Head Dips Research Articles

Behavioural activities and chemical composition of fresh leaf essential oil of Plectranthus aegyptiacus from Southwest Nigeria in mice

Objectives: This study determined the chemical composition of essential oil obtained from fresh leaf of Plectranthus aegyptiacus, and evaluated it for novelty-induced behavioural (NIB) and determine its mechanism(s) of action in mice. Methods: The oil was hydro-distillated, and analyzed using gas chromatography-mass spectrometry. The effects of the oil (50, 100 and 150 mg/kg; i.p., n=6) on novelty-induced behavioural was assessed using open field test and head dipping on hole board. Probable mechanism(s) were evaluated using antagonists: flumazenil, naloxone and cyproheptadine at 2 mg/kg each, atropine and yohimbine at 5 mg/kg and 1 mg/kg respectively. Key Findings: The LD50 values obtained were 2154 and 490 mg/kg for oral and intraperitoneal routes respectively. The oil (50, 100 and150 mg/kg) significantly (p<0.05, 0.01 and 0.01) inhibited all NIB and head dips. Flumazenil significantly (p<0.05) reversed the effect of the oil on NIB; atropine, naloxone and cyproheptadine significantly (p<0.01, 0.01 and 0.001) potentiated inhibitory effect on NIB respectively, while yohimbine showed no significantly effect. The analyzed oil showed 61 compounds, and the major compounds were carvacrol, germacrene-D, p-cymene and [1,1'-Bicyclopentyl]-2,2'-diol. Conclusions: The study concluded that the oil possessed central nervous system depressant activity, which could be mediated mainly through augmentation of GABAergic neurotransmission, while cholinergic-(muscarinic), adrenergic and serotonergic pathways may be involved.

Effect Neonatal Ketamine Treatment on Exploratory and Anxiety-like Behaviours in Adulthood.

ObjectiveIn this study, we evaluated the effect of neonatal ketamine exposure on anxiety-like and exploratory behaviours in adult the Balb/c and C57BL/6 strains of mice which anxiety responses are different.MethodsKetamine was administered at two different doses single dose (10, 20 mg/kg, 0.1 ml/10 g body weight, intraperitoneally) and repeated doses (10, 20 mg/kg every 240 minutes; thrice times) on the 7th postnatal day to male Balb/c and C57BL/6 mice. In adulthood, open-field (OF) and elevated plus maze (EPM) apparatuses were used to evaluate exploratory and anxiety-like behaviour.ResultsIn the C57BL/6 mice, the 20 mg/kg single dose decreased open-arm time and total-arm entries in EPM and increased time of central latency and decreased distance travelled in OF. Both the 10 and 20 mg/kg repetitive doses increased time of central latency and decreased time spent in the centre, frequency of rearing and centre crossing in OF and decreased open-arm time, total-arm entries, number of open-arm entries in EPM. The 20 mg/kg repetitive dose decreased number of head dipping behaviours in EPM. In the Balb/c mice, both the single and repetitive 10−20 mg/kg doses had no significant effect on anxiety-like and exploratory behaviours.ConclusionThere were no significant differences in anxiety-like and exploratory behaviour in different strains by the single 10 mg/kg dose. However, in the C57BL/6 mice, both the single and repetitive 20 mg/kg doses and the 10 mg/kg repetitive dose increased anxiety-like behaviour and decreased exploratory behaviour in EPM and OF. In conclusion, hereditary factors may be effective on the effect of neonatal ketamine treatment on anxiety-like and exploratory behaviour.

Investigation of Potential Antioxidant, Thrombolytic and Neuropharmacological Activities of Homalomena aromatica Leaves Using Experimental and In Silico Approaches

The leaves of Homalomena aromatica are traditionally used in Bangladesh for the treatment of different chronic ailments. The purpose of this study was to explore in vitro antioxidant, thrombolytic activities, and in vivo neuropharmacological effects of methanolic extract of Homalomena aromatica (MEHA) leaves. Antioxidant activity of MEHA was assessed by a DPPH free radical scavenging assay and total phenolics content, total flavonoids content were also measured. The thrombolytic activity was determined by percentage of clot lysis and neuropharmacological activities by hole board, tail suspension, forced swimming and elevated plus maze tests. The results showed that the IC50 value of the extract against DPPH was 199.51 μg/mL. Quantitative analysis displayed higher contents of phenolics and flavonoids (147.71 mg gallic acid equivalent/g & 66.65 mg quercetin equivalent/g dried extract, respectively). The extract also showed a significant clot lysis (33.31%) activity. In case of anxiolytic activity, the elevate plus maze (EPM) test demonstrated an increase in time spent in open arms, and in case of hole board test, the number of head dipping was also significantly increased (p < 0.05). All the test compared with control (1% Tween in water) and standard (diazepam 1 mg/kg), significant dose (200 & 400 mg/kg) dependent anxiolytic activity was found. In antidepressant activity, there was a significant decrease in period of immobility in both test models (tail suspension and forced swimming) (p < 0.05). Moreover, 13 compounds were identified as bioactive, showed good binding affinities to xanthine oxidoreductase, tissue plasminogen activator receptor, potassium channel receptor, human serotonin receptor targets in molecular docking experiments. Furthermore, ADME/T analysis revealed their drug-likeness, likely pharmacological actions and non-toxic upon consumption. Taken together, our finding support the traditional medicinal use of this plant, which may provide a potential source for future drug discovery.

Role of the reuniens and rhomboid thalamic nuclei in anxiety-like avoidance behavior in the rat.

The nucleus reuniens (RE) and rhomboid (RH) nuclei of the ventral midline thalamus are reciprocally connected with the prefrontal cortex (PFC) and the hippocampus (HF) and serve as key intermediaries between these structures, regulating cognitive and emotional behaviors. Regarding affective behavior, several recent reports have described the involvement of RE/RH in the acquisition and retention of conditioned fear, but little is known regarding their role (RE/RH) in anxiety-like behaviors. We examined the role of RH/RE on avoidance and defensive behaviors in male Long Evans rats using the elevated plus maze (EPM). We found that the reversible suppression of RE/RH with muscimol increased avoidance behavior to the open arms of the plus maze as shown by: (a) significant reductions in open arm entries; (b) reductions in the mean duration of time spent in the open arms; and (c) significant increases in retreats during open arm exploration. This was coupled with decreases in the number of head dips in the maze. Consistent with these behavioral effects, a single exposure of naïve rats to the plus maze produced significant increases in c-fos expression selectively in RE and RH of midline thalamic nuclei. We posit that RE/RH normally acts to optimize adaptive responses to anxiety-eliciting situations, and disruptions of RE/RH produce severe deficits in coping behaviors-or as shown here increases in avoidance/defensive behaviors. In sum, the present results establish a novel role for RE/RH in anxiety-like avoidance behavior. In addition to its role in attention, working memory, and executive control, RE/RH also regulates adaptative responses to not only fear but also to anxiogenic stimuli. As such, dysfunction of RE/RH may contribute to the amalgamation of symptoms common to many mental health disorders including anxiety, depression, schizophrenia, and PTSD.

Antidepressant, anxiolytic, antipyretic, and thrombolytic profiling of methanol extract of the aerial part of Piper nigrum: In vivo, in vitro, and in silico approaches.

Piper nigrum L. also called black pepper is popular for its numerous uses. The present research is designed to investigate the pharmacological potential of methanol extract of Piper nigrum (MEPN). The antidepressant investigation was performed by using both in vivo forced swimming test (FST) and tail suspension test (TST) methods while the anxiolytic research by hole‐board test (HBT) method. Again, the antipyretic analysis was conducted through yeast‐induced pyrexia method, whereas clot lysis activity was employed by the thrombolytic method. Furthermore, in silico studies followed by molecular docking analysis of several secondary metabolites, pass prediction, and ADME/T were evaluated with AutoDock Vina, Discovery Studio 2020, UCSF Chimera software PASS online, and ADME/T online tools. The plant extract demonstrated dose‐dependent potentiality in antidepressant, anxiolytic, antipyretic, and thrombolytic activities. Induction of MEPN produced a significant (p < .5, p < .001) increase of mobility in FST and TST, and increased the head dipping and decreased the latency of time (p < .01, p < .001) in HBT. MEPN 400 (mg/kg; b.w.; p.o.) lowered the rectal temperature of yeast‐induced pyrexia substantially (p < .001). Besides, MEPN produced promising (p < .001) clot lysis activity. In the computational approach, among all the proteins, a docking score was found ranging from −1.0 to −7.90 kcal/mol. Besides, all the compounds were found safe in ADME/T study. The results of our scientific research validate the suitability of this plant as an alternative source of novel therapeutics.

Histological Changes in Adipose Tissue: An Alarm When Methamphetamine Is Targeted for Weight Loss Purposes

BACKGROUNDMethamphetamine (METH) may be administered for weight loss purposes and to understand the METH side-effects more in details, this study aimed at determining the effect of METH on changes in adipose tissue in experimental rats.METHODSForty five male Wistar rats were randomly allocated to three equal groups. Group 1 was experimental receiving METH [0.4 mg/kg, subcutaneously (S/C), 0.6 mL/rat] for 3 weeks, group 2 was the sham group receiving normal saline (0.6 mL/rat, S/C) and the 3rd group was the control receiving distilled water, identically. The elevated plus maze test was used to confirm cognitive impairment and distraction as anxiety and to verify addiction to METH by assessing the percent time spent in open arm (OAT), the percent time spent in closed arm (CAT), the percent time spent in central parts and head dipping over the side of the maze. Adipose tissue was assessed histologically 7, 14 and 21-days after interventions. RESULTSA significant increase in anxiety level, and histologically inflammation, degeneration and necrosis in adipose tissue were visible after METH use. CONCLUSIONMETH use resulted in a significant inflammation and necrosis in adipose tissue denoting to the dangers of METH use, when recreationally targeted for weight loss purposes.

Comparative analysis of rats’ behavior in the «elevated plus maze» after the intranasal administration of single-walled carbon nanotubes in a small dose in subacute experiments of different duration

The unique properties of carbon nanotubes (CNT) (increased strength, flexibility, electrical and thermal conductivity) make them very promising for use in various fields of human activity. But the question of their toxic effects on the body is actively discussed in the literature. There is a lot of body toxicity data of large doses of CNT, but the question of the potential danger of small doses of CNT is a practically unexplored issue. Earlier, we showed that a single intranasal injection of single-walled CNT (SWCNT) in a small dose (4 μg / kg) to rats inhibited the mRNA production of most cytokines in both spleen and brain. At the same time, the expression of the early c-fos gene in the olfactory bulb and the pyriform cortex was increased [Loseva E.V. et al., 2016]. It is known very little about the effect of low doses of SWCNT on animal behavior. The aim of this study was to investigate the effect of a small doses of SWCNT with subacute intranasal administration of different duration on the behavior of rats in the elevated plus-maze (EPM) test, which is used to estimate the anxiety. Male Wistar rats were daily intranasal administrated 100 μl of SWCNT suspensions in physiological saline (PS) in small (5.2 μg / kg, n = 9) dose for 4 (n = 9) or 13 (n = 9) days. Control rats were administrated analogically 100 μl of PS (n = 19). A statistical analysis of indicators of rats' behavior in EPM (5 minutes each) was performed using Kruskal-Wallis one-way analysis of variance, and then using the comparison on the non-parametric criterion of Mann-Whitney for independent features by the program STATISTICA 7.0. It was shown that in the EPM test in rats after 4-fold injection of a small dose of SWCNT, as compared with the control group, there was observed the behavior activation in the center and open arm, what was expressed in frequent and lengthy visits, but with a reduction of the average time of such visits. These animals also had increased the vertical exploratory activity (rears), horizontal exploratory activity (head dips) and motor activity, but the grooming indicators were decreased. After chronic administration of SWCNT in a small dose for 13 days, the direction of some of these changes was maintained, but was expressed to a much lesser degree (only at the level of the tendency in comparison to the control group). So, these rats, compared with the control, more often and longer visited the central site, more often visited open arms and less time were in closed arms. At the same time, the average time of the dark visits was smaller, and the average time of grooming, on the contrary, was longer than in the control. Thus, the intranasal administration of SWCNT in a small dose for 4 days in rats had provoked atypical symptoms of anxiety, which were expressed in an agitated behavior in the EPM, as evidenced by the strong activation of most behavioral reactions. The intranasal administration of SWCNT in a small dose for 13 days also has led to some activation of behavior or atypical anxiety, but it was expressed to a much lesser extent than with the acute injection of SWCNT. There wasn't observed an increasing of agitated behavior or a cumulative negative effect of SWCNT during chronic intranasal injection. We can suggest that nanotubes when administered in a small dose for 4 days can penetrate cells and their organelles, causing damage and death of tissue structures, in particular, when they penetrate into the brain, which leads to agitated behavior. At the same time, with subacute administration of SWCNT in a small dose during 13 days, protective reactions can gradually develop, leading to accelerated utilization of nanotubes, for example, by macrophages and astrocytes, which can absorb them, that leads to a diminution of the activation of behavior. To test this assumption, special morpho-functional studies are required.

Evaluation of pharmacological potentials of the aerial part of Achyranthes aspera L.: in vivo, in vitro and in silico approaches

Achyranthes aspera L. (Prickly Chaff flower) is an imperative Asian herb that has been known for numerous healing powers. The aim of this research is to investigate the pharmacological i.e., antidepressant and anxiolytic properties of the methanol extract of aerial part of A. aspera (MEAA) by in vivo and in silico approaches. Additionally, thrombolytic potential of the crude extract has also been explored. The antidepressant and anxiolytic investigations were performed by force swimming test (FST), tail suspension test (TST), and hole board test (HBT) in mice, whereas clot lysis activity test was conducted using thrombolytic experimental method. Furthermore, in silico studies were appraised with Discovery studio, PyRx, UCSF Chimera whereas, PASS prediction, and ADME/T was implemented using online tools. Treatment with MEAA revealed significant (p < 0.05) reduction of immobility time in FST and TST, increased head dipping and decreased the latency of time in HBT. Besides, MEAA produced significant (p < 0.001) clot lysis activity at a minimum dose. In the computer-aided approach, among all the proteins, the docking score has been revealed ranging from − 2.31 kcal/mol to − 7.4 kcal/mol. Spathulenol, diazepam and hydroquinone showed the best binding affinity and all compounds were found safe in ADME/T study. The outcomes of this research demonstrate that MEAA may provide potential for mitigating depression, anxiety, and coagulation.

Involvement of the ventral, but not dorsal, hippocampus in anxiety-like behaviors in mice exposed to the elevated plus maze: participation of CRF1 receptor and PKA pathway.

The hippocampus is a limbic structure involved in anxiety-like behaviors. We aimed to evaluate the role of the dorsal (DH) and ventral (VH) hippocampus in anxiety-like behaviors in the elevated plus maze (EPM). We inhibited these brain regions using cobalt chloride (CoCl2: 1.0nmol) microinjections. We also investigated the involvement of corticotropin-releasing factor (CRF) action and protein kinase A (PKA) pathway using intra-DH and intra-VH microinjections of the CRF1 receptor antagonist CP376395 (0, 3.0, or 6.0nmol) and the PKA inhibitor H-89 (0, 2.5, or 5.0nmol). The results indicated that intra-VH CoCl2 microinjection increased the percentage of time spent and entries in the open arms. The mice also exhibited fewer stretch attend postures in the protected area and increased percentage of open arm entries. Further, intra-VH injection of 3.0nmol CP376395 increased time spent in the open arms. Intra-DH injection of 6.0nmol CP376395 increased the frequency of unprotected head dipping, whereas intra-VH injection of 6nmol CP376395 increased the frequency of protected head dipping. Intra-VH, but not intra-DH, microinjection of 2.5nmol H-89 increased the percentages of open arm entries and time spent in the open arms. Microinjection of 2.5 and 5.0nmol H-89 reduced the frequency of protected head dipping behavior. This study demonstrated that VH modulates anxiety-like behaviors in EPM. Moreover, CRF and the cAMP/PKA pathway seem to modulate these effects.

Neuropharmacological Characterization of Dioclea altissima Seed Lectin (DAL) in Mice: Evidence of Anxiolytic-like Effect Mediated by Serotonergic, GABAergic Receptors and NO Pathway.

Plant lectins have shown promising biological activities in the central nervous system (CNS). This study evaluated the effect of DAL, a lectin isolated from the seeds of the Dioclea altissima species, having binding affinity to D-glucose or D-mannose residues, on mice behavior. Mice (n=6/group) were treated (i.p.) with DAL (0.25, 0.5 or 1 mg/kg) or vehicle and subjected to several tests (open field/OFT, marble-burying/MBT, hole-board/HBT, elevated plus maze/PMT, tail suspension/ TST, forced swimming/FST or rotarod/RRT). Pizotifen, cyproheptadine, flumazenil, L-NAME, 7-NI, Larginine or yohimbine were administered 15 min before DAL (0.5 mg/kg) and the animals were evaluated on PMT. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. The results showed there were no neurobehavioral changes in the mice at the RRT, FST and locomotion in the OFT. DAL (0.25, 0.5 or 1 mg/kg) increased the behavior of grooming and rearing in the OFT, head dips in the HBT, pedalling in the TST and decreased the number of marbles hidden in the MBT. In the PMT, DAL (0.25, 0.5 and 1 mg/kg) and Diazepam increased the frequency of entries in the open arms and the time of permanence in the open arms without affecting the locomotor activity. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and it prevented by pizotifen, cyproheptadine, flumazenil, L-NAME and 7-NI, but not by L-arginine or yohimbine. DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors and NO pathway.

Vitex peduncularis Boosted Anxiolytic, Antidepressant, and Antioxidant Properties in Albino Mice and In Silico Model

ABSTRACT The anxiolytic, antidepressant, and antioxidant activities of Vitex peduncularis leaf extracts in methanol (MEVP) were studied through the in vivo, in vitro, and in silico models. The leaves were extracted with methanol and subjected to in vivo anxiolytic and antidepressant screening by using hole-board test (HBT) and forced swimming test (FST) in adult albino mice. Antioxidant activity was screened by using DPPH scavenging assay and total phenolic content (TPC). In silico studies followed by molecular docking analysis and Absorption, Distribution, Metabolism, and Excretion (ADME) properties of several secondary metabolites evaluated with Schrodinger V11.1. In HBT, the oral MEVP treatment (200 and 400 mg kg−1, b.w.) showed dose-dependency, while 400 mg kg−1 exhibited mean head dipping compared to the standard drug, diazepam (1 mg kg−1). Whereas in FST, the highest dose decreased the period of immobility. DPPH scavenging assay (IC50 = 83.72 μg mL−1) and TPC analysis (97.27 ± 8.64 mg GAE g−1) supported the antioxidant effects of MEVP. The secondary metabolites showed promising binding affinities toward the potassium channel, 5-HT1B, and glutathione reductase protein targets in molecular docking analysis. ADME analysis revealed drug-likeness by following Lipinski’s rule.

Methanol extract of Spathodea campanulata P. (Beauv.) leaves demonstrate sedative and anxiolytic like actions on swiss albino mice

BackgroundSpathodea campanulata P. Beauv. (Bignoniaceae) is a very common plant in Bangladesh which is locally called “Rudrapalash”. In Nigeria leaves extract of S. campanulata has a reputation of being used as an anticonvulsant. In this connection, the aim of this study was to investigate other neuropharmacological effects like sedative and anxiolytic activities of methanol extract of S. campanulata (MESC) leaves in different mice tests.MethodsTo assay sedative activity mice were subjected to open field and hole-cross test, whereas anxiolytic activity was checked by the elevated-plus maze, light-dark box, and hole-board test. For each test, mice were divided into control group (deionized water, 0.1 ml/mouse, p.o.), standard group (diazepam, 1 mg/kg, i.p) and three test groups (200, 400 and 600 mg/kg MESC, p.o.). The acute toxicity test and phytochemical screening of MESC were performed before the pharmacological study.ResultsThe result demonstrated strong sedative and anxiolytic activity of MESC in a dose-dependent manner. All doses of MESC (200, 400 & 600 mg/kg) reduced the number of (square & hole) crossed by mice in both open field and hole cross tests (p < 0.001). On the other hand, in elevated plus-maze and light-dark box test mice opted to stay more in open arms and light box instead of close arms and dark box (p < 0.001). In hole-board test MESC (200, 400 & 600 mg/kg) elevated the number of head dipping (p < 0.001) dose-dependently. Phytochemical investigation indicated the presence of alkaloid, saponin, glycoside, carbohydrate, flavonoid, and tannin in MESC.ConclusionThe experimental results explicit that S. campanulata leaves possess sedative and anxiolytic activities, hence suggest further chemical investigation to identify specific phytoconstituents responsible for sedative and anxiolytic effects.

Glaucacetalin E and galphimidin B from Galphimia glauca and their anxiolytic activity

Ethnopharmacological relevanceGalphimia glauca is a Mexican medicinal plant used to treat anxiety, fear, phobia and stress as it possesses sedative properties which produce a calming effect. Although some chemical and pharmacological studies have already been carried out on G. glauca, there are still new chemical entities from this plant whose anxiolytic activity should be established. Aim of the studyTo validate the use of G. glauca growing in Cuernavaca, Morelos, as an anti-stress agent, through the purification and structural identification of its extracts’ chemical constituents; the analysis of the biogenetic relationship of its chemical compounds, and its biological evaluation to demonstrate its traditional use as anxiolytic agents. Materials and methodsThe structures of all isolated compounds were established based on their spectroscopic and spectrometric data. The structure of compound 2 was corroborated through X-Ray. The anxiolytic and sedative-like activities were assessed by the open-field, hole-board and exploration cylinder test. ResultsThe nor-triterpenes glaucacetalin E (1) and galphimidin B (2) were isolated for the first time along with seven other known compounds, one of them galphimidin (3), from the CHCl3 fraction of the aerial parts of Galphimia glauca. The biogenesis of the natural nor-triterpenes isolated from Galphimia glauca is delineated for the first time starting from the taraxasteryl cation. Oral administration of CHCl3 fraction and 1–3 compounds produced significant attenuation in the anxiety-response in cylinder activity, decrease in the ambulatory activity and in head dipping when compared to the vehicle. However, only the extract enhanced the pentobarbital-induced hypnosis. Diazepam was used as a positive control. ConclusionOur results suggest that G. glauca growing in Cuernavaca, Morelos, exerts anxiolytic-like activity due to the presence of the nor-triterpenes 1–3. These results reinforce the potential use of this species in the treatment of anxiety.

Central nervous system depressant activity of ethanol leaf extract of &lt;I&gt;Globimetula braunii&lt;/I&gt; (Engler) (Loranthaceae) growing on &lt;I&gt;Terminalia catappa&lt;/I&gt; L. (Combretaceae)

This study was carried out to determine phytochemical constituents, median lethal dose (LD50) and central nervous system depressant activity of ethanol leaf extract of Globimetula braunii using laboratory animal models. The intraperitoneal median lethal dose (LD50) of ethanol leaf extract of Globimetula braunii was determined in mice according to the method described by Lorke, 1983. The CNS depressant activity of Globimetula braunii leaf extract was determined using diazepam induced sleep, hole board test and beam walk assay. The ethanol leaf extract of Globimetula braunii revealed the presence of tannins, saponins, steroids, triterpenes, flavonoids and glycoside. The intraperitoneal median lethal dose of the leaf extract of Globimetula braunii was estimated to be 2852 mg/kg bodyweight in mice. The ethanol leaf extract of Globimetula braunii significantly (p &lt;0.05) prolonged the duration of sleep in mice at the dose of 800 mg/kg. The extract prolonged the time to complete the beam walk, and exhibited significant decrease in number of head dips there by indicating a decrease in the exploratory behaviour of the animal. This study suggests that Globimetula braunii possesed sedative property.&#x0D; Keywords: Beam walk assay, diazepam induced sleep, hole board test, central nervous system, Globimetula braunii

Intervention in Neuropsychiatric Disorders by Suppressing Inflammatory and Oxidative Stress Signal and Exploration of In Silico Studies for Potential Lead Compounds from Holigarna caustica (Dennst.) Oken leaves.

Holigarna caustica (Dennst.), a popular plant used in folk medicine in Bangladesh, is often used by the local folk practitioner to treat a variety of chronic diseases. The present research is an attempt to find out an innovative therapeutic prospect for the management of neuropsychiatric disorders. The methanol extract of H. caustica leaves (MEHC) were utilized on various behavioral tests for assessing anxiolytic, anti-depressant, and anti-inflammatory activities. The antioxidant potentials and quantitative phytochemicals were evaluated through spectrophotometric methods. Results revealed that treatment of MEHC (200 and 400 mg/kg) significantly reduced anxiety like behaviors in mice, particularly, 400 mg/kg efficiently improved % of entries and time spent (p < 0.05) in the open arms in elevated plus maze test, whereas, superior head dipping tendency (p < 0.05) was observed in hole-board test. In contrast, mice treated with 200 mg/kg revealed better anxiolytic effect in both open field and hole-cross tests. During antidepressant evaluation, mice administrated with MEHC exhibited active behaviors (swimming and struggling) in forced swimming and tail suspension tests. In parallel, MEHC manifested a noteworthy (p < 0.001) suppression of inflammatory response induced by histamine. The MEHC also showed strong antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (IC50: 57.64 μg/mL) scavenging, H2O2 (IC50: 51.60 μg/mL) scavenging, and ferric reducing power assay. The levels of total phenol, flavonoid, flavonol, condensed tannin, and antioxidant were estimated as higher in MEHC. Moreover, 11 compounds were documented as bioactive, displayed good binding affinities to potassium channel receptor, human serotonin receptor, cyclooxygenase (COX-1 and 2), and xanthine oxidoreductase enzyme targets in molecular docking experiments. Furthermore, ADME/T and Prediction of Activity Spectra for Substances (PASS) analyses exposed their drug-likeness, nontoxic upon consumption, and likely pharmacological actions. Overall, the H. caustica is potentially bioactive as evident by in vivo, in vitro, and computational analysis. Our findings support the folkloric value of this plant, which may provide a potential source towards developing drug leads.

Feed restriction since lactation has reduced anxiety in adult Wistar rats

ABSTRACT Objective To evaluate the effects of macronutrients (protein, carbohydrate and/or lipid) in the diet of young adult (72 days) and adult (182 days) Wistar rats treated ad libitum and with 30% restriction from birth on anxiety in the elevated plus-maze. Methods We used 238 rats treated from birth, composing the groups: Control, Protein, Carbohydrate, Lipid, Carbohydrate and Lipid, Control Restriction, Protein Restriction, Carbohydrate Restriction, Lipid Restriction and Carbohydrate and Lipid Restriction. The animals were weighed at the beginning and at the end of the experiment and tested in the elevated plus-maze. Data were submitted to analysis of variance, followed by the Newman-Keuls Test (p&lt;0.05). Results Among the animals treated ad libitum, the Control, Carbohydrate plus Lipid and Lipid gained more weight than the Carbohydrate and Protein; ad libitum animals gained more weight than those on restriction; among the restrictions, Carbohydrate Restriction rats were the ones that gained less weight. Diet-restricted animals exhibited reduced first-entry latency, greater percentage of entries and time spent, frequency of open arm extremity visits, head dipping (protected and unprotected), and length of stay in the central area of the elevated plus-maze. The animals with 182 days presented greater latency for first entry, reduced frequency of false entries and visits to the ends of the open arms and protected head dipping. Conclusion Food restricted animals, regardless of the macronutrient present in the diet, were less anxious and/or increased their impulsivity and those at 182 days were more anxious and/or with reduced impulsivity.

Effects in rats of adolescent exposure to Cannabis sativa on emotional behavior and adipose tissue.

Cannabis sativa L has remained the most widely used recreational and abused drug worldwide. This study determined adipose tissue histological changes and the anxiety-like behavior in elevated plus-maze tests in rats treated with C. sativa. C. sativa L. was provided from Islamic Azad University Herbarium. To reach cannabis powder, a rotary evaporator was used. Forty-five male Wistar rats were randomly divided into three equal groups of experimental receiving 2 mg/kg of cannabis extract dissolved in 70 % ethanol in 0.6 mL volume subcutaneously daily for three weeks, the sham group subcutaneously injected with equal volume of 70 % ethanol and the control receiving just distilled water, identically. To assess the anxiety level, elevated plus maze was used. Histopathological changes in adipose tissue was evaluated after 7, 14, and 21 days post-intervention. After cannabis administration, inflammation, degeneration and necrosis in adipose tissue occured. Regarding the anxiety level for the percentage of time spent in open arm (OAT), the percentage of time spent in closed arm (CAT), the percentage of time spent in central parts, and head dipping over the side of the maze) after one week, no significant difference was noticed between the groups; but 2 and 3 weeks of cannabis use, the anxiety level significantly increased. Histological findings denoted to inflammation, degeneration and necrosis in adipose tissue after cannabis use. Behavioral assessment of anxiety level revealed that one week after cannabis, no changes were seen in anxiety, but 2 and 3 weeks after cannabis use, the anxiety level increased significantly (Fig. 5, Ref. 38).

Effect of various extracts of Justicia gendarussa leaves on neuropharmacological behavior activity in MPTP induced mice model

The present research work is assessment of various extracts of Justicia gendarussa (JG) leaves on neuropharmacological behavior studies in MPTP induced mice model. Animals were administered with Ethanol, Ethyl acetate, Aqueous and n-hexane extracts at dose 200 and 400mg/kg orally along with MPTP (20mg/kg I.P) 4 injections on day 1 and L-DOPA(100mg/kg I.P) was used as standard. Treatment was continued for 7 days and behavioral assessment was made by spontaneous motor activity, number of head dippings (alertness), rota rod test(grip strength) and immobility time by Tail suspension test (TST) and Forced swimming test(FST) on 1st, 4th and 7th day of treatment. The results of the present study showed that spontaneous motor activity, retention time on rota rod and number of head dipping were decreased (P<0.001) whereas, immobility time in TST and FST were increased (P<0.01) in MPTP induced animals. While the motor scores, alertness and retention time (P<0.001) were increased and immobility time in TST and FST(P<0.01) were decreased significantly and dose dependently with ethanol, ethyl acetate and aqueous extracts on 4th and 7th day of treatment as compared with MPTP, L-dopa and normal control, where as n-hexane extract showed slight activity. Preliminary phytochemical analysis of all the extracts showed presence of flavonoids, poly phenols, amino acids, proteins, terpenoids, carbohydrates, tannins and alkaloids. It was observed that ethanol extract of JG at a dose of 400mg/kg on 7th day exhibited maximum increase in spontaneous motor activity, retention time and number of head dipping and decrease in immobility time in TST and FST as compared to Control, MPTP and L-Dopa treated animals. Evidence of above observations, Justicia gendarussa leaves may be suggested as a potential source for CNS stimulant activity with neuroprotective effect. The effect may be due to presence of L-dopa like compounds, terpenoids, flavonoids -polyphenols (Naringenin), amino acids like tyrosine and proteins.

Neuropharmacological Activity of Various Fractions Obtained from Solanum aethiopicum (Linn.) Fruit in Mice.

Background: Solanum aethiopicum (L.), family Solanaceae, is known as garden eggs. The fruit is used in the treatment of insomnia, diabetes and constipation. Objective: The aim of this study was to evaluate anxiolytic-like activity of fractions obtained from crude methanol extract of Solanum aethiopicum fruit. Method: Acute toxicity testing was conducted according to the OECD guidelines 420 via oral and intraperitoneal routes (ip). n-Hexane (HF), chloroform (CHF), ethyl-acetate (EAF), n-butanol (BF) and residual aqueous fraction (RAF) at doses of 25, 50 and 100 mg/kg ip were experimented using the open field, elevated plus maze, staircase, light dark box and hole-board tests. Results: Results: In open field test, there was statistically significant increase in frequency of central square entry by EAF 25mg/kg, 50mg/kg and 100mg/kg and RAF 25mg/kg, 50mg/kg and 100mg/kg all at p&lt;0.05 compared to distilled water (D/W) group. Elevated plus maze test showed statistically significant increases in open arm entry and duration by CHF 25mg/kg, RAF 25mg/kg and 50mg/kg again at p&lt;0.05. Also, in the staircase test, statistically significant decrease in frequency of rearing with no effect on step climbing was observed by RAF 25mg/kg (p&lt; 0.05) compared to D/W. Light and dark box test produced increased light box entry and duration by EAF 25mg/kg, RAF 25mg/kg and 50mg/ kg at p&lt;0.05. Furthermore, the hole -board test showed statistically significant increases in number of head dips by EAF 50mg/kg and 100mg/kg as well as RAF 25mg/kg, 50mg/kg and 100 mg/kg at p&lt;0.05. Conclusion: The fractions obtained from Solanum aethiopicum fruits possesses anxiolytic-like activity.

Evaluation of Sedative Activity of Methanol Leaf Extract of Ceiba Pentandra Linn (Malvaceae) Using Mice

Background: Insomnia and other associated disorders have been traditionally managed using leaves of Ceiba pentandra (Malvaceae). Methods: In this study, sedative and anxiolytic properties of methanol leaf extract of Ceiba pentandra using mice were evaluated. Acute toxicity study and phytochemical screening of the extract were also determined using standard protocols. The sedative effect of the extract was evaluated using Diazepam and ketamine- induced sleep, hole board test and mouse beam walk assay, whereas the anxiolytic activity was studied using open field, elevated plus maze and elevated stair case tests. Results: The intraperitonial LD50 of the methanol leaf extract of Ceiba pentandra was estimated to be 2150 mg/kg body weight in mice. Preliminary phytochemical screening of the extract revealed the positive reaction of saponins, flavonoids, terpenoids and tannins. The extract at doses of 300 and 600 mg/kg shortened the onset of sleep and prolonged the duration of diazepam-induced sleep. The extract at all doses tested (150,300 and 600 mg/kg) had no effect on mean onset of sleep but significantly (p&lt;0.05) prolonged the duration of ketamine-induced sleep when compared with normal saline treated group. The extract at the doses of 300 and 600 mg/kg significantly (p&lt;0.05) decreased the number of head dips when compared with the control group in the Hole-board test. The extract at all doses tested has no effect on the mean time spent on the beam. However, at the dose of 600 mg/kg, it significantly (p&lt;0.05) increased the number of foot slips made by mice when compared with the control group. In the open field test, the extract at all doses tested (150, 300 and 600 mg/kg) significantly (p&lt;0.05) decreased the number of peripheral square crossing without any effect on the number of centre square crossing. The extract had no effect on the mean number of open arm and closed arm entries, time spent in open arm and time spent in the closed arm. In the elevated staircase test, the extract significantly (p&lt;0.05) reduced the number of stairs climbed and the number of rearing. Conclusion: The results of this work revealed that methanol leaf extract of Ceiba pentandra contains bioactive components that possess sedative properties and hence can be used to treat insomnia in the nearest future.