Antidepressant-like activity of ethanol extract of leaves of Caesalpinia pulcherrima in unstressed and stressed mice

In the present study, antidepressant-like activity of ethanol extract of leaves of Caesalpinia pulcherrima was evaluated in Swiss young male albino mice. Stress was induced in mice by subjecting them to unpredictable mild stress for 21 successive days. Ethanol extract of the leaves (100, 200 and 400 mg/ kg, p.o.) and fluoxetine (20 mg/kg, p.o.) were administered for 21 consecutive days to separate groups of unstressed and stressed mice. Ethanol extract (200 and 400 mg/kg) and fluoxetine significantly decreased immobility period of unstressed as well as stressed mice in tail suspension test (TST). However, the lowest dose (100 mg/kg) of the extract also significantly decreased immobility period of stressed mice in TST. The extract significantly restored reduced sucrose preference in stressed mice. There was no significant effect on locomotor activity of mice. Ethanol extract of the leaves significantly decreased plasma nitrite and corticosterone levels; brain MAO-A activity and MDA level; and increased brain reduced glutathione and catalase activity in unstressed as well as stressed mice as compared to their respective vehicle treated controls. Thus, ethanol extract of leaves of Caesalpinia pulcherrima showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO-Aactivity, reduction of oxidative stress and plasma corticosterone levels.

GABAergic and nitriergic influence in antianxiety-like Activity of Garlic in Mice.

Objectives: To investigate the GABAergic and nitriergic mechanism involved in the anxiolytic-like profile of ethanolic extract of garlic (GE). Materials and Methods: Male Swiss albino mice were employed in the present study. Stress was produced in mice by immobilizing them for 6h. Elevated plus maze, light/dark box and social interaction test were used for the assessment of anxiety in mice. Concentrations of GABA in brain and nitrite level in plasma were estimated to determine the possible involvement of GABAergic and nitriergic mechanisms in the anxiolytic profile of GE. Results: The present study showed that the GE produced significant antianxiety- like activity in unstressed and stressed mice. In unstressed mice, GE significantly increased GABA levels, but could not produce any change in nitrite levels. Meanwhile, in stressed mice, GE significantly increased GABA levels along with a significant decrease in nitrite levels. Pre-treatment with aminoguanidine, an inducible nitric oxide synthase inhibitor, significantly enhanced the anxiolytic-like activity of GE, as compared to GE and aminoguanidine alone in stressed mice, but not in unstressed mice. On the other hand, pretreatment with 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, did not produce any significant change in antianxiety- like activity of GE in unstressed as well as stressed mice. Conclusion: It has been concluded that the garlic may possess anxiolytic- like activity and possess NOS inhibiting property in stressed mice, which may add to its status to be used in stress-induced anxiety conditions.

Punarnavine, an alkaloid isolated from ethanolic extract of Boerhaavia diffusa Linn. reverses depression-like behaviour in mice subjected to chronic unpredictable mild stress.

Punarnavine (20 and 40 mg/kg) and fluoxetine (20 mg/kg) per se administered orally for 14 successive days significantly decreased immobility periods of both unstressed and stressed mice in forced swim test. These drugs also significantly decreased sucrose preference in both stressed and unstressed mice as compared to their respective controls, indicating significant antidepressant-like activity. The drugs did not show any significant effect on locomotor activity of mice. The alkaloid also significantly decreased monoamine oxidase (MAO-A) activity, malondialdehyde levels in both unstressed and stressed mice; and significantly reversed the stress-induced decrease in reduced glutathione and catalase activity. It also significantly attenuated the stress-induced increase in plasma nitrite and corticosterone levels. Thus, punarnavine showed antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO-A activity, decrease in plasma nitrite levels and due to its antioxidant activity. In addition, punarnavine also showed antidepressant-like activity in stressed mice possibly through decrease in plasma corticosterone levels.

Antidepressant-like Activity of Celastrus paniculatus Seed Oil in Mice Subjected to Chronic Unpredictable Mild Stress.

Aims: The present study was done to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil in Swiss young albino mice subjected to chronic unpredictable mild stress. Study Design: Prospective. Place and Duration of Study: Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India, between August 2012 to February 2013. Methodology: The behavioral models such as forced swim test (FST) and sucrose preference test were used to evaluate the effect of seed oil on depression in mice. The oil (50, 100 and 200 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) per se were administered for 14 successive days to unstressed and stressed mice. The effect of oil on locomotor activity of mice was also evaluated. In addition, the effects of oil on brain monoamine oxidase-A, malondialdehyde levels, reduced glutathione and catalase activities; and plasma corticosterone and nitrite levels were also assessed. Results: The oil significantly decreased immobility period of both unstressed and stressed mice in FST as compared to the control. The oil also prevented the stressinduced decrease in sucrose preference, indicating significant antidepressant-like activity There was no significant effect on locomotor activity of mice by the oil. Antidepressant-like activity of the oil was comparable to the standard drug, fluoxetine. The oil also significantly decreased monoamine oxidase-A (MAO-A) activity, malondialdehyde levels in both unstressed and stressed mice; and significantly prevented stress-induced decrease in reduced glutathione and catalase activities. It also significantly attenuated stress inducedincrease in plasma nitrite and corticosterone levels. Conclusion: Celastrus paniculatus seed oil showed significant antidepressant-like activity in both unstressed and chronic unpredictable mild stressed mice probably due to inhibition of MAO-A activity, decrease in plasma nitrite levels; and through scavenging of free radicals. In addition, the oil also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

Behavioural and neuroendocrine effects of aqueous extract of Boerhaavia diffusa Linn. in mice using tail suspension and forced swim tests – A preliminary study.

The present study was done to evaluate the effect of aqueous extract of B. diffusa on depression in mice using behavioral models such as tail suspension test (TST) and forced swim test (FST). The extract (50, 100 and 200 mg/kg, po) was administered for 14 successive days to Swiss young albino mice. On 14th day, 60 min after administration, mice were subjected to TST and FST. The administration of aqueous extract of B. diffusa (50, 100 and 200 mg/kg, po) significantly decreased immobility period in both TST and FST, indicating significant antidepressant-like activity. The lowest dose (50 mg/kg) of the extract decreased the immobility period most significantly in FST, showing most potent antidepressant-like action. The efficacy of the extract (50 mg/kg) was comparable to fluoxetine (20 mg/kg). The extract did not show any significant effect on locomotor activity. The extract showed significant monoamine oxidase -A inhibitory activity. There was no significant effect of the extract on plasma corticosterone levels. Prazosin (α1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABAB agonist), and p-CPA (tryptophan hydroxylase inhibitor) significantly attenuated the extract-induced antidepressant-like effect, when tested in TST. The extract might produce antidepressant-like effect by interaction with α1-adrenoceptors, dopamine-D2 receptors, serotonergic, and GABAB receptors. Thus, aqueous extract of B. diffusa showed significant antidepressant-like activity in mice probably through involvement of monoaminergic and GABAergic systems.

Differential effects of nitric oxide synthase inhibitors on anxiety in unstressed and stressed mice.

Effects of selective nitric oxide synthase (NOS) inhibitors, 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (nNOS) and aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on anxiety in unstressed and stressed mice were investigated using elevated plus maze (EPM) test and light-dark test (LDT). 7-NI (20 and 40 mg/kg, ip) produced anti-anxiety effect in unstressed mice but not in stressed mice. AG (50 and 100 mg/kg, ip) produced anxiolytic effect in stressed mice and failed to produce the similar effect in unstressed mice. Nitrite levels were increased in stressed mice, but not in unstressed mice, exposed to EPM and LDT for 5 min. Increased nitrite levels in stressed mice were attenuated by AG, but not by 7-NI. The effects of AG were enhanced by pyrrolidine-dithio-carbamate (PDTC), an inhibitor of NF-κB induction, in stressed mice. The results suggest the possible role of inducible nitric oxide synthase in stress-induced anxiogenesis as compared to unstressed mice, where neuronal form of NOS may plays pre-dominant role.

Inhibition of MAO and GABA: probable mechanisms for antidepressant-like activity of Nardostachys jatamansi DC. in mice.

Ethanolic extract (100, 200 and 400 mg/kg, po) of N. jatamansi administered for 14 successive days to Swiss young albino mice (either sex) produced significant antidepressant-like effect in both tail suspension and forced swim tests. The efficacy of the extract was found to be comparable to imipramine (15 mg/kg, po) and sertraline (20 mg/kg, po). Ethanolic extract (200 mg/kg, po) did not show any significant change on locomotor activity of mice as compared to control; hence it did not produce any motor effects. Further, the extract decreased the whole brain MAO-A and MAO-B activities as compared tocontrol, thus increased the levels of monoamines. The antidepressant effect of the extract was also significantly reversed by pretreatment of animals with baclofen (GABAB agonist); when tested in tail suspension test. The results suggested that the antidepressant-like effect of the extract may also be due to interaction with GABAB receptors, resulting in decrease in the levels of GABA in mouse brain. Thus, the extract may have potential therapeutic value for the management of mental depression.

Evaluation of antidepressant-like activity of aqueous and ethanolic extracts of Terminalia bellirica Roxb. fruits in mice.

The present study was undertaken to investigate the effect of aqueous and ethanolic extracts of T. bellirica on depression in mice using forced swim test (FST) and tail suspension test (TST). The extracts were administered orally for 10 successive days in separate groups of Swiss young male albino mice. Aqueous extract (50, 100 and 200 mg/kg) in a dose-dependent manner and ethanolic extract (100 mg/kg) significantly reduced the immobility time of mice in both FST and TST. The extracts were without any significant effect on locomotor activity of mice. The efficacies of aqueous extract (200 mg/kg) and ethanolic extract (100 mg/kg) were found to be similar to that of imipramine (15 mg/kg, po) and fluoxetine (20 mg/kg, po) administered for 10 successive days. Both extracts reversed reserpine-induced extension of immobility period of mice in FST and TST. Prazosin (62.5 microg/kg, ip; an alpha1-adrenoceptor antagonist), sulpiride (50 mg/kg, ip; a selective D2 receptor antagonist) and p-chlorophenylalanine (100 mg/kg, ip; an inhibitor of serotonin synthesis) significantly attenuated the aqueous and ethanolic extract-induced antidepressant-like effect in TST. Thus, both the aqueous and ethanolic extracts of T. bellirica elicited a significant antidepressant-like effect in mice by interaction with adrenergic, dopaminergic and serotonergic systems.