Phytochemical, antioxidant, anti-stress and cerebroprotective activity of ethanolic extract of stem of Sarcostemma acidum

The current study was designed to assess the phytochemical, antioxidant, anti-stress and cerebroprotective activities of ethanolic extract of stem of Sarcostemma acidum (EESA). The stem of Sarcostemma acidum was collected and extracted with 70% ethanol. The ethanolic extract was subjected to phytochemical screening (Chemical and HPTLC), antioxidant (in-vitro), anti-stress (Mice model) and cerebroprotective activities (Cerebral ischemia model). EESA showed presence of flavonoids as primary phytoconstituents. EESA significantly reduced the immobility period in tail suspension trial and swimming endurance trial. EESA significantly reduced the TBARS levels (21.45±0.56; p<0.01) and augmented tissue antioxidants in cerebral ischemia model. The levels of MOA-A were reduced in the EESA treated animals (54.1±0.2; p<0.001) and cortisol levels also reduced in EESA treated animals (45.1±1.6; p<0.001). Histopathology also supported the biochemical parameters. The EESA effect was compared with reference standard diazepam and Ashwagandha. EESA showed significant antioxidant, anti-stress and cerebroprotective activities and the protective effect might be due to presence of flavonoids as phytoconstituents.

Antidepressant like activity of Buspirone but not ondensetron in combination with Fluoxetine or Desipramine in mice

Background: The involvement of one or more 5-HT receptor sub-types in the pathophysiology of depression is still unclear. The study was performed to investigate the effect of ondansetron and buspirone on depression, and their interaction with fluoxetine or desipramine.Methods: The mice were administered ondansetron, buspirone alone and in combinations with fluoxetine or desipramine for 21 days, and the antidepressant effect was assessed by the immobility period and the sucrose consumption, on the tail suspension test (TST) and the chronic mild stress (CMS) models, respectively.Results: Both ondansetron and buspirone when given alone demonstrated slight non-significant decrease in the immobility time. Ondensetron when given in combination with fluoxetine (10 mg/kg; i.p.) and desipramine (15 mg/kg; i.p.), showed significant decrease in immobility time in comparison to the control group only. On the other hand, both the combinations of buspirone, either with fluoxetine or desipramine showed significant decrease in the immobility time when compared to the respective group. In CMS, the fluoxetine, desipramine, ondansetron, and buspirone showed gradual increase in the sucrose consumption, at the end of 4th, 5th, and 6th week, but the significant effect was observed only at the end of 6th week, as compared to the control. The combination of buspirone with desipramine but not with fluoxetine showed significant increase in sucrose consumption when compared to respective group.Conclusions: Therefore, the study indicates that both buspirone and ondansetron have a potential antidepressant like action, although buspirone has shown better antidepressant activity than ondansetron as observed in various combination groups.

Preclinical evaluation of the impact of cilostazol on anti-depressant activity of fluoxetine

The current anti-depressant agents have limitations like the slow onset of action, moderate efficacy, withdrawal symptoms, incompliance of treatment, and instabilities in circadian rhythm. Their therapeutic use is quite restricted and produces inadequate or partial symptomatic relief of depression which may lead to treatment- resistance depression. In the view of a new strategy, second messengers (cAMP, cGMP) and their signalling pathways are emerging as novel targets for anti-depressants. The present study conducted to evaluate the augmentation property of cilostazol on the anti-depressant activity of fluoxetine. Traditional anti-depressant models like forced swimming test and tail suspension test were employed. Mice were randomly grouped into six groups, with six rats in each. Each group was treated, as mentioned in the study. The reduction in immobility period of each mouse was noted. These results were analysed by ordinary one way ANOVA followed by Tukey’s multiple comparison test. Cilostazol at a dose of 20 mg/kg i.p significantly reduced immobility period when compared to cilostazol 10 mg/kg i.p and normal saline. Cilostazol 10 mg/kg i.p also decreased immobility period significantly when compared to normal saline by forced swimming test. Fluoxetine 20 mg/kg i.p + cilostazol 20 mg/kg i.p produced a highly significant reduction in the immobility period in comparison with all groups except with fluoxetine 20 mg/kg i.p + cilostazol 10 mg/kg i.p in forced swimming test. This study concludes that cilostazol has produced dose-dependent anti-depressant activity. This study also emphasises cilostazol can augment the anti-depressant activity of fluoxetine.

Anti-stress activity of Ocimum sanctum and alprazolam in animal models

Background: Stress is the physiological, psychological and behavioral response by individuals when they perceive a lack of equilibrium between the demands placed upon them and their ability to meet those demands, which over a period of time leads to ill health. There are several ways of coping with stress. Some techniques of time management may help a person to control stress.Methods: Forced swim test- mice were randomized into two groups according to the body weights. Each group contains six animals. Each individual animal was allowed to swim inside the jar (25-12-25 cm) containing fresh water up to 15 cm height. Mice were allowed swim for 6 min. After initial struggle to escape the animal became immobile. Total immobility period was measured. Rotarod test- mice were randomized into two groups according to body weights. Each group contains six animals. Rats were placed on the lanes. Latency period was recorded at which each rat falls off the rod.Results: In first experiment, anti-stress activity of Ocimum sanctum in mice was demonstrated by measuring the immobility period during forced swim test and in the second experiment the measurement of the latency period of rats in rotarod apparatus was performed. Both the experimental procedures were compared with standard anti stress drug alprazolam.Conclusions: The present study suggests that Ocimum sanctum possess significant anti stress activity but less when compared to alprazolam.

Potentiation of Antidepressant Effects of Agomelatine and Bupropion by Hesperidin in Mice

Hesperidin, a well-known flavanone glycoside mostly found in citrus fruits, showed neuroprotective and antidepressant activity. Agomelatine, a melatonergic MT1/MT2 agonist and 5-HT2C receptor antagonist, exhibits good antidepressant efficacy. Bupropion has been widely used for the treatment of depression because of its dopamine and norepinephrine reuptake inhibition. The objective of present study was to assess the antidepressant effects of hesperidin combination with agomelatine or bupropion. Male Swiss Albino mice received treatment of saline, vehicle, ‘hesperidin alone’, ‘agomelatine alone’, hesperidin+agomelatine, ‘bupropion alone’, hesperidin+bupropion, and agomelatine+bupropion for 14 days. The immobility period was analysed 30 min after the treatment in forced swim and tail suspension tests. Dopamine and serotonin levels were analysed in hippocampus, cerebral cortex, and whole brain using HPLC with fluorescence detector. Hesperidin plus agomelatine treated group was better in terms of decrease in immobility period and increase in dopamine and serotonin levels when compared to their respective monotherapy treated groups.

NEUROCHEMICAL ASSESSMENT AND BEHAVIORAL ROLE OF TUBEROINFUNDIBULAR PEPTIDE-39 IN ACUTE RESTRAINT STRESS-INDUCED DEPRESSION IN RATS.

Objective: Tuberoinfundibular peptide of 39 (TIP39) is a potent agonist to the parathyroid hormone 2 receptor (PTH2R) abundantly expressed in brain. The current study focused to evaluate the role of TIP39 in acute restraint stress (ARS)-induced depression model.Methods: Rats were exposed to ARS for 2 h to establish the depression and then subjected to open field and forced swim test (OFT and FST). TIP39 (1 and 10 nmol/rat) and HYWH (1 nmol/rat) are a PTH2R antagonist which was infused through intracerebroventricular route. Diazepam (2 mg/kg, i.p) was utilized as reference standard.Results: The results depict ARS significantly diminished the TIP39 expression in cerebral regions and causes depression-like behavior. TIP39 significantly decreased the immobility period in FST. In the OFT, TIP39 significantly increased the ambulatory activity and did not alter the rearing and grooming activity in comparison to ARS group. After TIP39 treatment, plasma noradrenaline levels were significantly increased, whereas the serotonin levels were unaltered. The corticosterone levels also decreased significantly. In rat brain tissues, TIP39 significantly reversed the abnormalities in glutamate and gamma-aminobutyric acid (GABA) level by ARS induction. In contrast, HYWH-treated rats did not show any significant variations in the neurochemical and behavioral parameters in comparison to ARS rats.Conclusion: Our reports submitted that the primary evidence depicting the stimulation of TIP39 expression could modulate the monoaminergic, GABAergic, and glutaminergic release with the support of hypothalamic-pituitary-adrenal axis that can be produced an antidepressant-like effect evident with the interactive study.

NEUROCHEMICAL ASSESSMENT AND BEHAVIORAL ROLE OF TUBEROINFUNDIBULAR PEPTIDE-39 IN ACUTE RESTRAINT STRESS-INDUCED DEPRESSION IN RATS.

Objective: Tuberoinfundibular peptide of 39 (TIP39) is a potent agonist to the parathyroid hormone 2 receptor (PTH2R) abundantly expressed in brain. The current study focused to evaluate the role of TIP39 in acute restraint stress (ARS)-induced depression model.Methods: Rats were exposed to ARS for 2 h to establish the depression and then subjected to open field and forced swim test (OFT and FST). TIP39 (1 and 10 nmol/rat) and HYWH (1 nmol/rat) are a PTH2R antagonist which was infused through intracerebroventricular route. Diazepam (2 mg/kg, i.p) was utilized as reference standard.Results: The results depict ARS significantly diminished the TIP39 expression in cerebral regions and causes depression-like behavior. TIP39 significantly decreased the immobility period in FST. In the OFT, TIP39 significantly increased the ambulatory activity and did not alter the rearing and grooming activity in comparison to ARS group. After TIP39 treatment, plasma noradrenaline levels were significantly increased, whereas the serotonin levels were unaltered. The corticosterone levels also decreased significantly. In rat brain tissues, TIP39 significantly reversed the abnormalities in glutamate and gamma-aminobutyric acid (GABA) level by ARS induction. In contrast, HYWH-treated rats did not show any significant variations in the neurochemical and behavioral parameters in comparison to ARS rats.Conclusion: Our reports submitted that the primary evidence depicting the stimulation of TIP39 expression could modulate the monoaminergic, GABAergic, and glutaminergic release with the support of hypothalamic-pituitary-adrenal axis that can be produced an antidepressant-like effect evident with the interactive study.

INFLUENCE OF GENDER DIFFERENCE IN THE ANTIDEPRESSANT EFFECT OF FLUOXETINE IN MICE IN TAIL SUSPENSION TEST

ABSTRACTAim: To determine the effect of gender difference in the antidepressant effect of fluoxetine (FLX) in mice in tail suspension test (TST).Methods: Swiss albino mice of either sex were used and the depression-like behavior was measured by TST.Results: The present study showed that there was a significant difference in the immobility period of male mice and female mice in TST. However, theantidepressant effect of FLX differs significantly in male mice and female mice in TST.Conclusion: It has been concluded that the antidepressant effect of FLX in TST was affected by the gender difference as suggested by the results ofthe present study.Keywords: Depression, Estrogen, Female, Fluoxetine, Mice, Serotonin.

Efficacy of Ocimum sanctum for Relieving Stress: A Preclinical Study

ABSTRACT History and objective The aim of this study was to study the anxiolytic effects of Ocimum sanctum stress-induced anxiety. Materials and methods The study was carried out using male albino rats (200 ± 50 gm), male albino mice (25 ± 100) the effect of O. sanctum evaluated for anxiety and depression using forced swim test FST and rotarod test. Results Restraint stress (3 hours/day for six consecutive days) induced a significant reduction. It was significantly decreases the mobility period during stress. The standard deviation values are 14.4 and 9.26 and is statistically significant (p = 0.001). In rotarod test, (a) increased latency and (b) decreased ambulation and rearing were also reversed by O. sanctum. A significant increase in immobility period was observed in FST and TST after restraint stress. O. sanctum and C. sinensis significantly reduced the immobility times of rats in FST and TST. Conclusion Ocimum sanctum possess significant antistress activity but the magnitude and efficacy for relieving stress is less, when compare to standard anxiolytic agent, i.e. Alprazolam. How to cite this article Bathala LR, Rao CV, Manjunath SM, Vinuta S, Vemulapalli R. Efficacy of Ocimum sanctum for Relieving Stress: A Preclinical Study. J Contemp Dent Pract 2012;13(6):782-786.