RESUMO
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
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
In this study a series of sulphonamides and sulphonyl hydrazones of maleimide, naphthalimide and phthalimide derivatives was synthesized. The antidepressant effect of these compounds was evaluated by the forced-swimming test in mice. The behavioural parameter observed in this test is a reduction in the immobility time, which is indicative of antidepressant activity. All compounds, except 8, 11 and 24, were active as antidepressants. The most active compound was the sulphonyl-hydrazone 10 which showed an activity of around 72.02% at 60 mg/kg, it thus being more active than imipramine (10mg/kg, ip), a commercial antidepressant. Other important results were obtained for the benzylnaphthalimide derivatives, the sulphonamides 21 and 22 showing activity of 64% at 10mg/kg, also being more active than imipramine. These results indicate that the sulphonamides and sulphonyl-hydrazone cyclic imide derivatives are potential compounds for use in the designing of new candidates for the treatment of depression.
Assuntos
Antidepressivos/farmacologia , Hidrazonas/farmacologia , Atividade Motora/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Antidepressivos/síntese química , Antidepressivos/química , Hidrazonas/síntese química , Hidrazonas/química , Masculino , Camundongos , Estrutura Molecular , Estereoisomerismo , Estresse Psicológico , Sulfonamidas/síntese química , Sulfonamidas/química , Natação/psicologiaRESUMO
Magnetic N-benzyl-O-carboxymethylchitosan nanoparticles were synthesized through incorporation and in situ methods and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and magnetization measurements. Indomethacin was incorporated into the nanoparticles via the solvent evaporation method. The indomethacin-loaded magnetic nanoparticles were characterized by the same techniques, and also by transmission electron microscopy. The nanoparticles containing the polymer showed a drug loading efficiency of between 60.8% and 74.8%, and the magnetic properties were not significantly affected by incorporation of the drug. The in vitro drug release study was carried out in simulated body fluid, pH 7.4 at 37°C. The profiles showed an initial fast release, which became slower as time progressed. The percentage of drug released after 5 h was between 60% and 90%, and the best fitting mathematical model for drug release was the Korsmeyer-Peppas model, indicating a Fickian diffusion mechanism.
Assuntos
Quitosana/análogos & derivados , Indometacina/farmacologia , Magnetismo/métodos , Nanopartículas/química , Varredura Diferencial de Calorimetria , Quitosana/síntese química , Quitosana/química , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Cinética , Modelos Químicos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
This study evaluates the effect of complex cross-linked chitosan iron-(III) (CH-FeCL) polymer as phosphate binder in renal failure induced by alloxan (150 mg/kg, i.p.) in rats. The animals (male and female) were divided into four groups and received the treatment once a day for 15 days: (i) control group, which received a single injection of saline (3 ml/kg, i.p.) and normal diet; (ii) alloxan group, which received only a dose of alloxan and normal diet; (iii) phosphate (PO4) group, which received diet supplemented with phosphate 1.2%; and (iv) CH-FeCL group, which received diet supplemented with phosphate 1.2% + CH-FeCL 0.5% (0.054% Fe elemental). It was observed that the CH-FeCL treatment did not alter body-weight, relative weight of the organs and haematological parameters in the treated and control groups for both sexes. However, a decrease in serum phosphorus level of the CH-FeCL group was observed after 15 days, compared with the phosphate group in both sexes. The serum iron concentration of the CH-FeCL group did not differ from the control group in either sex. CH-FeCL polymer decreases intestinal phosphate absorption in rats with renal failure and is promising for the treatment of phosphate retention in patients with renal failure.
Assuntos
Quitosana/farmacologia , Cloretos/farmacologia , Compostos Férricos/farmacologia , Fosfatos/metabolismo , Insuficiência Renal/tratamento farmacológico , Aloxano , Animais , Quitosana/química , Cloretos/química , Reagentes de Ligações Cruzadas , Diabetes Mellitus Experimental/complicações , Feminino , Compostos Férricos/química , Absorção Intestinal/efeitos dos fármacos , Ferro , Masculino , Fosfatos/administração & dosagem , Fósforo/sangue , Ratos , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Fatores SexuaisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Mastrunço (Coronopus didymus--CD) is currently considered as a medicinal specie often used in Brazil, especially in southeast region, for the treatment of several diseases in which pain and inflammation are common. Treatment with the plant can be done by infusion, decoction, or through food. The aim of this study was: to investigate the anti-inflammatory effect of hydroalcoholic extract obtained from the leaves of CD following the traditional procedure. MATERIALS AND METHODS: The anti-inflammatory activity was determined using mouse of pleurisy and paw oedema models, both process being induced by different flogistic agents such as: carrageenan (Cg), bradykinin (BK), histamine (HIS), substance P (SP), dextran (DEX) or prostaglandin E(2) (PGE(2)). We evaluated the effect of CD (200-600 mg/kg) administered by oral route (p.o.) upon leukocytes migration, myeloperoxidase (MPO), and adenosine-deaminase (ADA) activities and nitric oxide (NO) levels. RESULTS: CD (200-600 mg/kg) inhibited the leukocytes by 60.0+/-1.42%, neutrophils by 82.75+/-1.29%, MPO by 42.30+/-4.23%, and ADA activities by 57.89+/-1.94%, as well as NO levels by 64.28+/-2.15% in Cg induced pleurisy. CD also inhibited total and differential leukocytes in the pleurisy induced by BK (1.30+/-0.11/0.29+/-0.02), HIS (1.20+/-0.09/0.42+/-0.05) and SP (0.74+/-0.06/0.14+/-0.01). In addition, CD was effective in reducing paw oedema induced by Cg by 72.79+/-1.13%, SP by 68.26.+/-0.78%, BK by 66.66.+/-0.77%, PGE(2) by 53.346.+/-1.18 and DEX by 65.14+/-2.35%. CONCLUSION: Several mechanisms, including the inhibition of enzymes (MPO and ADA) and mediators (BK, HIS, SP, NO and PGE(2)) release and/or action, appear to account for the anti-inflammatory effect of Coronopus didymus.
Assuntos
Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Pleurisia/tratamento farmacológico , Adenosina Desaminase/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Bradicinina/farmacologia , Brasil , Carragenina/farmacologia , Edema/induzido quimicamente , Histamina/farmacologia , Inflamação/induzido quimicamente , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Camundongos , Neutrófilos/efeitos dos fármacos , Óxido Nítrico/farmacologia , Peroxidase/farmacologia , Folhas de Planta/química , Pleurisia/induzido quimicamente , Ratos , Substância P/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hedyosmum brasiliense Miq. (Chloranthaceae) is an essential Brazilian species largely found in the Atlantic Forest. It is popularly known as "cidrão" and in folk medicine, this aromatic species is widely used as a calmative/tranquilizer and to treat sleep disorders. AIM OF THE STUDY: To examine the neurochemical properties of ethanol extract (EEHb), fractions and compounds of fresh leaves of Hedyosmum brasiliense and the antidepressant effect of the isolated sesquiterpene lactones podoandin and 13-hydroxy-8,9-dehydroshizukanolide. MATERIALS, METHODS AND RESULTS: The effects of EEHb were demonstrated by the open field, elevated-plus-maze, forced swimming, pentobarbital-induced sleeping time, PTZ-induced seizure, and inhibitory avoidance tests. EEHb did not show a protective effect against PTZ-induced convulsions. In the plus-maze test, EEHb (100mg/kg, i.p.) exhibited an anxiolytic effect through the effective enhancement of the frequency and time spent in the open arms of the maze. Conversely, the time spent and the number of entrances to the closed arms were decreased. All these effects were also completely reversed by pre-treatment with flumazenil (2.5mg/kg, i.p./a benzodiazepine receptor agonist), similar to the results observed with diazepam used as a positive standard. In this test, the anxiolytic effect of EEHb was also totally blocked by pre-treatment with reserpine (2.0mg/kg, i.p.), a drug known to induce depletion of biogenic amines. In the forced swimming test, the treatment of EEHb (100mg/kg, i.p. or 100mg/kg, p.o.) given in acute and chronic form (10, 50 and 100mg/kg), produced a decrease in immobility time, similar to that of imipramine (10mg/kg, i.p.), the positive control. The dichloromethane and hexane fractions (100mg/kg, p.o.) also produced a decrease in immobility time. In addition, the two isolated compounds tested in a single dose (10mg/kg, i.p.), the antidepressant effect was observed only with the compound podoandin, which also caused a decrease in immobility time. EEHb (10-100mg/kg) a dose-dependent manner also caused a decrease in barbiturate sleeping time in mice, and in high doses (100mg/kg), did not interfere in memory consolidation. CONCLUSIONS: The results suggest that EEHb presents psychopharmacological activities, including anxiolytic, antidepressant, and hypnotic effects.
Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Magnoliopsida/química , Sesquiterpenos/farmacologia , Animais , Aprendizagem da Esquiva , Relação Dose-Resposta a Droga , Lactonas/farmacologia , Masculino , Aprendizagem em Labirinto , Camundongos , Ratos , Ratos Wistar , Sesquiterpenos/químicaRESUMO
The antinociceptive effect of the limonexic acid isolate of Raulinoa echinata Cowan in four models of pain in mice is described. When evaluated against acetic acid-induced abdominal constrictions, limonexic acid (10, 30 and 60 mg kg(-1), i.p.) produced dose-related inhibition of the number of constrictions, with a mean ID50 value of 43 (2.3-79) micromol kg(-1), and was more potent than some standard drugs. In the formalin test, limonexic acid inhibited both the first and second phases of formalin-induced pain. Furthermore, the effect was more pronounced in the second phase, with a mean ID50 value of 13.66 (9.35-19.61) micromol kg(-1), and had a pharmacological profile that was similar to standard drugs such as acetaminophen and acetyl salicylic acid. Limonexic acid also produced dose-related inhibition of glutamate- and capsaicin-induced pain, with mean ID50 values of 11.67 (8.51-16.0) micromol kg(-1) and 47.17 (36.51-60.93) micromol kg(-1), respectively. The mechanism of action is not completely understood, but seems to involve direct interaction with the GABAergic and nitroxidergic pathways.
Assuntos
Analgésicos/farmacologia , Limoninas/farmacologia , Dor/tratamento farmacológico , Rutaceae/química , Acetaminofen/administração & dosagem , Acetaminofen/farmacologia , Analgésicos/administração & dosagem , Animais , Aspirina/administração & dosagem , Aspirina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Limoninas/administração & dosagem , Masculino , Camundongos , Neurônios Nitrérgicos/efeitos dos fármacos , Neurônios Nitrérgicos/metabolismo , Medição da Dor , Fitoterapia , Extratos Vegetais , Raízes de Plantas , Caules de Planta , Ácido gama-Aminobutírico/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10 +/- 0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39 +/- 0.37 and 0.68 +/- 0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r = 0.764; p < 0.0001). The concentration of SAA in transudates was low and did not overlap with that found in exudates (0.02-0.21 versus 0.8-360.5 g/mL). SAA in pleural and ascitic exudates results mainly from leakage of the serum protein via the inflamed membrane. A comparison of the E/S ratio of SAA and CRP points SAA as a very good marker in discriminating between exudates and transudates.
Assuntos
Proteínas de Fase Aguda/metabolismo , Proteína C-Reativa/metabolismo , Exsudatos e Transudatos/metabolismo , Proteína Amiloide A Sérica/metabolismo , Ascite/metabolismo , Biomarcadores/metabolismo , Proteínas Sanguíneas/metabolismo , Humanos , Derrame Pleural/metabolismo , Sensibilidade e Especificidade , Fatores de TempoRESUMO
PURPOSE: The present study was carried out to evaluated acute and subacute toxicity of a hydroalcoholic extract from aerial parts of Wedelia paludosa (Asteraceae). METHODS: Toxicity of W. paludosa was evaluated in Swiss mice after ingestions of the extract during one day (acute model) and during 15 days (subacute model). RESULTS: The results showed that the LD50 of the extract is higher than 4000 mg/kg and the subacute treatment did not shows any change in corporal weight and hematological parameters. However, a change in liver weight but not in hepatic enzymes was observed. This suggests that the liver function is not altered by Wedelia paludosa in this study. Some changes in the creatinine content were observed, but could not be related with the extract dose. CONCLUSIONS: The results suggest that the plant seems to be destituted of toxic effects in mice.
Assuntos
Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Wedelia , Animais , Asteraceae , Etanol/administração & dosagem , Etanol/toxicidade , Feminino , Masculino , Camundongos , Componentes Aéreos da Planta , Água/administração & dosagemRESUMO
We evaluated the variation of the concentration of kaurenoic acid (1), which is a bioactive diterpene, in leaves, flowers, stems and roots from Wedelia paludosa (Acmela brasiliensis) for different seasons using the HRGC/FID method. The results indicated that the concentration of 1 is higher in the roots and stems during the autumn. The pharmacological results suggested that kaurenoic acid is responsible, at least in part, for the hypoglycemic potential detected in this plant.
Assuntos
Glicemia/metabolismo , Diterpenos/análise , Diterpenos/farmacologia , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Extratos Vegetais/análise , Wedelia/química , Animais , Glicemia/efeitos dos fármacos , Diterpenos/metabolismo , Teste de Tolerância a Glucose , Glibureto/farmacologia , Hiperglicemia/sangue , Masculino , Ratos , Ratos Wistar , Estações do AnoRESUMO
Resultados obtidos anteriormente pelo nosso grupo mostraram que a proteína de fase aguda amilóide sérica A (SAA) é um potente estímulo para a expressão de mRNA e liberação de TNF- alfa, IL-1-ß e Il-8 em leucócitos humanos, além de atuar como priming para a lberação de espécies reativas de oxigênio (EROs) por neutrófilos. Nosso objetivo, nesse trabalho, foi mostrar a presença de SAA em exsudatos e definir sua origem, além de verificar sua atividade pró-inflamatória in vivo. Para tanto, utilizamos soro e exsudatos pleurais de 32 pacientes com pneumonia. Mostramos primeiramente a presença da SAA no material inflamatório através de SDS-PAGE, immunoblotting e HPLC. A quantificação de SAA nas amostras foi realizada por ELISA...