Anti-depressant Activity of Hydroalcoholic Extract of Asperula odorata L. in Mice

Background: The relationship between the treatment of depression and plant-derived substances (e.g., flavonoids, coumarin, and scopoletin) has been demonstrated through interference with the monoamine system. The present study was planned to evaluate the anti-depressant effects of Asperula odorata L. plant through behavioral tests in mice. Material and Methods: In this experimental study, 35 male Syrian mice weighing 30-40 g were examined in five groups (n=7) as follow: received oral distilled water gavage (control), 10 mg/kg of fluoxetine solution gavage (reference standard), 10, 5, and 2.5 mg/kg of A. odorata L. extract gavage (treatment groups). After one week, all behavioral tests, including tail suspension test (TST), forced swimming test (FST), open field test (OFT), elevated plus maze test (EPMT), and fractionation tests were performed each morning for 4-6 h within five days. Results: The hydroalcoholic extract of A. odorata contained phenolic and flavonoid substances (Shinoda test confirmed flavonoid family). Administration of extract (10 and 5 mg/kg doses) versus fluoxetine (10 mg/kg dose) reduced the immobility of animals in both FST and TST (P<0.05). At the OFT, the administered extract increased the number of central square entries of animals with higher mobility (P<0.05). At a 10 mg/kg dose, the active flavonoid ingredients increased the mice's incline to entre and spent more time within no wall parts of EPMT (P<0.05). Conclusion: Our study suggests that the hydroalcoholic extract of A. odorata L. could have significant anti-depressant activity. [GMJ.2021;10:e2206]

Anxiolytic effect of the homeopathic complex Tepeex®

Aims: Homeopathic complex Tepeex® is a compound of Actaea racemosa 4cH, Natrum muriaticum 2cH, Pulsatilla nigricans 3cH, Chamomilla 3cH and Sepia succus5cH. This study evaluated the effect of Tepeex® in pre-clinical models of depression and anxiety. Methods: the following tests were performed: elevated plus maze test (EPM); forced swimming test (FST); open field test (OFT) and Rotarod test (RRT). Results: In EPM, animals treated with Tepeex® on days 20 and 30 stayed longer in the open arms of the maze than the control group (p < 0.05, Dunnett test). In FST, treatment with Tepeex® did not increase swimming time compared to the control group in any phase of treatment. In OFT, crossing increased significantly with treatment with amfepramone, and also with 30-day treatment with Tepeex® (p < 0.05, Dunnette test). In RRT, treatment with amfepramone significantly reduced latency time. 30-day treatment with Tepeex® did not affect motor coordination when compared to the control group. Conclusion: results suggest that homeopathic complex Tepeex® has anxiolytic properties without affecting motor coordination.

Anxiolytic and antidepressive effects of the homeopathic complex Homeo-pax® (pre-clinical study)

Background: The homeopathic complex Homeo-Pax® has been used as an antidepressant and anxiolytic homeopathic medicine available in Brazil. It is a complex mixture prepared with Aconitum nap. 6cH, Aurum met. 6cH, Phosphorus 6cH, Argentum nitricum 6cH, Arsenicum alb. 6cH, and Valeriana officinalis 3cH. Aims: This study had evaluated the behavior in rats after treatment with Homeo-Pax® in pre-clinical models of depression and anxiety. Mathods: Elevated Plus Maze Test (EPM), Forced Swimming Test (FST), Open Field Test (OFT) and the Rota Rod Test (RRT) behavior assays were used to confirm its activity. In the EPM, the animals treated with Homeo-pax® on the 1st day and until the 20th day of treatment remained longer in the open arms of the maze than on 30th day. This result was statistically significant compared with the control group (p < 0.05). In the FST, the treatment with Homeo-pax® (0.5 ml, p.o) increased the swimming time, compared to the control group. This effect was dependent on treatment time, resulting in a similar effect to that presented by amfepramone (10 mg/kg, p.o). In the OFT, crossing by the animals was significantly increased by the treatment with amfepramone (10mg/kg, p.o), and also with the 30-day treatment with Homeo-pax®. In the RRT, the 30-day treatment with Homeo-pax® (0.5 ml, p.o) did not affect the animals’ motor coordination, compared with the control group, which presented the same behavior. Conclusion: Based on the results obtained, it can be suggested that the homeopathic complex Homeo-pax® has anxiolytic and antidepressant properties without affecting motor coordination capacity.

Effects of Terazosin, Silodosin and Alfuzosin on Depression and Anxiety in Mice

Aims: Benign prostatic hyperplasia (BPH) is common urological disease, is characterized by lower urinary tract syndrome, usually associated with sexual dysfunctions. The aim of present study is to investigate the effects of terazosin, silodosin and alfuzosin which are the main treatment options for BPH on depression and anxiety to understand whether these drugs may be effective in BPH caused mood disorders. Study Design: All the drugs were given intraperitoneally (i.p.) in a volume of 0.1 ml per 10 g body weight of mice. Drugs were given 30 min before the experiment. We investigated the effects of terazosin, silodosin and alfuzosin on depression and anxiety, in mice. Place and Duration of Study: Sample: Department of Pharmacology and Department of Urology, Sakarya University, Animal Research Center, between June 2019 and September 2020. Methodology: Here, we examined the effects of terazosin (0.5, 1, 2 mg/kg), silodosin silodosin (1, 3, 10 mg/kg) and alfuzosin (3, 6 and 9 mg/kg) on depression and anxiety by using forced swimming test and elevated plus maze test, respectively, in mice (n:96). Additionally, the locomotor activity was evaluated by open field test. Results: All doses of terazosin, alfuzosin and silodosin significantly increased immobility time, compared to saline group. Silodosin and alfuzosin prolonged the time spent in open arms but terazosin decreased the time spent in open arms compared to saline group. Terazosin, silodosin (1 and 3 mg/kg) and alfuzosin (3 and 6 mg/kg) did not have any effect on the number of entries into the open arms while silodosin (10 mg/kg) and alfuzosin (9 mg/kg) increased the number of entries into open arms. Conclusion: We found that silodosin and alfuzosin had antidepressant and anxiolytic-like effects, while terazosin had depressant and anxiogenic effects. Patients with BPH who need antidepressant and anxiolytic treatment can be treated with a single drug instead of multiple medications.

TO EVALUATE THE EFFECT OF MORUS ALBA LEAVES EXTRACT ON SLEEP AND ANXIETY IN RAT MODELS

Objectives: The objectives of the study were to study the effect of Morus alba leaves extract (MAE) on sleep by phenobarbitone-induced sleeping time and the antianxiety effect by elevated plus maze apparatus model in rats. Methods: In this study, the effect of MAE on sleep was evaluated by the phenobarbitone-induced sleeping time of rats. The onset and the duration of sleep were recorded in minutes. The antianxiety effect was evaluated by the elevated plus maze apparatus model in rats. During 5 min test period, the number of entries into the open arm and closed arm and time spent in the open arm and closed arm were recorded in seconds. Results: MAE at the dose 200 and 400 mg/kg, highly significantly (p<0.001) decreased the onset of phenobarbitone-induced sleeping time. The duration of sleeping time was increased significantly (p<0.01) for 200 mg/kg and highly significantly (p<0.001) for 400 mg/kg as compared to the control group. M. alba has significant antianxiety activity in comparison with control in a dose-dependent manner. M. alba in a dose of 200 mg showed significant (p<0.01) and 400 mg/kg treated groups showed highly significant (p<0.001) anxiolytic activity by increasing the mean time spent in open arms as compared to control but less significant with standard (diazepam). Conclusion: Results indicate that the MAE has a significant dose-dependent effect on phenobarbitone- induced sleeping time and antianxiety effect in the elevated plus maze test.

Oxycodone decreases anxiety-like behavior in the elevated plus-maze test in male and female rats

The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those without one. Therefore, oxycodone might be misused for its anxiolytic properties. We investigated if oxycodone affects anxiety-like behavior in adult male and female rats. The rats were treated with oxycodone (0.178, 0.32, 0.56, or 1 mg/kg), and anxiety-like behavior was investigated in the elevated plus-maze test. Immediately after the elevated plus-maze test, a small open field test was conducted to determine the effects of oxycodone on locomotor activity. In the elevated plus-maze test, oxycodone increased the percentage of time spent on the open arms, the percentage of open arm entries, time on the open arms, open arm entries, and the distance traveled. The males treated with vehicle had a lower percentage of open arm entries than the females treated with vehicle, and oxycodone treatment led to a greater increase in the percentage of open arm entries in the males than females. Furthermore, the females spent more time on the open arms, made more open arm entries, spent less time in the closed arms, and traveled a greater distance than the males. In the small open field test, treatment with oxycodone did not affect locomotor activity or rearing. Sex differences were observed; the females traveled a greater distance and displayed more rearing than the males. In conclusion, oxycodone decreases anxiety-like behavior in rats, and oxycodone has a greater anxiolytic-like effect in males than females.

Behavioral parameters evaluation after homeopathic Zincum metallicum treatment: a transgenerational study in mice

Background: ZINCUM METALLICUM (ZM) is a homeopathic medicine whose materia medica is defined by diverse behavioral and mental symptoms, including depression. Moreover, as a microelement, zinc itself is involved in several functions of Central Nervous System, including development and cell maturity during the intra-uterus life. Aims: Herein, the putative transgenerational effects of different homeopathic potencies of ZM upon behavioral parameters in P and F1 generations were evaluated. Methodology: Since mice and the tail suspension test (TST) are references for evaluating antidepressant agent activity, the TST together with the open field test (OPT) and the elevated plus maze test (EPM) were used to analyze offspring behavioral parameters. All animal procedures were in agreement with the Brazilian ethical research practices and were approved by the institutional ethical committee (CEUA-UNIP) under the protocol 156/2013. Four groups of seven females Balb/C mice were exposed to 0,1mL of ZM 5cH, 30cH, 200cH and lactose 5cH, diluted in 250mL of drinking water, during pregnancy and post partum period, in a total of 31 days. The flasks were coded before the remedies administration and all experimental procedures, including statistical analysis were done in blind. The parents were previously distributed in a Completely Randomized Design for the mates, according to the TST previous results. Mothers were re-evaluated for TST after weaning and mice of F1 generation were evaluated for TST, EPM and OPT when they reached two months old. According to the time of immobilization in TST, animals were classified as healthy (h), intermediate (i) and depressed (d) (< 116; 117-180 and >180 seconds of immobilization, respectively). Results: No significant changes were seen among the groups regarding to the number of newborns, sex proportions, TST, OPT and EPM behavioral parameters, besides the fact that the treatment with ZM 200cH was associated to the majority of healthy F1 mice (male: n=8: 7h+1i+0d; female: n=8: 8h+0i+0d), in relation to the number of delivery per group (Fisher test, p ≤ 0.01). Treatment with ZM 5cH, instead, produced reduced number of pups with no male mouse among F1 generation. We conclude that the treatment of pregnant females with ZM 200cH produced the best results in F1 generation regarding reproduction and behavioral parameters and the treatment with ZM 5cH reduced births in relation to control. The involved mechanisms have to be elucidated in the next steps of the study.

The Role of Melatonin on Behavioral Changes and Concomitant Oxidative Stress in icvAβ1-42 Rat Model with Pinealectomy

One of the pathological hallmarks of Alzheimer’s disease (AD) associated with its progression that contributes to β-amyloid (Aβ) generation is oxidative stress (OS). Clinical data suggest that melatonin is a potent antioxidant that might be effective in the adjunctive therapy of this neurodegenerative disease. The present study aimed to explore the role of melatonin on behavioral changes and markers of OS in three rat models, namely, pinealectomy (pin) model of melatonin deficit, intracerebroventricular (icv)Aβ1-42 model of AD, and combination of both pin and Aβ1-42 model (pin+icvAβ1-42). The chronic injection with vehicle/melatonin (50 mg/kg, i.p. for 40 days) started on the same day of sham/pin and icv vehicle/Aβ1-42 infusion procedures. Anxiety in the open field and the elevated plus-maze test and cognitive responses in the object recognition test were tested between the 30th–35th day after the surgical procedures. Markers of OS in the frontal cortex (FC) and hippocampus were detected by the ELISA method. Melatonin treatment corrected the exacerbated anxiety response only in the pin+icvAβ1-42 model while it alleviated the cognitive impairment in the three models. Pinealectomy disturbed the antioxidant system via enhanced SOD activity and decreased GSH levels both in the FC and hippocampus. The Aβ1-42 model decreased the SOD activity in the FC and elevated the MDA level in the two brain structures. The pin+icvAβ1-42 model impaired the antioxidant system and elevated lipid peroxidation. Melatonin supplementation restored only the elevated MDA level of icvAβ1-42 and pin+icvAβ1-42 model in the hippocampus. In conclusion, our study reveals that the pin+icvAβ1-42 rat model triggers more pronounced anxiety and alterations in markers of OS that may be associated with melatonin deficit concomitant to icvAβ1-42-induced AD pathology.

NEUROPHARMACOLOGICAL SCREENING, ANTI-STRESS ACTIVITY, AND TOXICITY STUDIES OF STANDARDIZED EXTRACT OF THE SEEDS OF CELASTRUS PANICULATUS WILLD

Objective: Celastrus paniculatus Willd, family Celastraceae is an important medicinal plant distributed all over India. Due to the presence of antioxidative polyphenols in C. paniculatus Willd have received much attention for health-promoting properties by scavenging the free radicals, the purpose of this study is to understand neuropharmacological, anti-stress activity, and toxicity studies of standardized seeds extract of “C. paniculatus Willd. Methods: The sun dried C. paniculatus Willd seeds were collected and extracted with ethanol by maceration. Then, the ethanolic extract was subjected to phytochemical screening. The acute toxicity of the ethanolic extract of C. paniculatus was observed as per the Organization for Economic Co-operation and Development guideline no. 423. Neuropharmacological and anti-stress effects were analyzed and evaluated by using physical stress models such as Swimming endurance test, Anoxic tolerance test, Tail suspension test (TST), and Elevated plus maze test. For this study, Swiss albino mice (20–30 g) were divided into five groups of six animals each. Distilled water administered as vehicle in control group and standard group received Withania somnifera (100 mg/kg) while C. paniculatus Willd ethanolic extract (100, 200, and 400 mg/kg) was given orally for 7 days. Results and Discussion: Change in immobility time in swim endurance, first clonic convulsion produced in anoxic tolerance test, immobility time in TST and open arms entry in elevated plus maze test was recorded as parameters. The ethanolic extracts of C. paniculatus Willd significantly reduces the immobility timing along with increases the swimming endurance time, and clonic convulsion timing in anoxic tolerance test in comparison of control group. In tail suspension significant decrease in immobility time and increased open arm entry in elevated plus maze were observed as compare to control group. Conclusion: C. paniculatus Willd has potential as a medicinal plant and it showed protective effect for the stress prevention as the alkaloids are present as main constituents.