RESUMO
Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.
Assuntos
Animais , Masculino , Camundongos , Ansiedade/tratamento farmacológico , Ansiolíticos/uso terapêutico , Óleos Voláteis/uso terapêutico , Citrus/química , Moduladores GABAérgicos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Ansiolíticos/isolamento & purificação , Aprendizagem em Labirinto/efeitos dos fármacos , Hipnóticos e Sedativos/isolamento & purificaçãoRESUMO
Studies using silver catfish (Rhamdia quelen) as experimental models are often applied to screen essential oils (EO) with GABAergic-mediated effects. However, the expression of GABAa receptors in the silver catfish brain remains unknown. Thus, we assessed whether silver catfish express GABAa receptor subunits associated with sedation/anesthetic process and/or neurological diseases. Additionally, we evaluated the brain expression of GABAa receptor subunits in fish sedated with Nectandra grandiflora EO and its isolated compounds, the fish anesthetic (+)-dehydrofukinone (DHF), and dehydrofukinone epoxide (DFX), eremophil-11-en-10-ol (ERM) and selin-11-en-4-α-ol (SEL), which have GABAa-mediated anxiolytic-like effects in mice. The expression of the subunits gabra1, gabra2, gabra3, gabrb1, gabrd and gabrg2 in the silver catfish brain were assessed after a 24h-sedation bath by real time PCR. Since qPCR data rarely describes mechanisms of action, which are usually found through interactions with receptors, we also performed an antagonist-driven experiment using flumazenil (FMZ). Real-time PCR detected the mRNA expression of all targeted genes in R. quelen brain. The expression of gabra1 was decreased in fish sedated with ERM; EO increased gabra2, gabra3, gabrb1 and gabrg2 expression; SEL increased gabrb1, gabrd and gabrg2 expression. EO and compounds DFX, SEL and ERM induced sustained sedation in fish and FMZ-bath prompted the recovery from ERM- and DFX-induced sedation. Our results suggest that the EO, SEL, ERM and DFX sedative effects involve interaction with the GABAergic system. Our findings support the use of the silver catfish as robust and reliable experimental model to evaluate the efficacy of drugs with putative GABAergic-mediated effects.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Proteínas de Peixes/metabolismo , GABAérgicos/farmacologia , Óleos Voláteis/farmacologia , Receptores de GABA-A/metabolismo , Animais , Peixes-Gato , GABAérgicos/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Lauraceae , Óleos Voláteis/isolamento & purificação , Folhas de Planta , RNA Mensageiro/metabolismoRESUMO
Galphimia glauca is a plant that is endemic to Mexico and has been commonly used since pre-Hispanic times to treat various illnesses, including central nervous system disorders and inflammation. The first studies investigating a natural population of G. glauca in Mexico showed that the plant has anxiolytic and sedative activities in mice and humans. The plant's bioactive compounds were isolated and identified, and they belong to a family of nor-secofriedelanes called galphimines. The integration of DNA barcoding and thin-layer chromatography analysis was performed to clarify whether the botanical classification of the populations in the study, which were collected in different regions of Mexico, as G. glauca was correct or if the populations consist of more than one species of the genus Galphimia. We employed six DNA barcodes (matK, rbcL, rpoC1, psbA-trnH, ITS1 and ITS2) that were analyzed individually and in combination and then compared each other, to indicate differences among the studied populations. In the phylogenetic analysis, ITS1 and ITS2 markers as well as the combination of all DNA regions were the most efficient for discriminating the population studied. The thin-layer chromatography analysis exhibited four principal chemical profiles, one of which corresponded to the populations that produced galphimines. DNA barcoding was consistent and enabled us to differentiate the populations that produce galphimines from those that do not. The results of this investigation suggest that the studied populations belong to at least four different species of the genus Galphimia. The phylogenetic analysis and the thin-layer chromatography chemical profiles were convenient tools for establishing a strong relationship between the genotype and phenotype of the studied populations and could be used for quality control purposes to prepare herbal medicines from plants of the genus Galphimia.
Assuntos
Galphimia/classificação , Plantas Medicinais/classificação , Animais , Ansiolíticos/isolamento & purificação , Sequência de Bases , Cromatografia em Camada Fina , Código de Barras de DNA Taxonômico , DNA de Plantas/genética , Galphimia/química , Galphimia/genética , Genes de Plantas , Humanos , Hipnóticos e Sedativos/isolamento & purificação , México , Camundongos , Filogenia , Plantas Medicinais/química , Plantas Medicinais/genética , Especificidade da EspécieRESUMO
ABSTRACT This study aimed to verify the sedative and anaesthetic effect of the essential oils of basil (Ocimum basilicum) (EOOB) and lemongrass (Cymbopogum flexuosus) (EOCF) in Nile tilapia juveniles. The fish were transferred to aquaria containing different concentrations of each essential oil: 10, 25, 50, 100, 200, 400 and 600 μL L-1. The time of sedation ranged from 7 to 31 seconds and the recommended concentration was 10 or 25 μL L-1 for both essential oils. The best times for anaesthesia and recovery were found for the concentrations of 400 μL L-1 for EOOB (135.2 and 199.1 seconds, respectively) and 600 μL L-1 for EOCF (327.1 and 374.8 seconds, respectively). In conclusion, we recommend the use of EOOB and EOCF for the sedation and anaesthesia of Nile tilapia at concentrations of 10-25 (for both), 400 and 600 μL L-1, respectively.
Assuntos
Animais , Óleos Voláteis , Ocimum basilicum/química , Ciclídeos , Cymbopogon/química , Hipnóticos e Sedativos/isolamento & purificação , Anestesia , Anestésicos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de MassasRESUMO
This study aimed to verify the sedative and anaesthetic effect of the essential oils of basil (Ocimum basilicum) (EOOB) and lemongrass (Cymbopogum flexuosus) (EOCF) in Nile tilapia juveniles. The fish were transferred to aquaria containing different concentrations of each essential oil: 10, 25, 50, 100, 200, 400 and 600 µL L-1. The time of sedation ranged from 7 to 31 seconds and the recommended concentration was 10 or 25 µL L-1 for both essential oils. The best times for anaesthesia and recovery were found for the concentrations of 400 µL L-1 for EOOB (135.2 and 199.1 seconds, respectively) and 600 µL L-1 for EOCF (327.1 and 374.8 seconds, respectively). In conclusion, we recommend the use of EOOB and EOCF for the sedation and anaesthesia of Nile tilapia at concentrations of 10-25 (for both), 400 and 600 µL L-1, respectively.
Assuntos
Anestesia , Anestésicos , Ciclídeos , Cymbopogon/química , Hipnóticos e Sedativos , Ocimum basilicum/química , Óleos Voláteis , Anestésicos/isolamento & purificação , Animais , Cromatografia Gasosa-Espectrometria de Massas , Hipnóticos e Sedativos/isolamento & purificaçãoRESUMO
OBJECTIVE: The present study describes the isolation of linalool from the essential oil of Lippia alba (Mill.) N. E. Brown, and its anesthetic effect in silver catfish (Rhamdia quelen) in comparison with essential oil. The potentiation of depressant effects of linalool with a benzodiazepine (BDZ) and the involvement of GABAergic system in its antagonism by flumazenil were also evaluated. STUDY DESIGN: Prospective experimental study. ANIMALS: Juvenile silver catfish unknown sex weighing mean 9.24 ± 2.83 g (n = 6 for each experimental group per experiment). METHODS: Column chromatography was used for the isolation of S-(+)-linalool. Fish (n = 6 for each concentration) were transferred to aquaria with linalool (30, 60, and 180 µL L(-1)) or EO of L. alba (50, 100, and 300 µL L(-1)) to determine the induction time for anesthesia. After induction, the animals were transferred to anesthetic-free aquaria to assess their recovery time. To observe the potentiation, fish were exposed to linalool (30, 60, and 180 µL L(-1)) in the presence or absence of BDZ (diazepam 150 µm). In another experiment, fish exposed to linalool (30 and 180 µL L(-1) or BDZ were transferred to an anesthetic-free aquaria containing flumazenil (5 µm) or water to assess recovery time. RESULTS: Linalool had a similar sedation profile to the essential oil at a proportional concentration in silver catfish. However, the anesthesia profile was different. Potentiation of linalool effect occurred only when tested at low concentration. Fish exposed to BDZ showed faster anesthesia recovery in water with flumazenil, but the same did not occur with linalool. CONCLUSIONS AND CLINICAL RELEVANCE: The use of linalool as a sedative and anesthetic for silver catfish was effective at 30 and 180 µL L(-1), respectively. The mechanism of action seems not to involve the benzodiazepine site of the GABAergic system.
Assuntos
Anestesia/veterinária , Peixes-Gato , Hipnóticos e Sedativos/farmacologia , Lippia/química , Monoterpenos/farmacologia , Monoterpenos Acíclicos , Anestesia/métodos , Anestésicos/isolamento & purificação , Anestésicos/farmacologia , Animais , Sistema Nervoso Central/efeitos dos fármacos , Diazepam/farmacologia , Flumazenil/farmacologia , Hipnóticos e Sedativos/isolamento & purificação , Monoterpenos/isolamento & purificação , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Agastache mexicana subspecies mexicana (Amm) and xolocotziana (Amx) are used in Mexican traditional medicine to relief cultural affiliation syndromes known as "susto" or "espanto", for "nervous" condition, and as a sleep aid. Despite its intensive use, neuropharmacological studies are scarce, and the chemical composition of the aqueous extracts has not been described. Aims of the study are: (1) To analyze the chemical composition of aqueous extracts from aerial parts of Amm and Amx. (2) To evaluate the anxiolytic-like, sedative, antidepressant-like effects. (3) Analyze the general toxic effects of different doses. MATERIALS AND METHODS: Anxiolytic-like and sedative effects were measured in the avoidance exploratory behavior, burying behavior and the hole-board tests. The antidepressant-like actions were studied in the forced swimming and tail suspension tests. Finally, general activity and motor coordination disturbances were evaluated in the open field, inverted screen and rota-rod tests. The acute toxicity of Amm and Amx was determined by calculating their LD50 (mean lethal dose). The chemical analyses were performed employing chromatographic, photometric and HPLC-ESI-MS techniques. RESULTS: Low doses of Amm and Amx (0.1σ1.0mg/kg) induced anxiolytic-like actions; while higher doses (over 10mg/kg) induced sedation and reduced the locomotor activity, exerting a general inhibition in the central nervous system (CNS). CONCLUSIONS: Results support the use of Amm and Amx in traditional medicine as tranquilizers and sleep inducers. Additionally, this paper contributes to the knowledge of the chemical composition of the aqueous extracts of these plants.
Assuntos
Agastache/química , Ansiolíticos/farmacologia , Hipnóticos e Sedativos/farmacologia , Extratos Vegetais/farmacologia , Animais , Ansiolíticos/isolamento & purificação , Ansiolíticos/toxicidade , Antidepressivos/isolamento & purificação , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/toxicidade , Dose Letal Mediana , Masculino , Medicina Tradicional/métodos , México , Camundongos , Atividade Motora/efeitos dos fármacos , Componentes Aéreos da Planta , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Testes de Toxicidade AgudaRESUMO
This study evaluated the sedative and anesthetic effects of the essential oils (EO) of Hyptis mutabilis (Rich.) Briq. and their isolated components on silver catfish (Rhamdia quelen). Quantitative chemical differences between the EOs obtained from leaves and inflorescences were verified, and a new chemotype rich in globulol was described. Although there were no significant differences in the time of induction for sedation and anesthesia between the EOs, only the leaf EO at 344 mg/L anesthetized all fish without side effects. Fractionation of the leaf EO was carried out by column chromatography. The isolated compounds [(+)-1-terpinen-4-ol and (-)-globulol] showed different activity from that detected for the leaf EO in proportional concentrations and similar sedation to a eugenol control at 10 mg/L. However, fish exposed to 1-terpinen-4-ol (3 and 10 mg/L) did not remain sedated for 30 min. Anesthesia was obtained with 83-190 mg/L globulol, but animals showed loss of mucus during induction and mortality at these concentrations. Synergism of the depressor effects was detected with the association of globulol and benzodiazepine (BDZ), compared with either drug alone. Fish exposed to BDZ or globulol+BDZ association showed faster recovery from anesthesia in water containing flumazenil, but the same did not occur with globulol. In conclusion, the use of globulol in aquaculture procedures should be considered only at sedative concentrations of 10 and 20 mg/L, and its mechanism of action seems not to involve the GABAA-BDZ system.
Assuntos
Anestésicos/farmacologia , Peixes-Gato , Hipnóticos e Sedativos/farmacologia , Hyptis/química , Óleos Voláteis/farmacologia , Análise de Variância , Anestésicos/isolamento & purificação , Animais , GABAérgicos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Hipnóticos e Sedativos/isolamento & purificação , Inflorescência/química , Mortalidade , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacocinética , Estatísticas não Paramétricas , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
This study evaluated the sedative and anesthetic effects of the essential oils (EO) of Hyptis mutabilis (Rich.) Briq. and their isolated components on silver catfish (Rhamdia quelen). Quantitative chemical differences between the EOs obtained from leaves and inflorescences were verified, and a new chemotype rich in globulol was described. Although there were no significant differences in the time of induction for sedation and anesthesia between the EOs, only the leaf EO at 344 mg/L anesthetized all fish without side effects. Fractionation of the leaf EO was carried out by column chromatography. The isolated compounds [(+)-1-terpinen-4-ol and (-)-globulol] showed different activity from that detected for the leaf EO in proportional concentrations and similar sedation to a eugenol control at 10 mg/L. However, fish exposed to 1-terpinen-4-ol (3 and 10 mg/L) did not remain sedated for 30 min. Anesthesia was obtained with 83-190 mg/L globulol, but animals showed loss of mucus during induction and mortality at these concentrations. Synergism of the depressor effects was detected with the association of globulol and benzodiazepine (BDZ), compared with either drug alone. Fish exposed to BDZ or globulol+BDZ association showed faster recovery from anesthesia in water containing flumazenil, but the same did not occur with globulol. In conclusion, the use of globulol in aquaculture procedures should be considered only at sedative concentrations of 10 and 20 mg/L, and its mechanism of action seems not to involve the GABAA-BDZ system.
Assuntos
Animais , Anestésicos/farmacologia , Peixes-Gato , Hipnóticos e Sedativos/farmacologia , Hyptis/química , Óleos Voláteis/farmacologia , Análise de Variância , Anestésicos/isolamento & purificação , GABAérgicos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Hipnóticos e Sedativos/isolamento & purificação , Inflorescência/química , Mortalidade , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Estatísticas não Paramétricas , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacocinética , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
CONTEXT: The genus Urtica has been known since ancient times. It has known to be useful for the treatment of different human ailments. OBJECTIVE: The present work evaluated the neuropharmacological effects of a hydroalcoholic extract of Urtica circularis (Hicken) Sorarú (Urticaceae). materials and method: The effect on central nervous system of U. circularis hydroalcoholic extract (from leaves and stems) administered by the intraperitoneal route in mice was evaluated by several tests: Pentobarbital- and midazolam-induced hypnosis, open field, hole board, elevated plus-maze and forced swimming. Phytochemical analysis was performed by high-performance liquid chromatography. RESULTS: A total of 300 mg/kg i.p. of the extract produced a significant prolongation of pentobarbital- (40 mg/kg i.p.; 60.1 min versus 25.4 min) and midazolam- (50 mg/kg i.v.; 53.4 min versus 25.1 min) induced sleeping time. The extract's administration caused a marked reduction of the head-dipping response (DE50: 373 mg/kg i.p.) in the hole-board test. Urtica circularis extract (DE50: 46 mg/kg i.p.) reduced the spontaneous locomotor activity in the open field test. Flumazenil and atropine significantly antagonized the extract's effect on the locomotor activity. No motor coordination disturbance was observed in the rota rod test at any doses. In the forced swimming test, the extract did not produce any change in the immobility time and it had no significant effects in elevated plus maze test. The phytochemical analysis revealed the presence of chlorogenic acid, vanillic acid, caffeic acid, vicenin-2, p-cumaric acid, ferulic acid, vitexin and isovitexin. CONCLUSION: This study revealed that U. circularis hydroalcoholic extract possesses sedative activity, facilitating GABAergic and cholinergic transmission.
Assuntos
Comportamento Animal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Etanol/química , Hipnóticos e Sedativos/farmacologia , Extratos Vegetais/farmacologia , Solventes/química , Urticaceae , Acetilcolina/metabolismo , Animais , Sistema Nervoso Central/metabolismo , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Injeções Intraperitoneais , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Caules de Planta , Plantas Medicinais , Sono/efeitos dos fármacos , Natação , Transmissão Sináptica/efeitos dos fármacos , Fatores de Tempo , Urticaceae/química , Ácido gama-Aminobutírico/metabolismoRESUMO
CONTEXT: Essential oils (EOs) have been reported to possess pharmacological properties, of which those related to the central nervous system have been especially attributed to mono- and sesquiterpenes. Baccharis uncinella DC. (Asteraceae) is used by the Laklaño Indians (Santa Catarina, Brazil) for sedative purposes. Interestingly, the species does not seem to be used medicinally elsewhere in Brazil. OBJECTIVE: This study was designed to compare the composition and sedative properties of B. uncinella EOs obtained closer (BU-SC) and farther (BU-PR) to the Laklaño Indian Reserve. MATERIALS AND METHODS: BU-SC and BU-PR obtained by hydrodistillation were analyzed by CG-MS. Mice treated with BU-SC and BU-PR (50 and 100 mg/kg) were evaluated regarding pentobarbital-induced sleeping time, body temperature, and locomotion. RESULTS: BU-SC presents a higher monoterpene/sesquitherpene ratio (0.31); α-pinene (6.42%), limonene (7.21%), caryophyllene (26.13%), spathulenol (13.39%) and caryophyllene oxide (13.26%) were identified as major components. BU-PR presents a low monoterpene/sesquitepene ratio (0.004); spathulenol (32.93%), caryophyllene oxide (27.78%), viridiflorol (5.29%) and α-cadinol (2.42%) were identified as the main components. Both samples significantly (p < 0.05, ANOVA) decreased locomotion and body temperature, as well as increased sleeping time. The hypnotic activity was sensitive to the differences in monoterpene composition. CONCLUSIONS: In comparison with a sample collected in Paraná State, B. uncinella EO collected closer to the Laklaño Indians possess a composition that better justifies the claimed sedative properties. The study confirms the value of traditional information to guide bioactivity assessment in medicinal plants, and gives notice to the ecological factors that can interfere with the conclusions of such assessments.
Assuntos
Baccharis/química , Hipnóticos e Sedativos/farmacologia , Óleos Voláteis/farmacologia , Sono/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Brasil , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/isolamento & purificação , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óleos Voláteis/administração & dosagem , Óleos Voláteis/isolamento & purificação , Fatores de TempoRESUMO
Species of genus Ocimum (Lamiaceae) are economically important due to their essential oils and utilization as medicine for many disorders, including the central nervous system. A previous study showed seasonal variations in chemical profile and in central nervous system activities of essential oil from Ocimum gratissimum L. The preparation obtained in spring was able to protect the animals against tonic episodes induced by electroshock while those obtained in other seasons were effective in increasing barbiturate-induced sleeping time. The chemical analysis of essential oils showed eugenol and 1,8-cineole as principal compounds and trans-caryophyllene as a sesquiterpene in higher proportion. In the present study these three compounds were evaluated, separately or mixed in the same proportion detected in spring, in the open-field and rota-rod tests, against convulsions induced by pentylenetetrazole (PTZ; 60 mg/kg, subcutaneously, s.c.) or maximal electroshock (MES; 50 mA, 0.11 s) and in sodium pentobarbital (45 mg/kg, intraperitoneally, i.p.)-induced sleeping time. The compounds, isolated or in association, did not show efficaciousness in altering convulsive episodes, and only when in association were able to increase sleeping time duration. The absence of similar essential oil activity in the isolated compounds contributes to the idea that the major compounds are not always responsible for a biological effect observed in medicinal plant preparations. This view reinforces the concept of a multitargeted approach as a therapeutic strategy, contributing to an integrated understanding of the phenomena related to experimental activity of a complex herbal mixture.
Assuntos
Anticonvulsivantes/farmacologia , Hipnóticos e Sedativos/farmacologia , Ocimum/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Animais , Anticonvulsivantes/isolamento & purificação , Sinergismo Farmacológico , Hipnóticos e Sedativos/isolamento & purificação , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Ocimum/fisiologia , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/isolamento & purificaçãoRESUMO
The flavone glycosides, named scutellarein-7-O-beta-D-apiofuranoside and apigenin-7-O-beta-D-apiofuranosyl-(1-->2)-beta-D-apiofuranoside, and the flavone celtidifoline (5,6,4',5'-tetrahydroxy-7,3'-dimethoxyflavone), along with other 11 known compounds, were isolated from leaves of the ethyl acetate extract of Lantana trifolia L. using step gradient High Speed Countercurrent Chromatography (HSCCC) and High Performance Liquid Chromatography (HPLC), respectively. Their structures were elucidated by spectroscopic methods, including 2D NMR and mass spectrometry (ESI-MS) techniques. The ethanolic and ethyl acetate extracts produced an intense sedative effect in mice, one hour after oral administration of 1 mg/kg. This effect was neither due to a benzodiazepine-like effect of the three flavone derivatives neither of the phenylpropanoids, betonyoside F and verbascoside, that were tested for their affinity for the [3H] flunitrazepam binding sites.
Assuntos
Flavonas/farmacologia , Hipnóticos e Sedativos/farmacologia , Lantana/química , Extratos Vegetais/farmacologia , Propanóis/farmacologia , Animais , Flavonas/química , Flavonas/isolamento & purificação , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Masculino , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta , Propanóis/química , Propanóis/isolamento & purificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ternstroemia pringlei represents one of the most widely employed and commercially exploited medicinal plant in Mexico, used popularly as a tranquilizer and for the treatment of insomnia. AIM OF THE STUDY: To investigate the sedative constituents of the plant through a bio-guided fractionation of extracts derived from calyx and fruits. MATERIALS AND METHODS: Crude extracts with different polarities (CHCl(3), AcOEt, MeOH, aqueous) were prepared and subjected to chromatographic fractionation, leading to the isolation of the sedative compound (1) from the MeOH crude extract. The identity of 1 was unequivocally established by means of 1D and 2D NMR spectroscopic analysis. The sleeping time induced by sodium pentobarbital and the elevated plus-maze models were performed on mice to determine the sedative and anxiolytic activities, respectively. Bioactivity was also investigated though in vitro GABA release experiments using mice brain slices. RESULTS: The sedative compound was established as jacaranone (1), and its effect was clearly demonstrated through a dose-dependent response analysis (ED(50) = 25 mg/kg mouse weight). When tested in the elevated plus-maze model, none of the extracts from Ternstroemia pringlei displayed anxiolytic activity. GABA release experiments showed that the MeOH and aqueous crude extracts released this neurotransmitter at a ratio of 217 and 179 pmol/g protein, respectively, evidencing the presence of other bioactive constituents in the extracts apart of 1, whose activity was absent in this model. CONCLUSIONS: Although 1 has been isolated and identified in a number of plant species, this is the first time that its sedative effect has been demonstrated. No previous record exists of other sedative compounds having been isolated from Ternstroemia pringlei.
Assuntos
Benzoquinonas/isolamento & purificação , Benzoquinonas/uso terapêutico , Brassicaceae , Flores , Hipnóticos e Sedativos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Theaceae , Árvores , Animais , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Benzoquinonas/farmacologia , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Masculino , México , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/farmacologiaRESUMO
Pharmacological assay guided purification of an ethanol extract of Tilia petiolaris DC. inflorescences resulted in the isolation and identification of isoquercitrin (ISO), quercetin 3-O-glucoside-7-O-rhamnoside (QUE) and kaempferol 3-O-glucoside-7-O-rhamnoside (KAE). The behavioral actions of these glycosylated flavonoids were examined in the hole board, locomotor activity and thiopental-induced loss of righting reflex tests in mice. QUE (10 and 30 mg/kg) and KAE (30 mg/kg), intraperitoneally (i.p.) administered to mice, reduced all the parameters measured in the hole board test, but ISO (30 mg/kg) only reduced the number of rearings. Meanwhile QUE at 30 mg/kg i.p. also decreased the ambulatory locomotor activity and increased the sodium thiopental-induced time of loss of the righting reflex suggesting a clear depressant action. The above results demonstrate the occurrence of neuroactive flavonoid glycosides in Tilia.
Assuntos
Comportamento Animal/efeitos dos fármacos , Glucosídeos/farmacologia , Hipnóticos e Sedativos/farmacologia , Quempferóis/farmacologia , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Quercetina/análogos & derivados , Tilia/química , Animais , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glucosídeos/isolamento & purificação , Glicosilação , Hipnóticos e Sedativos/isolamento & purificação , Inflorescência , Quempferóis/isolamento & purificação , Masculino , Camundongos , Extratos Vegetais/química , Quercetina/isolamento & purificação , Quercetina/farmacologiaRESUMO
An in vitro micropropagation protocol is described for Galphimia glauca Cav. (Malpighighiaceae). Multiple shoots were formed in vitro from axillary bud explants inoculated on MS medium supplemented with indole-3-acetic acid (IAA) and kinetin (KN) combinations. A maximum of 20 shoots was obtained from a single bud in a 60-day culture period. In vitro-grown shoots were successfully rooted and transferred to field conditions (90 % survival). The sedative triterpenoid galphimine-B (1) content of micropropagated plants transferred to field conditions was similar to that of wild plants. Our results suggest that the in vitro propagation protocol described here will have positive effects on conservation of natural resources as well as on adequate techniques for multiplication of an important Mexican medicinal plant.
Assuntos
Galphimia/química , Galphimia/crescimento & desenvolvimento , Hipnóticos e Sedativos/análise , Triterpenos/análise , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Ácidos Indolacéticos/farmacologia , Cinetina/farmacologia , Estrutura Molecular , Farmacognosia/métodos , Extratos Vegetais/química , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Preparative-scale recycling HPLC was used for the complete resolution of a complex mixture of nor-secofriedelanes into five major peaks (I-V) from the sedative methanolic extracts prepared from the aerial parts of Galphimia glauca. Argentation chromatography was used to show peaks I, II, IV, and V to be mixtures of isomers around the E-ring double bond, represented by the endocyclic C-20, C-21 double-bond isomers, galphimines A (3), B (1), D (4), and E (2), and the C-20, C-29 exocyclic forms, galphimines F-I (5-8). Galphimine C (9), isolated from peak III, corresponded to the C-19, C-20 double-bond isomer of the previously known major sedative constituent galphimine B. The characterization of all the new triterpenes (3-9) was performed primarily by high-field NMR spectroscopy. Comparison between experimental and calculated (1)H-(1)H vicinal coupling constants and the analysis of molecular mechanics structures revealed that the ring B of these compounds exists in a boatlike conformation. The absolute configuration for the stereogenic carbinol center at C-4 was established by the application of the Mosher ester derivatization technique carried out in NMR tubes.
Assuntos
Galphimia/química , Hipnóticos e Sedativos/isolamento & purificação , Plantas Medicinais/química , Triterpenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacologia , México , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Citrus aurantium L. is commonly used as an alternative treatment for insomnia, anxiety and epilepsy. Essential oil from peel (EOP) and hydroethanolic (70% w/v) extract (HE) from leaves were obtained. Hexanic (HF), dichloromethanic (DF) and final aqueous (AF) fractions were obtained from HE by successive partitions. Swiss male mice (35-45 g) were treated orally with 0.5 or 1.0 g/kg of these preparations 30 min before the experiments for the evaluation of the sedative/hypnotic activity (sleeping time induced by sodium pentobarbital - SPB: 40 mg/kg, i.p.), anxiolytic activity (elevated plus maze--EPM) and anticonvulsant activity (induced by pentylenetetrazole--PTZ: 85 mg/kg, sc or by maximal electroshock--MES: 50 mA, 0.11 s, corneal). The results showed that EOP (0.5 g/kg) increased the latency period of tonic seizures in both convulsing experimental models. This effect was not dose-dependent. Treatment with 1.0 g/kg increased the sleeping time induced by barbiturates and the time spent in the open arms of the EPM. Specific tests indicated that the preparation, in both doses used, did not promote deficits in general activity or motor coordination. HF and DF fractions (1.0 g/kg) did not interfere in the epileptic seizures, but were able to enhance the sleeping time induced by barbiturates. The results obtained with EOP in the anxiety model, and with EOP, HF and DF in the sedation model, are in accord with the ethnopharmacological use of Citrus aurantium L., which could be useful in primary medical care, after toxicological investigation.
Assuntos
Ansiolíticos/uso terapêutico , Citrus , Hipnóticos e Sedativos/uso terapêutico , Óleos Voláteis/uso terapêutico , Animais , Ansiolíticos/isolamento & purificação , Ansiolíticos/farmacologia , Frutas , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Pentobarbital/farmacologia , Pentobarbital/uso terapêutico , Fitoterapia/métodos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Convulsões/tratamento farmacológico , Sono/efeitos dos fármacos , Sono/fisiologiaRESUMO
Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine as a sedative in the treatment of mental disorders. Sedative properties of a methanolic extract of the aerial parts of this plant have been established in animal trials and an active compound, named galphimine B, has already been isolated. This compound was submitted to neuropharmacological testing, where it was shown that galphimine B had no significant effect as an anticonvulsant, while it exhibited a strong depressant activity on the nervous system.
Assuntos
Anticonvulsivantes/farmacologia , Hipnóticos e Sedativos/farmacologia , Plantas Medicinais/química , Triterpenos/farmacologia , Animais , Anticonvulsivantes/isolamento & purificação , Feminino , Cobaias , Hipnóticos e Sedativos/isolamento & purificação , Masculino , Camundongos , Estrutura Molecular , Triterpenos/isolamento & purificaçãoRESUMO
"Paico," Chenopodium ambrosioides L., is a traditional Peruvian medicine which is considered to be nervine, antirheumatic, anthelmintic, etc. An attempt was made to isolate the component having sedative and/or analgesic properties from "Paico" and "Aritasou" (the Japanese name for C. ambrosioides). Ascaridole was identified as the active principle in both materials.