RESUMO
BACKGROUND: Chalcones and dihydrochalcones present potent inhibition of acetylcholinesterase, currently considered the most efficient approach for symptomatic treatment of Alzheimer's disease. OBJECTIVE: The present study aimed to explore the potential benefits of 2',6'-dihydroxy-4'-methoxy dihydrochalcone on the cognitive deficits of animals submitted to the streptozotocin-induced Alzheimer's model, as well as evaluating the possible mechanisms of action. METHODS: Learning and memory functions of different groups of animals were submitted to the streptozotocin-induced Alzheimer's model (STZ 2.5 mg/mL, i.c.v.) and subsequently treated with 2',6'-dihydroxy-4'-methoxy dihydrochalcone (DHMDC) administered at doses of 5, 15, and 30 mg/kg (p.o.), respectively. Rivastigmine (0,6 mg/kg, i.p.) and vehicle were evaluated in aversive memory test (inhibitory avoidance test) and spatial memory test (object recognition test). Molecular docking simulations were performed to predict the binding mode of DHMDC at the peripheral site of AChE, to analyze noncovalent enzyme-ligand interactions. DFT calculations were carried out to study well-known acetylcholinesterase inhibitors and DHMDC. RESULTS: DHMDC markedly increased the learning and memory of mice. STZ caused a significant decline of spatial and aversive memories in mice, attenuated by DHMDC (15 and 30 mg/kg). Furthermore, STZ conspicuously increased lipid peroxidation and compromised the antioxidant levels in mice brains. DHMDC pretreatment significantly increased GSH activity and other oxidative stress markers and decreased TBARS level in the brain of STZ administered mice. AChE activity was significantly decreased by DHMDC in the brain of mice. CONCLUSION: The results together point out that DHMDC may be a useful drug in the management of dementia.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Chalconas/farmacologia , Inibidores da Colinesterase/farmacologia , Transtornos Cognitivos/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/induzido quimicamente , Animais , Chalconas/química , Inibidores da Colinesterase/química , Transtornos Cognitivos/induzido quimicamente , Teoria da Densidade Funcional , Masculino , Camundongos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/química , Estreptozocina , Relação Estrutura-AtividadeRESUMO
Ketamine has been reported to exert a prophylactic effect against stress-induced depressive-like behavior by modulating the guanosine-based purinergic system. However, the molecular pathways underlying its prophylactic effect and whether guanosine also elicits a similar effect remain to be determined. Here, we investigated the prophylactic effect of ketamine and guanosine against corticosterone (CORT - 20â¯mg/kg, p.o.)-induced depressive-like behavior in mice. Furthermore, we characterized if the prophylactic response may be associated with mTORC1-driven signaling in the hippocampus and prefrontal cortex. A single administration of ketamine (5â¯mg/kg, i.p.), but not guanosine (1 or 5â¯mg/kg, p.o.), given 1â¯week before the pharmacological stress prevented CORT-induced depressive-like behavior in the tail suspension test (TST) and splash test (SPT). Fluoxetine treatment for 3â¯weeks did not prevent CORT-induced behavioral effects. A single administration of subthreshold doses of ketamine (1â¯mg/kg, i.p.) plus guanosine (5â¯mg/kg, p.o.) partially prevented the CORT-induced depressive-like behavior in the SPT. Additionally, CORT reduced Akt (Ser473) and GSK-3ß (Ser9) phosphorylation and PSD-95, GluA1, and synapsin immunocontent in the hippocampus, but not in the prefrontal cortex. No alterations on mTORC1/p70S6K immunocontent were found in both regions in any experimental group. CORT-induced reductions on PSD-95, GluA1, and synapsin immunocontent were prevented only by ketamine treatment. Collectively, these findings suggest that ketamine, but not guanosine, exerts a prophylactic effect against depressive-like behavior, an effect associated with the stimulation of long-lasting pro-synaptogenic signaling in the hippocampus.
Assuntos
Corticosterona/toxicidade , Depressão/prevenção & controle , Guanosina/administração & dosagem , Ketamina/administração & dosagem , Profilaxia Pré-Exposição/métodos , Sinapses/fisiologia , Animais , Antidepressivos/administração & dosagem , Depressão/induzido quimicamente , Depressão/psicologia , Elevação dos Membros Posteriores/efeitos adversos , Elevação dos Membros Posteriores/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sinapses/efeitos dos fármacosRESUMO
BACKGROUND: People living in settlement projects represent an emergent rural population in Brazil. Data on their health is scarce and there are no data on viral hepatitis in this population. This study investigated the epidemiology of viral hepatitis A-E in residents of settlement projects in central Brazil. METHODS: During 2011 and 2012, 923 people living in rural settlements in central Brazil were interviewed and tested to estimate the prevalence of exposure to viral hepatitis A-E, to identify the circulating hepatitis B virus (HBV)/hepatitis C virus (HCV) genotypes and risk factors for HBV exposure and to evaluate adherence to the hepatitis B vaccination series. RESULTS: Overall, 85.9, 3.9, 0.4 and 17.3% of individuals showed evidence of exposure to hepatitis A virus (HAV), hepatitis E virus, HCV and HBV, respectively. Among HBV-DNA positive samples (n=8), subgenotypes A1 (n=3) and A2 (n=1) and genotype D/subgenotype D3 (n=4) were identified. Hepatitis D virus superinfection was detected in 0/16 HBsAg-positive participants. A total of 229 individuals showed serological evidence of HBV vaccination. In total, 442 settlers were eligible for vaccination, but only 150 individuals completed the vaccine series. All anti-HCV-positive samples (n=4) were also HCV-RNA positive and identified as subtype 1a. CONCLUSIONS: The intermediate endemicity of HAV, the higher prevalence of HBV exposure compared with urban areas and the low compliance with HBV vaccination requires preventive measures focused on rural populations, emphasizing the need for HAV and HBV vaccination.
Assuntos
Hepatite A , Hepatite B , Hepatite C , Hepatite D , Hepatite E , Vacinação/estatística & dados numéricos , Brasil/epidemiologia , Genótipo , Hepacivirus/genética , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B/genética , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepatite D/epidemiologia , Hepatite D/prevenção & controle , Vírus Delta da Hepatite/genética , Hepatite E/epidemiologia , Hepatite E/prevenção & controle , Vírus da Hepatite E/genética , Humanos , Prevalência , Fatores de Risco , População RuralAssuntos
Obesidade Infantil , Treinamento Resistido , Índice de Massa Corporal , Criança , Exercício Físico , HumanosRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death, characteristic of the effect of time on biochemical neuronal function. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research, since the standard drugs have many side effects. Taraxerol (TRX) is a triterpene that has been isolated from several plant species, and its various pharmacological properties have already been identified, such the acetylcholinesterase (AChE) inhibition activity in vitro. There is a lack of information in literature that confirms the effect of TRX in an animal AD-like model. Seeking to fill this gap in the literature, in the present work we assessed the effect of TRX on AChE activity in the animals' encephalon and hippocampus. We also investigated the effect of TRX (1.77⯵M/side, 0.5⯵L) isolated from leaves of Eugenia umbelliflora Berg. on aversive memory impairments induced by scopolamine (2⯵g/side, 0.5⯵L) infused into rat hippocampus, and the effect of TRX (0.89 and 1.77⯵M/side, 0.5⯵L) on aversive memory impairments induced by streptozotocin (STZ) (2.5â¯mg/mL, 2.0⯵L) infused i.c.v. into mice, using the step-down inhibitory avoidance task. We found that TRX significantly inhibited AChE activity in the animal's hippocampus. Furthermore, TRX significantly improved scopolamine and STZ-induced memory impairment. Taking together, these results confirms its AChE activity inhibition in animals and indicate that TRX has anti-amnesic activity that may hold significant therapeutic value in alleviating certain memory impairments observed in AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Memória/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Escopolamina/efeitos adversos , Estreptozocina/efeitos adversos , Acetilcolinesterase/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Ratos , Ratos WistarRESUMO
The aim of this study was to develop nanoemulsion containing soft extract of stem bark of Rapanea ferruginea to improve the topical delivery and anti-inflammatory activity. The extract of R. ferruginea stem bark was incorporated into the oily phase of the nanoemulsion by the method of phase inversion at low energy. The developed nanoemulsion had an average droplet size of 47.88±8.20 nm and a polydispersibility index of 0.228. Uniformity of size, spherical shape of droplet, and absence of clusters were confirmed by transmission electronic microscopy. The zeta potential was -34.7±1.15 mV. The nanoemulsion showed a moderate degree of skin irritation in the agarose overlay assay in vitro. The content of the extract markers, myrsinoic acids A and B, was 54.10±0.08 and 53.03 µg/g in the formulation, respectively. The formulation demonstrated pseudoplastic and thixotropic rheological behavior. In vitro release of chemical markers was controlled by diffusion mechanism. An extract-loaded nanoemulsion showed a topical anti-inflammatory activity in a croton oil-induced edema ear model, with a decrease in tumor necrosis factor release and myeloperoxidase activity. The nanoemulsion was 160% more efficient than the conventional cream containing 0.13% of the extract. The nanoemulsion showed suitable properties as a carrier for topical use of R. ferruginea extract and the approach for improving the topical anti-inflammatory activity.
RESUMO
Abstract The essential oil of Chenopodium ambrosioides L., Amaranthaceae, was obtained by steam distillation in a Clevenger apparatus and characterization was performed using chromatographic and spectroscopic assays (GC-FID, GC/MS, 1H NMR). Two major compounds were identified: p-cymene (42.32%) and ascaridole (49.77%). The ethanolic extract and hydrolate were fractionated by liquid–liquid partitioning and the compounds were characterized by GC/MS. The essential oil, ethanol extract and fractions by partitioning with dicloromethane, ethyl acetate and butanol were tested in tumor cell lines (K562, NALM6, B15, and RAJI). Significant cytotoxic activity was found for essential oil (IC50 = 1.0 µg/ml) for RAJI cells and fraction dicloromethane (IC50 = 34.0 µg/ml) and ethanol extract (IC50 = 47.0 µg/ml) for K562 cells. The activity of the essential oil of C. ambrosioides is probably related to the large amount of ascaridol, since the other major compound, p-cymene, is recognized as a potent anti-inflammatory and has low cytotoxic activity.
RESUMO
Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity.
Assuntos
Proliferação de Células , Hipertensão Portal/metabolismo , Cirrose Hepática/metabolismo , Osteopontina/metabolismo , Esquistossomose mansoni/metabolismo , Adolescente , Adulto , Animais , Antígenos de Helmintos/farmacologia , Ductos Biliares/citologia , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/metabolismo , Linhagem Celular , Células Cultivadas , Feminino , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Interações Hospedeiro-Parasita , Humanos , Hipertensão Portal/genética , Hipertensão Portal/parasitologia , Imuno-Histoquímica , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/parasitologia , Masculino , Camundongos , Pessoa de Meia-Idade , Osteopontina/sangue , Osteopontina/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Schistosoma/fisiologia , Esquistossomose mansoni/genética , Esquistossomose mansoni/parasitologia , Adulto JovemRESUMO
OBJECTIVES: Litchi chinensis has been traditionally used in folk medicine to treat several ailments. In this study, we investigated the chemical composition, antioxidant and antinociceptive activity of L. chinensis leaves. METHODS: The antioxidant capacity of the extract, fraction and compounds was evaluated using the 1,1-diphenyl-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, and the liposome model with peroxyl radicals generated by 2,2'-azobis (2-amidinopropane) dihydrochloride radical. The pharmacological models of acute nociception used in mice were: writhing test with acetic acid (AA), hotplate (HP), glutamate (GLU), capsaicin (CP) and formalin (FM) tests. KEY FINDINGS: The main compounds isolated were procyanidin A2 (PA2), procyanidin B2 (PB2) and (-)-epicatechin. The biochemical features of the crude extracts and their ethyl acetate fraction (EtOAcFR) presented high antioxidant activity, and the antioxidant activity of PA2 and PB2 was remarkably high, with DPPH and ABTS. The crude methanol extract (MeOHEXTR), EtOAcFR and PB2 were effective in reducing nociception in FM and HP models. MeOHEXTR and EtOAcFR treatments also reduced pain induced by GLU and AA. In the CP model, only EtOAcFR and PB2 were effective. CONCLUSIONS: The results demonstrate the antinociceptive and antioxidant of MeOHEXTR, EtOAcFR and PB2.
Assuntos
Analgésicos/farmacologia , Antioxidantes/farmacologia , Litchi/química , Extratos Vegetais/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/uso terapêutico , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Benzotiazóis/química , Compostos de Bifenilo/química , Peroxidação de Lipídeos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Dor/tratamento farmacológico , Dor/metabolismo , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Ácidos Sulfônicos/químicaRESUMO
Ipomoea pes-caprae (L.) R. Br., Convolvulaceae, is a medicinal plant that grows abundantly as a pan-tropical stand plant. The 3² (two factors and three levels) factorial design, was applied to determine the best time and drug/solvent proportion to maximize the flavonoid content in the hydroethanolic extract by maceration process. The antinociceptive and anti-inflammatory effects were studied at 5-20 mg/kg, i.p., using the writhing test and carrageenan-induced pleurisy models in mice. The optimized extract was able to inhibit more than 50% of abdominal writhing at 20 mg/kg, with 55.88%±2.4 of maximum inhibition. Indomethacin, used as positive control, inhibited 64.86% at 10 mg/kg. In the pleurisy model, the extract produced dose-dependent inhibition of the first phase of inflammation (4 h) in the pleural cavity induced by injection of carrageenan (1%) in mice. It inhibited 50%±0.82 (p<0.01) of exudation induced by carrageenan, and 60.88%±0.14 (p<0.01) of leukocyte migration to the pleural cavity. In conclusion, the results validate the technological conditions of the maceration process to produce an optimized bioactive herb extract for the development of analgesic and anti-inflammatory phytopharmaceuticals using 70 ºGL ethanol, a plant to solvent ratio of 12.5% (w/v), and ten days of maceration.
RESUMO
In this paper, we describe the antinociceptive activity, molecular modeling and in silico ADMET screening of a series of sulphonyl-hydrazone and sulphonamide imidobenzene derivatives. Among these compounds, the sulphonyl-hydrazones 9 and 11 showed the most potent analgesic activity (ID(50) = 5.1 and 6.8 µmol/kg, respectively). Interestingly, all derivatives evaluated in this study have a better analgesic profile than the control drugs, acetyl salicylic acid and acetaminophen. Derivative 9 was the most promising compound; with a level of activity that was 24 times higher than the control drugs. Our SAR study showed a relationship among the distribution of the frontier orbital HOMO coefficients, HOMO-LUMO energy gap of these molecules and their reactivity. The best analgesic compounds (including 6, 9, 10, 11 and 12) fulfilled the Lipinski "rule-of-five", which is theoretically important for good drug absorption and permeation.
Assuntos
Analgésicos/farmacologia , Desenho de Fármacos , Hidrazonas/farmacologia , Imidas/farmacologia , Sulfonamidas/farmacologia , Analgésicos/síntese química , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Modelos Animais de Doenças , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/uso terapêutico , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Imidas/síntese química , Imidas/química , Imidas/uso terapêutico , Camundongos , Modelos Moleculares , Estrutura Molecular , Dor/tratamento farmacológico , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/uso terapêuticoRESUMO
This study investigated the antinociceptive effect of Aleurites moluccana dried extract (DE; 125 to 500 mg/kg, p.o.) and the isolated flavonoid 2â³-O-rhamnosylswertisin (5 to 50.6 µmol/kg, p.o.) using different models of long-lasting inflammatory and neuropathic pain in mice. Attempts were made to analyse the mechanisms through which A. moluccana exerted its effects. A. moluccana DE inhibited complete Freund's adjuvant (CFA)-induced mechanical nociception. It was also evidenced by a reduction of sensitization in the contralateral hindpaw. The extract reversed the mechanical hypersensitivity of partial ligation of sciatic nerve (PLSN)-treated animals, similar to gabapentin. In PLSN model, the opioid, dopaminergic and oxidonitrergic pathways were involved in the A. moluccana DE antinociceptive effects. A single dose of 2â³-O-rhamnosylswertisin inhibited the carrageenan- and CFA-induced mechanical nociception. Furthermore, the compound caused expressive antinociception in PLSN-mice, with inhibition value greater than obtained with gabapentin. Oral treatment with the extract or the isolated compound attenuated the neutrophil migration and IL-1ß levels following carrageenan injection. Of note, A. moluccana DE did not interfere with thermal sensitivity in healthy mice. The absence of side effects, including interference in locomotor activity, motor performance in animals treated with the extract, showed excellent potential for the therapeutic use of this medicinal plant in treating persistent pain in humans.
Assuntos
Aleurites/química , Analgésicos/farmacologia , Flavonas/farmacologia , Dor/tratamento farmacológico , Ramnose/análogos & derivados , Analgésicos/uso terapêutico , Animais , Feminino , Flavonas/uso terapêutico , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Ramnose/farmacologia , Ramnose/uso terapêuticoRESUMO
We have recently shown that the ethanol extract of the leaves of Hedyosmum brasiliense exhibits an antidepressant-like effect in the tail suspension and forced swimming tests in mice. The present study investigates the mechanisms involved in the antidepressant-like effect of H. brasiliense extract, together with the antidepressant potential of podoandin, an isolated sesquiterpenoid. H. brasiliense (50mg/kg, i.p.) and podoandin (10mg/kg, i.p.) decreased the immobility time in the forced swimming test, without any accompanying changes in ambulation in the open-field test. The anti-immobility effect of the H. brasiliense extract was prevented by pre-treating the mice with ondansetron, NAN 190, pindolol, prazosin, yohimbine, haloperidol, SCH23390, and sulpiride. On the other hand, pre-treating the mice with: p-chlorophenylalanine (4 consecutive days), ketanserin, naloxone, naltrindole, bicuculline, phaclofen, or l-arginine did not block the antidepressant-like effect of H. brasiliense. In addition, pre-treatment of the animals with methylene blue, NG-nitro-l-arginine or 7-nitroindazole, at subeffective doses, did not cause a synergistic effect with H. brasiliense extract at an effective dose in the forced swimming test. The anti-immobility effect of podoandin was also prevented by pre-treating the mice with NAN-190, ondansetron, prazosin, yohimbine, sulpiride and haloperidol. The results indicate that the antidepressant-like effect of H. brasiliense (and podoandin) is dependent on the serotonergic, noradrenergic and dopaminergic systems, but not on the GABAergic, opioid and oxidonitrergic systems.
Assuntos
4-Butirolactona/análogos & derivados , Antidepressivos/farmacologia , Cicloeptanos/farmacologia , Gleiquênias/química , Lactonas/farmacologia , Neurotransmissores/metabolismo , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Analgésicos Opioides/metabolismo , Animais , Antidepressivos/isolamento & purificação , Arginina/metabolismo , GMP Cíclico/metabolismo , Cicloeptanos/isolamento & purificação , Dopamina/metabolismo , Interações Medicamentosas , Epinefrina/metabolismo , Fluoxetina/farmacologia , Lactonas/isolamento & purificação , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Extratos Vegetais/isolamento & purificação , Serotonina/metabolismo , Sesquiterpenos/isolamento & purificação , NataçãoRESUMO
Seeking to develop a new analgesic phytomedicine, a spray-dried extract (SDE) of Aleurites moluccana (L.) Willd. leaves was developed in scale up (5 kg). The SDE was standardized at 3% w/w in relation to the flavonoid 2''-O-rhamnosylswertisin. The SDE batches were evaluated in relation to their physical, physiochemical, and pharmacological characteristics. The results demonstrated the reproducibility of the scale up SDE process which, when dosed orally, reduced carrageenan-induced mechanical hypernociception, with an ID(50)% of 443 mg/kg. Similar results were obtained with animals injected with complete Freund's adjuvant (CFA), in which SDE caused inhibition of 48 ± 4%. SDE was effective in preventing prostaglandin E2 (PGE2)-induced mechanical hypernociception (inhibition of 26 ± 10% and 33 ± 3%, at 250 and 500 mg/kg, respectively). Swertisin and 2''-O-rhamnosylswertisin isolated from the own extract were effective in inhibiting the hypernociceptive response induced by carrageenan (70 ± 2% and 50 ± 5%, resp.). Furthermore, 2''-O-rhamnosylswertisin was capable of significantly inhibiting the mechanical sensitization induced by CFA or PGE2, with inhibitions of 25 ± 3% and 94 ± 6%, respectively. These results suggest that the effects of SDE are related, at least in part, to the presence of these flavonoids.
RESUMO
The aim of this study was to carry out pharmacological screening in order to evaluate the potential effects of lyophilized fruits of different cultivars of Vaccinium ashei Reade (Family Ericaceae) berries, commonly known as rabbiteye blueberries, on nociception. This was achieved using the formalin, hot plate, tail-flick, and writhing tests in mice. During this experiment the mice consumed approximately 3.2-6.4 mg/kg/day (p.o.) of the anthocyanins. The extract was administered for 21 days or 60 minutes before test. Morphine and diclofenac (10 mg/kg, p.o.) as the standard drug (positive control) and water (via oral gavage) as the negative control were administered before all tests. The blueberry extract produced a significant decrease in constrictions induced by acetic acid and caused graded inhibition of the second phase of formalin-induced pain. Moreover, in both the hot plate and tail-flick tests, it significantly increased the threshold. These data suggest that the extract from V. ashei produced antinociceptive effects, as demonstrated in the experimental models of nociception in mice. Additional experiments are necessary in order to clarify the true target for the antinociceptive effects of rabbiteye blueberry extract.
Assuntos
Analgésicos/uso terapêutico , Antocianinas/uso terapêutico , Mirtilos Azuis (Planta)/química , Dor/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Ácido Acético , Analgésicos/farmacologia , Animais , Antocianinas/farmacologia , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Modelos Animais de Doenças , Formaldeído , Frutas , Temperatura Alta , Masculino , Camundongos , Morfina/farmacologia , Morfina/uso terapêutico , Contração Muscular , Dor/etiologia , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
This paper describes the antinociceptive effects of tetrahydrophthalimides and related compounds in mice. Twenty compounds were obtained by the reaction of cis-1,2,3,6-tetrahydrophthalic anhydride with appropriate amines, dehydration, and addition to the imidic double bond. They were analyzed in the writhing test at 10 mg/kg given intraperitoneally. The most active compound 2-benzyl-5-morpholin-4-yl-hexahydroisoindole-1,3-dione (19) was studied on formalin, capsaicin, glutamate and hot plate models. The antinociceptive activity demonstrated by some studied compounds is promising, and some of them were more active than acetylsalicylic acid and paracetamol used as reference drugs in writhing tests in mice. Compound 19 was about 5-fold more potent than the reference drugs, being also effective by oral route and against the inflammatory response in the formalin test. The results suggest that compound 19 could be used as a model to obtain new and more potent antinociceptive agents. It exhibits an interesting antinociceptive profile, and does not interact with opioid systems.
Assuntos
Analgésicos/farmacologia , Captana/farmacologia , Ftalimidas/farmacologia , Acetaminofen/farmacologia , Animais , Aspirina/farmacologia , Capsaicina , Formaldeído , Ácido Glutâmico/farmacologia , Temperatura Alta , Indometacina/farmacologia , Masculino , Camundongos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
The object of this study was to give an account of the experiment with a teenage group by using sexual education experiences of their own. Ten workshops were made with low-income teenagers of Município de Aparecida de Goiânia /GO, which happened because of the socialization and reflections about the contents of this study. The work was based on Paulo Freire's Participative Methodology and made better by the attention of the coordinators to every single group, considering their special needs and possibilities. We conclude that for the success of this work, the coordinator must listen to the group with a very sensitive prospect, especially when dealing with a teenage group. It is necessary to stimulate the participation, so that more can be learnt and the citizen work can be able to change its social reality.
Assuntos
Educação em Saúde , Educação Sexual , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , HumanosRESUMO
O objetivo deste estudo foi relatar a experiência com grupo de adolescentes através de oficinas vivenciais sobre educação sexual. Realizamos 10 oficinas com adolescentes de baixa renda do Município de Aparecida de Goiânia/GO, que aconteceram a partir de reflexões e socialização do conhecimento sobre esta temática. O trabalho foi embasado na metodologia participativa de Paulo Freire e potencializado pela atenção dos coordenadores ao movimento do grupo, considerando suas necessidades e possibilidades. Concluímos que para o sucesso do trabalho interativo o coordenador de grupos deve ter uma escuta sensível aos anseios do grupo, especialmente o de adolescente. É necessário estimular a participação para a aquisição de conhecimentos o que favorecerá o exercício da cidadania e transformação da sua realidade social.
The object of this study was to give an account of the experiment with a teenage group by using sexual education experiences of their own. Ten workshops were made with low-income teenagers of Município de Aparecida de Goiânia /GO, which happened because of the socialization and reflections about the contents of this study. The work was based on Paulo Freire's Participative Methodology and made better by the attention of the coordinators to every single group, considering their special needs and possibilities. We conclude that for the success of this work, the coordinator must listen to the group with a very sensitive prospect, especially when dealing with a teenage group. It is necessary to stimulate the participation, so that more can be learnt and the citizen work can be able to change its social reality.
El objetivo de este estudio fue relatar la experiencia con grupo de adolescentes a través de talleres vivenciales sobre educación sexual. Realizamos 10 talleres con adolescentes de bajo poder adquisitivo del Municipio de Aparecida de Goiânia-GO, que se dieron a partir de reflexiones y socialización del conocimiento sobre esta temática. El trabajo fue realizado en base a la metodología participativa de Paulo Freire y potenciado por la atención de los coordinadores del movimiento del grupo, considerando sus necesidades y posibilidades. Concluimos que para el éxito del trabajo interactivo el coordinador de grupos debe tener una escucha sensible a los anhelos del grupo, especialmente de los adolescentes. Es necessário estimular la participación para la adquisición de nuevos conocimientos favoreciendo así el ejercicio de la ciudadanía para transformación de su realidad social.
Assuntos
Adolescente , Humanos , Educação em Saúde , Educação Sexual , Infecções Sexualmente Transmissíveis/prevenção & controleRESUMO
Os Remédios Florais de Bach (RFB), constituem um método alternativo de tratamento usado largamente na terapêutica de várias patologias em muitos países do mundo. Os RFB são reconhecidos como tratamento natural pela OMS desde 1956. Embora o mecanismo de ação dos RFB ainda não tenha sido elucidado, eles vêm sendo indicados para o tratamento de várias doenças neuropsiquiátricas. O objetivo do presente trabalho foi detectar possíveis efeitos centrais dos RFB em modelos farmacológicos utilizados na pesquisa de substâncias com efeitos ansiolíticos, hipnóticos, antidepressivos e neurolépticos. Para tanto, camundongos receberam um tratamento agudo via oral (0,45 mL) 1 hora antes dos testes. Os resultados mostraram que os florais Gorse e, em conjunto, White chestnut, Agrymony e Vervain exibiram perfis antidepressivo e hipnótico, respectivamente. No modelo de ansiedade foi detectado efeito ansiolítico do floral Agrymony. Entretanto, não foram observados efeitos neurolépticos do floral Clematis. Os resultados nos levam a sugerir que os efeitos centrais dos florais avaliados podem ser parcialmente detectados através de modelos farmacológicos utilizados na pesquisa de agentes psicotrópicos.
The Bach Flowers Remedies (BFR's) are worldwide used as an alternative therapeutical approach for several pathologies, being considered by WHO as natural therapy since 1956. Despite the unknown mechanism of action, the BFR's have been widely used on treatment of several neuropsychiatry diseases. Based on pharmacological models used to detect ansiolitic, antidepressant, hypnotic and neuroleptyc effects of different substances, the aim of this work was to evaluate possible central effects of the BFR's. For this purpose, albino mice received BFR's treatment (0.45 mL) by oral route 1 hour prior to each test. The results revealed that the Gorse flower alone and a mix of White chestnut, Agrymony and Vervain showed antidepressant and hypnotic effects, respectively. On the anxiety model, Agrymony showed an ansiolitic effect but no neuroleptyc effects were observed for Clematis floral therapy. The herein described results allow us to conclude that the studied BFR's central effects may be partially detected through pharmacological models currently and widely used on psychotropic agents research.
RESUMO
A new triterpene 3,15-dioxo-21alpha-hydroxy friedelane has been isolated from methanol extract of Maytenus robusta and its structure elucidated on the basis of spectral analysis. Stigmasterol, friedelin, friedelanol and 3,15-dioxo friedelane were also obtained. 3,15-dioxo-21alpha-hydroxy friedelane was analyzed against the writhing test in mice and exhibited potent dose-dependent effects with an ID50 value of 12.5 +/- 2.1 micromol kg(-1) and a maximal inhibition of 85.90%. It was about 10-fold more active than aspirin and paracetamol, used as reference drugs.