2-APB), an inositol 1,4,5-triphosphate (IP3) receptor inhibitor and SOCE blocker; and U73122, an inhibitor of phospholipase C (PLC). Further, SOCE was more strongly inhibited by La3+ plus fennel oil or trans-anethole than by La3+ alone. These findings suggest that fennel oil and trans-anethole significantly inhibit SOCE-induced [Ca2+]c increase in vascular endothelial cells and that these reactions may be mediated by NSC, IP3-dependent Ca2+ mobilization, and PLC activation.
Asunto(s)
Calcio/metabolismo , Citosol/metabolismo , Células Endoteliales/metabolismo , Foeniculum , Extractos Vegetales/farmacología , Aceites de Plantas/farmacología , Derivados de Alilbenceno , Anisoles/aislamiento & purificación , Anisoles/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Citosol/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Humanos , Extractos Vegetales/aislamiento & purificación , Aceites de Plantas/aislamiento & purificaciónRESUMEN
The Department of Defense (DoD) is developing a new category of insensitive munitions (IMs) that are more resistant to detonation or promulgation from external stimuli than traditional munition formulations. The new explosive constituent compounds are 2,4-dinitroanisole (DNAN), nitroguanidine (NQ), and nitrotriazolone (NTO). The production and use of IM formulations may result in interaction of IM component compounds with soil. The chemical properties of these IM compounds present unique challenges for extraction from environmental matrices such as soil. A two-stage extraction procedure was developed and tested using several soil types amended with known concentrations of IM compounds. This procedure incorporates both an acidified phase and an organic phase to account for the chemical properties of the IM compounds. The method detection limits (MDLs) for all IM compounds in all soil types were <5 mg/kg and met non-regulatory risk-based Regional Screening Level (RSL) criteria for soil proposed by the U.S. Army Public Health Center. At defined environmentally relevant concentrations, the average recovery of each IM compound in each soil type was consistent and greater than 85%. The two-stage extraction method decreased the influence of soil composition on IM compound recovery. UV analysis of NTO established an isosbestic point based on varied pH at a detection wavelength of 341 nm. The two-stage soil extraction method is equally effective for traditional munition compounds, a potentially important point when examining soils exposed to both traditional and insensitive munitions.