Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behavior. Moreover, only a few studies investigated the effect of CBD in female rodents. Therefore, we aimed to (i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects and (ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect 1 h post injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at 1 h and decreasing it at 2 h. In conclusion, strain, sex, and administration time affect CBD’s behavioral response to rodents exposed to tests predictive of antidepressant effects.

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.

ANTI-PARKINSONIAN ACTIVITY OF VARIOUS SOLVENT EXTRACTS OF CLEOME GYNANDRA LEAVES AGAINST MPTP AND ISOLATION OF PHYTOCONSTITUENTS

Antiparkinsonian activity of Cleome gynandra (CG) was evaluated and chemical constituents were isolated. The results of the present study showed that spontaneous motor activity, retention time and number of head drippings were decreased, whereas immobility time in Tail suspension (TST) and Forced swimming test (FST) were increased in MPTP treated animals, while they were significantly (P<0.001) increased and (P<0.01) decreased with various extracts of CG. Dopamine, serotonin (P<0.001), epinephrine (P<0.01) and glutathione levels were significantly decreased and lipid peroxidation was increased in MPTP treated groups, while their levels were significantly (P<0.001) increased and decreased with various extracts of CG in a dose dependant manner as compared to MPTP, L-dopamine and control groups. Ethanolic leaf extract of CG leads to isolation of triterpenoid, flavone and anthocyanidin - O- methylated flavonoids, which were characterized by using spectroscopic investigation methods like FTIR, NMR and MS.

WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity

Cardiac muscle is extremely sensitive to changes in loading conditions; the microgravity during space flight can cause cardiac remodeling and function decline. At present, the mechanism of microgravity-induced cardiac remodeling remains to be revealed. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is an important activator of pressure overload-induced cardiac remodeling by stabilizing disheveled segment polarity proteins 2 (DVL2) and activating the calcium-calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 4 (HDAC4)/myocyte-specific enhancer factor 2C (MEF2C) axis. However, the role of WWP1 in cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether WWP1 was also involved in the regulation of cardiac remodeling caused by microgravity. Firstly, we detected the expression of WWP1 and DVL2 in the heart from mice and monkeys after simulated microgravity using western blotting and immunohistochemistry. Secondly, WWP1 knockout (KO) and wild-type (WT) mice were subjected to tail suspension (TS) to simulate microgravity effect. We assessed the cardiac remodeling in morphology and function through a histological analysis and echocardiography. Finally, we detected the phosphorylation levels of CaMKII and HDAC4 in the hearts from WT and WWP1 KO mice after TS. The results revealed the increased expression of WWP1 and DVL2 in the hearts both from mice and monkeys after simulated microgravity. WWP1 deficiency alleviated simulated microgravity-induced cardiac atrophy and function decline. The histological analysis demonstrated WWP1 KO inhibited the decreases in the size of individual cardiomyocytes of mice after tail suspension. WWP1 KO can inhibit the activation of the DVL2/CaMKII/HDAC4 pathway in the hearts of mice induced by simulated microgravity. These results demonstrated WWP1 as a potential therapeutic target for cardiac remodeling and function decline induced by simulated microgravity.

Study of Antidepressant Activity of Garcinia indica(Kokum) Fruit Rind in Wistar Albino Rats

BACKGROUND Depression is a mental disorder which is treatable but detected less often in primary healthcare settings. Therefore, there is a need for an effective treatment strategy for the management of depression. Garcinia indica (Thouars) Choisy is a slender evergreen tree. An invitro animal study has shown that its phytochemical constituent, hydroxy citric acid has the ability to increase serotonin levels in the brain. Hence, the objective of the study was to evaluate the antidepressant activity of ethanolic extract of Garcinia indica fruit rind in animal models of depression and compare it with control and standard drugs, imipramine, and fluoxetine. METHODS The study was conducted on Wistar albino rats of either sex. The animals were grouped into five, containing six animals in each group. Control (0.1 % carboxymethylcellulose, 10ml/kg), ethanolic extract of Garcinia indica (GIEE1) – 250mg/kg, ethanolic extract of Garcinia indica (GIEE2) – 500mg/kg, Standard1 - Imipramine – 10mg/kg ( Forced Swim test only) and Standard2 - Fluoxetine – 20mg/kg (Tail suspension test only). Drugs were administered for 14 days and antidepressant activity was evaluated on the 14th day after one hour of drug administration using two models - Forced swim test and tail suspension test. Results were tabulated as mean ± SEM (standard error of mean). One-way analysis of variance (ANOVA) followed by Tukey Kramer test was used to interpret the statistical significance. RESULTS The period of immobility was obtained as 21.83 ± 1.44 and14.66 ± 2.74 in forced swim test and 36.8 ± 1.01 and 14.3 ± 0.954 in tail suspension test in GIEE1 and GIEE2 treated groups respectively, which was significantly less compared to control. CONCLUSIONS Garcinia indica has significant antidepressant activity compared to the control. KEY WORDS Antidepressant, Garcinia indica, Fruit Rind, Wistar Albino Rats

Structural characteristics of the bone surrounding dental implants placed into the tail-suspended mice

Background There are many unclear points regarding local structural characteristics of the bone surrounding the implant reflecting the mechanical environment. Purpose The purpose of this study is to quantitatively evaluate bone quality surrounding implants placed into the femurs of mice in an unloading model, and to determine the influence of the mechanical environment on bone quality. Methods Twenty 12-week-old male C57BL6/NcL mice (n = 5/group) were used as experimental animals. The mice were divided into two groups: the experimental group (n = 10) which were reared by tail suspension, and the control group (n = 10) which were reared normally. An implant was placed into the femur of a tail-suspended mouse, and after the healing period, they were sacrificed and the femur was removed. After micro-CT imaging, Villanueva osteochrome bone stain was performed. It was embedded in unsaturated polyester resin. The polymerized block was sliced passing through the center of the implant body. Next, 100-μm-thick polished specimens were prepared with water-resistant abrasive paper. In addition to histological observation, morphometric evaluation of cancellous bone was performed, and the anisotropy of collagen fibers and biological apatite (BAp) crystals was analyzed. Results As a result, the femoral cortical bone thickness and new peri-implant bone mass showed low values in the tail suspension group. The uniaxial preferential orientation of BAp c-axis in the femoral long axis direction in the non-implant groups, but biaxial preferential orientation of BAp c-axis along the long axis of implant and femoral long axis direction were confirmed in new bone reconstructed by implant placement. Collagen fiber running anisotropy and orientation of BAp c-axis in the bone surrounding the implant were not significantly different due to tail suspension. Conclusions From the above results, it was clarified that bone formation occurs surrounding the implant even under extremely low load conditions, and bone microstructure and bone quality adapted to the new mechanical environment are acquired.

Alpha-terpineol: evaluation and pharmacological screening as an antidepressant agent

Objective: To evaluate the possible antidepressant effects of alpha-terpineol in rodents. Material and Methods: Depression levels were analyzed by comparing the total immobility time presented by the animals of the experimental groups in the test session, using the Forced Swimming Test and the Tail Suspension Test. The parameters of locomotion (central, peripheral and total) and motor coordination were evaluated in the Open Field Test and in the Rota Rod Test, respectively. In the second stage, the involvement of the noradrenergic system in the antidepressant action of alpha-terpineol in Forced Swimming Test was investigated. Results and Discussion: After performing the experimental tests, it was observed that the animals that received alpha-terpineol had reduced immobility time in Forced Swimming Test and Tail Suspension Test, compared to the other groups. In the Open Field Test and Rota-rod, the mice showed, respectively, good exploratory activity and motor coordination during the tests. In addition, the study of the Noradrenergic System proved to be a promising mechanism used during its antidepressant action. Conclusion: In view of the results of the experimental tests, alpha-terpineol presented similar responses to those found in other monoterpenes investigated in the literature. Thus, it is shown as a promising antidepressant to be used clinically in humans, with less side effects and low production cost.

Gender, Depression and Zincum metallicum

Background: Depression is a hot topic for research including for the homeopathy community. Laboratory models for human diseases offer the possibility to evaluate depression-like behavior in mice by the tail suspension test (TST), such as the challenge of mothers with induced inflammation by lipopolysaccharide (LPS) during gestation. Moreover, it is known that gender influences depression prevalence and treatment evolution as well in a homeopathic approach. Aims: Verify if the treatment of LPS-challenged pregnant mice with homeopathic Zincum metallicum would change the depression-like behavior of the offspring according to the gender. Methodology: the procedures with animals were previously approved according to local and international law (CEUA-UNIP protocol 156-13). Pregnant randomized BALB/c mice were treated in blind with Zincum metallicum 200c, 30c, 5c and Lactose 5c as control. The treatment lasted 31 days: 21 days from the mating day to the delivery plus ten days of lactating. At the 9.5 days of pregnancy, mothers were challenged or not with 100 microgram/Kg of LPS IP. The pups were separated by sex and mother treatment. The tail suspension test was performed to all pups after they grow up to adulthood (2 months old). Results: The treatment influenced the TST according to gender, but not according to mother’s LPS exposition. Female mice born from mothers treated with 200c potency showed reduction in the immobility time in relation to the control (p-value