RESUMO
This study was designed to evaluate antidepressant-like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant-like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress-induced decrease in sucrose preference, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress-induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress-induced increase in MAO-A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO-A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.
Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Ácido Gálico/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Corticosterona/sangue , Depressão/metabolismo , Fluoxetina/farmacologia , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Nitritos/sangue , Sacarose/metabolismo , NataçãoRESUMO
BACKGROUND: The aim of present study was to evaluate antidepressant-like activity of ellagic acid in Swiss young male albino mice; and to explore the possible underlying mechanisms for this activity. METHODS: Mice were immobilized for 150 min once only for induction of stress. Ellagic acid (8.75, 17.5, 35 mg/kg, po) and fluoxetine (20 mg/kg, ip) per se were administered to unstressed and stressed mice; and immobility periods were recorded using tail suspension test and forced swim test. The plasma nitrite levels were also estimated in unstressed and stressed mice. Effects of 7-nitroindazole (nNOS inhibitor), aminoguanidine (iNOS inhibitor), prazosin (α(1)-adrenoceptor antagonist), sulpiride (selective D(2)-receptor antagonist), and p-chlorophenylalanine (p-CPA - tryptophan hydroxylase inhibitor) on antidepressant-like activity of ellagic acid were also evaluated. RESULTS: Ellagic acid (17.5 and 35 mg/kg, po) and fluoxetine per se significantly decreased immobility periods of unstressed and stressed mice, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice. Ellagic acid significantly decreased the plasma nitrite levels in stressed mice only. Aminoguanidine significantly potentiated antidepressant-like activity and plasma nitrite decreasing effect of ellagic acid (35 mg/kg) in stressed mice. 7-Nitroindazole did not enhance antidepressant-like activity and plasma nitrite decreasing effect of ellagic acid in unstressed mice. Prazosin and p-CPA significantly attenuated antidepressant-like effect of ellagic acid (35 mg/kg) in unstressed mice only. CONCLUSION: Thus, ellagic acid showed antidepressant-like activity in unstressed mice probably by interaction through adrenergic and serotonergic systems. On the other hand, antidepressant-like activity of ellagic acid in stressed mice might be through inhibition of inducible NOS.
Assuntos
Antidepressivos/farmacologia , Ácido Elágico/farmacologia , Emoções/efeitos dos fármacos , Estresse Psicológico/sangue , Estresse Psicológico/tratamento farmacológico , Animais , Fenclonina/farmacologia , Fluoxetina/farmacologia , Guanidinas/farmacologia , Elevação dos Membros Posteriores/métodos , Imobilização/efeitos adversos , Imobilização/métodos , Indazóis/farmacologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Nitritos/sangue , Prazosina/farmacologia , Restrição Física/efeitos adversos , Restrição Física/métodos , Sulpirida/farmacologia , NataçãoRESUMO
AIMS: In this study, antidepressant-like activity of Emblica offcinalis Gaertn. fruits (Family: Euphorbiaceae) was evaluated in Swiss young male albino mice employing tail suspension test and forced swim test. METHODS: Aqueous extract (200 and 400 mg/kg) of the fruits was administered orally for 14 successive days to mice. On day 14, 60 min after extract administration, animals were subjected to tail suspension test and forced swim test. RESULTS: The extract significantly decreased immobility period in both tail suspension test and forced swim test, indicating significant antidepressant-like activity. The lower dose (200 mg/kg) of the extract showed better antidepressant-like action. The efficacy of the extract was found to be comparable to fluoxetine (20 mg/kg), imipramine (15 mg/kg), and phenelzine (20 mg/kg). The extract did not show any significant effect on locomotor activity of the mice. Prazosin (alpha(1) -adrenoceptor antagonist), sulpiride (selective D(2) -receptor antagonist), baclofen (GABA(B) agonist), and p-CPA (tryptophan hydroxylase inhibitor) significantly attenuated the extract-induced antidepressant-like effect. The extract also significantly decreased brain MAO-A levels. DISCUSSION: The aqueous extract might produce antidepressant-like effect by interaction with α(1)-adrenoceptors, dopamine D(2)- receptors, serotonergic, and GABA(B) receptors. In this study, aqueous extract was found to contain 2.94% of ascorbic acid. So ascorbic acid and other constituents like flavanoids, tannoid principles, and polyphenolic substances present in the aqueous extract of E. officinalis might be responsible for its antidepressant-like activity. CONCLUSIONS: Thus, aqueous extract of E. officinalis showed antidepressant-like activity probably by inhibiting MAO-A and GABA; and also due to its antioxidant activity.
Assuntos
Monoaminas Biogênicas/metabolismo , Depressão , Frutas/química , Phyllanthus emblica , Fitoterapia , Preparações de Plantas/uso terapêutico , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ácido Ascórbico/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Elevação dos Membros Posteriores/métodos , Masculino , Camundongos , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Preparações de Plantas/química , Natação/psicologia , Fatores de Tempo , Ácido gama-Aminobutírico/metabolismoRESUMO
The aim of present study was to evaluate antianxiety-like activity of gallic acid in Swiss young male albino mice; and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and alprazolam (0.25 mg/kg, i.p.) were administered for 10 successive days to separate groups of mice. On 10th day, 45 min after the drug administration, stress was produced by immobilization of mice for 150 min and these mice were called as stressed mice. Anxiolytic activity was evaluated using elevated plus maze and light-dark test. The plasma nitrite and corticosterone levels were also estimated in unstressed and stressed mice. Effects of 7-nitroindazole (neuronal NOS inhibitor) and aminoguanidine (inducible NOS inhibitor) on antianxiety-like activity of gallic acid were also evaluated. Gallic acid (10 and 20 mg/kg) and alprazolam per se significantly showed antianxiety-like activity in both unstressed and stressed mice. The drugs did not show any significant effect on locomotor activity of the mice. Gallic acid significantly decreased the plasma nitrite levels in both unstressed and stressed mice. 7-nitroindazole and aminoguanidine significantly enhanced antianxiety-like activity and plasma nitrite decreasing effect of gallic acid in unstressed and stressed mice respectively. Plasma corticosterone levels were significantly decreased by gallic acid in stressed mice as compared to its control. Thus, gallic acid showed antianxiety-like activity in unstressed mice probably by inhibition of nNOS. On the other hand, antianxiety-like activity in stressed mice might be through inhibition of iNOS and reduction of plasma corticosterone levels.