Anxiolytic Potential Research Articles

Shramahara Mahakasya, a traditional polyherbal formulation, induces anti-anxiety activity in hippocampal neurons by effectuating SOD2-mediated protection against oxidative stress

BackgroundShramahara Mahakasya (SM) is an Ayurvedic polyherbal formulation known for its anti-fatigue and anti-anxiety effects on the human body. However, its mechanism of action remains largely unexplored. In this study, we investigated the intricate mechanisms through which SM polyherbal extract exerts the neuroprotective and anxiolytic effects in cultured HT-22 cells and rodent models. MethodIn this study, the chemical composition of SM was first identified using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The antioxidant potential of SM was evaluated through antioxidant assays such as DPPH, ABTS and FRAP. The neuroprotective activity of SM (200 and 600 μg/mL) was investigated in glutamate (10 mM) assaulted HT-22 cells. The anxiolytic activity of SM (50 and 100 mg/kg) was assessed in a caffeine (50 mg/kg) induced anxiety model of Sprague Dawley rats. The possible underlying mechanisms for the neuroprotective and anxiolytic activities of SM were explored through biochemical assays and brain histology. ResultsOur findings suggest that SM has antioxidant and neuroprotective potential, as evidenced by a decrease in ROS accumulation, Ca2+ overload, mitochondrial membrane potential (MMP) loss, and apoptosis in HT-22 cells subjected to glutamate-induced oxidative stress. The extract also increased SOD2 levels and decreased cleaved caspase-3 levels across various treatment sets. The anxiolytic activity of SM was demonstrated by improved behavior of the animals in the elevated plus maze test and increased SOD activity in the brain. SM exhibited the most effective improvements in anxiety disorder at a dose of 100 mg/kg body weight in rats. ConclusionsThis study is a pioneering investigation depicting the antioxidant, neuroprotective, anti-apoptotic, and anxiolytic potential of SM formulation against glutamate/caffeine-induced oxidative stress and anxiety in both in vitro and in vivo situations. Overall, our study suggests that the regular consumption of SM formulation could effectively prevent anxiety symptoms by reducing oxidative stress in neuronal cells.

Exploring the physiological response differences of β-caryophyllene, linalool and citral inhalation and their anxiolytic potential

Essential oils with β-caryophyllene, citral, and linalool as key compounds often exhibit some anti-anxiety like effects in aromatherapy. However, evidence of the effect of these three compounds through human inhalation remains limited. It is worth exploring their potential anxiolytic effect through the olfactory pathway, and finding out whether the three compounds lead to different physiological responses. A total of 48 subjects were randomly assigned to three odor (β-caryophyllene, citral, and linalool) inhalation groups and one control (odorless jojoba oil) group. Stress stimulation was induced using n-back and mental arithmetic tasks. The odor was administered before the task test session. Assessments including the State-Trait Anxiety Inventory (STAI), electroencephalogram (EEG) activities, facial expressions, several physiological indicators, and a self-report scale of subjective perception of the odor environments were carried out. The changes before and after inhalation, as well as the inter-group differences, were analyzed. Both β-caryophyllene and citral inhalation led to a significant decrease in anxiety levels, while only β-caryophyllene resulted in a notable reduction across both sub-scales of STAI. Following the odor inhalation, heart rate significantly decreased in all three groups, with the β-caryophyllene group exhibiting the most pronounced decline. While the systolic blood pressure of the linalool group demonstrated a statistically significant difference. Regarding facial expressions, β-caryophyllene significantly increased the ratio of 'Happiness' and decreased the ratio of ‘Fear'. In the non-task state, citral reduced the power of frontal alpha, delta, and theta waves while β-caryophyllene had a similar effect. All odor inhalation groups showed increased delta and theta waves after the task compared with the control group, with the β-caryophyllene group having notably lower frontal beta waves. β-Caryophyllene and citral exhibited good anti-anxiety effects. Subjects receiving different odors showed different EEG and physiological responses, indicating the differences in emotional regulation ways among the three compounds.

Potential anxiolytic therapeutics from Hybanthus enneaspermus (L.) F. Muell. - mitigate anxiety by plausibly modulating the GABAA-Cl- channel

Anxiety is a commonly prevailing psychological disorder that requires effective treatment, wherein phytopharmaceuticals and nutraceuticals could offer a desirable therapeutic profile. Hybanthus enneaspermus (L.) F. Muell. is a powerful medicinal herb, reportedly effective against several ailments, including psychological disorders. The current research envisaged evaluating the anxiolytic potential of the ethanolic extract of Hybanthus enneaspermus (EEHE) and its toluene insoluble biofraction (ITHE) employing experimental and computational approaches. Elevated Plus Maze, Light and Dark Transition, Mirror Chamber, Hole board and Open field tests were used as screening models to assess the antianxiety potential of 100, 200 and 400 mg/kg body weight of EEHE and ITHE in rats subjected to social isolation, using Diazepam as standard. The brains of rats exhibiting significant anxiolytic activity were dissected for histopathological and biochemical studies. Antioxidant enzymes like catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase; and neurotransmitters viz. monoamines (serotonin, noradrenaline, dopamine), Gamma-aminobutyric acid (GABA), and glutamate were quantified in the different regions of rats’ brain (cortex, hippocampus, pons, medulla oblongata, cerebellum). Chromatographic techniques were used to isolate phytoconstituents from the fraction exhibiting significant activity that were characterized by spectroscopic methods and subjected to in silico molecular docking. ITHE at 400 mg/kg body weight significantly mitigated anxiety in all the screening models (p < 0.05), reduced the inflammatory vacuoles and necrosis (p < 0.05) and potentiated the antioxidant enzymes (p < 0.05). It enhanced the monoamines and GABA levels while attenuating glutamate levels (p < 0.01) in the brain. Three significant flavonoids viz. Quercitrin, Rutin and Hesperidin were isolated from ITHE. In silico docking studies of these flavonoids revealed that the compounds exhibited substantial binding to the GABAA receptor. ITHE displayed a promising pharmacological profile in combating anxiety and modulating oxidative stress, attributing its therapeutic virtues to the flavonoids present.

Effect of Cinnamaldehyde Chalcone on Behavior in Adult Zebrafish (Danio rerio): In Silico Approach.

The study focuses on the anxiolytic potential of chalcone (2E,4E)-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-one (CHALCNM) in adult zebrafish. Successfully synthesized in 58 % yield, CHALCNM demonstrated no toxicity after 96 h of exposure. In behavioral tests, CHALCNM (40 mg/kg) reduced locomotor activity and promoted less anxious behavior in zebrafish, confirmed by increased permanence in the light zone of the aquarium. Flumazenil reversed its anxiolytic effect, indicating interaction with GABAA receptors. Furthermore, CHALCNM (4 and 20 mg/kg) preserved zebrafish memory in inhibitory avoidance tests. Virtual screening and ADMET profile studies suggest high oral bioavailability, access to the CNS, favored by low topological polarity (TPSA≤75 Å2) and low incidence of hepatotoxicity, standing out as a promising pharmacological agent against the GABAergic system. In molecular coupling, CHALCNM demonstrated superior affinity to diazepam for the GABAA receptor. These results reinforce the therapeutic potential of CHALCNM in the treatment of anxiety, highlighting its possible future clinical application.

An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies

The constant use of alcoholic beverages can deregulate serotonin levels, affecting neurotransmitters and triggering symptoms of anxiety. In this context, the objective of this work was to evaluate the anxiolytic potential and possible action mechanisms of the natural compound amentoflavone against the deleterious effects caused by alcohol withdrawal on the behavior of adult zebrafish (aZF). The experiments showed that amentoflavone did not change locomotion and did not cause toxicity in aZF during up to 96 h of analysis, with a median lethal concentration (LC50) greater than 1.0 mg/mL. The reversal of anxiety by pretreatment with granisetron suggested that the anxiolytic effect of amentoflavone is dependent on serotonergic 5-HT3A/3B receptors. Furthermore, amentoflavone reversed anxiety due to flumazenil pretreatment, suggesting a dependence on the GABAA receptor. The three concentrations of amentoflavone tested were effective in treating anxiety resulting from alcohol withdrawal. In silico analysis validated the in vivo results, supporting the idea that the interaction of amentoflavone with the protein occurs in a more stable manner than reference compounds. Amid growing interest in natural alternatives to treat anxiety disorders, amentoflavone is a potential candidate for a new anxiolytic compound that acts specifically on the 5HT3A/3B and GABAergic serotonergic pathways.

Network pharmacology combined with molecular docking and experimental verification to elucidate the effect of flavan-3-ols and aromatic resin on anxiety

This study investigated the potential anxiolytic properties of flavan-3-ols and aromatic resins through a combined computational and experimental approach. Network pharmacology techniques were utilized to identify potential anxiolytic targets and compounds by analyzing protein–protein interactions and KEGG pathway data. Molecular docking and simulation studies were conducted to evaluate the binding interactions and stability of the identified targets. Behavioral tests, including the elevated plus maze test, open field test, light–dark test, actophotometer, and holeboard test, were used to assess anxiolytic activity. The compound-target network analysis revealed complex interactions involving 306 nodes and 526 edges, with significant interactions observed and an average node degree of 1.94. KEGG pathway analysis highlighted pathways such as neuroactive ligand-receptor interactions, dopaminergic synapses, and serotonergic synapses as being involved in anxiety modulation. Docking studies on EGCG (Epigallocatechin gallate) showed binding energies of −9.5 kcal/mol for MAOA, −9.2 kcal/mol for SLC6A4, and −7.4 kcal/mol for COMT. Molecular dynamic simulations indicated minimal fluctuations, suggesting the formation of stable complexes between small molecules and proteins. Behavioral tests demonstrated a significant reduction in anxiety-like behavior, as evidenced by an increased number of entries into and time spent in the open arm of the elevated plus maze test, light–dark test, open field center activity, hole board head dips, and actophotometer beam interruptions (p < 0.05 or p < 0.01). This research provides a comprehensive understanding of the multi-component, multi-target, and multi-pathway intervention mechanisms of flavan-3-ols and aromatic resins in anxiety treatment. Integrated network and behavioral analyses collectively support the anxiolytic potential of these compounds and offer valuable insights for future research in this area.

Design, synthesis, and evaluation of anxiolytic activity of 2-(4-phenylpiperazin-1-yl)-1H-benz[d]imidazole and 2-(4-phenylpiperazin-1-methyl)-1H-benz[d]imidazole derivatives

BackgroundIn contemporary society, anxiety has become a widespread disorder leading to compromised well-being and heightened depressive states. Extensive literature reviews indicate the diverse biological effects of benzimidazole and piperazine derivatives, notably their impact on the central nervous system. This study aimed to design, molecularly dock, synthesize, and assess the anxiolytic potential of six derivatives of 2-(4-phenylpiperazin-1-yl)-1H-benz[d]imidazole and 2-(4-phenylpiperazin-1-methyl)-1H-benz[d]imidazole.ResultsIn the present study, an attempt was made to synthesize benzimidazole derivatives conventionally. The benzimidazole nuclei are condensed with various substituted piperazines to obtain targeted benzimidazole–piperazine hybrids. Their anxiolytic activity is determined using the Elevated Plus Maze test and hole board test in mice. All compounds have shown good docking scores and in vivo anxiolytic activity.ConclusionOut of all the derivatives synthesized, compounds 5b, 5c, and 5f exhibited outstanding anxiolytic efficacy in both computational simulations and live subjects. Compound 5b demonstrated a remarkable docking score relative to the ligand, suggesting its potential as a promising candidate warranting further exploration.

Antidepressant and anxiolytic potential of Citrus reticulata Blanco essential oil: a network pharmacology and animal model study.

Citrus reticulata Blanco essential oil (CBEO) has attracted increasing attention as a potential treatment for depression and anxiety in recent years. However, there is limited evidence regarding the active compounds responsible for its therapeutic effects. In addition, substantial amounts of CBEO and prolonged therapy are often required. This study aims to investigate the rapid acting antidepressant and anxiolytic effects of CBEO, identify the underlying composition as well as optimize its dosage and duration. CBEO composition was determined using gas chromatography-mass spectrometry (GC-MS), and the corresponding targets were obtained from the SwissTargetPrediction database. Depression-related targets were collected from DisGeNET, GeneCards, Therapeutic Target Database, and Online Mendelian Inheritance in Man. Subsequently, the overlap between CBEO and depression targets was utilized to build a network diagram depicting the relationship between the active ingredients and targets using Cytoscape software. The STRING database facilitated the construction of a protein-protein interaction network, and the Ma'ayan Laboratory Enrichment tool was employed for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Wiki pathway analyses. Molecular docking was conducted using AutoDock Vina and Discovery Studio Visualizer. Topological analysis predicted the main antidepressant active ingredients in CBEO. A mixture of these compounds was prepared based on their relative GC-MS ratios. Tail suspension test, elevated plus maze, corticosterone-induced PC12 cells, and lipopolysaccharide (LPS)-induced BV2 cells were used to validate the antidepressant and anxiolytic potential of CBEO and CBEO's main bioactive constituents. CBEO contains 18 components that target 121 proteins. We identified 595 targets associated with depression; among them, 29 targets were located between essential oils and depression. Topological results revealed that linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol were the major active compounds of CBEO in the management of depression. GO analysis identified G protein-coupled opioid receptor activity, phospholipase C-activating G protein-coupled receptor, and neuron projections that were mostly related to molecular functions, cellular components, and biological processes. Neuroactive ligand-receptor interactions, chemical carcinogenesis, and calcium signaling pathways were the major pathways identified in KEGG analysis. Molecular docking showed that the main bioactive ingredients of CBEO had favorable binding affinities for Protein-Protein Interaction's hub proteins, including OPRM1, PTGS2, ESR1, SLC6A4, DRD2, and NR3C1. These five compounds were then mixed at 0.8:5:0.6:2:1 (w/w) ratio to form a CBEO antidepressant active compound mixture. An acute intranasal treatment of CBEO (25mg/kg) only demonstrated an antidepressant effect, whereas the main bioactive compounds combination (12.5mg/kg) illustrated both antidepressant and anxiolytic effects in mice. Linalool, p-cymene, and terpinene-4-ol exhibited neuroprotective and anti-neuroinflammation in the in vitro study, while these effects were not observed for α-terpinene and α-terpineol. Linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol cymene might be mainly contributing to CBEO's antidepressant effect by regulating neuroactive ligand-receptor interaction, neuron projection, and receptor signaling pathway. A mixture of these compounds showed rapid antidepressant potential via intranasal administration, which was comparable to that of CBEO. The mixture also exhibited an anxiolytic effect while not seen in CBEO.

An investigation on the role of oxytocin in chronic neuropathic pain in a Wistar rat model

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect with ineffective preventative and curative treatment. Currently, only Duloxetine has been recommended as effective treatment for CIPN, which has shown individual-dependent, short-term analgesic effects, with limiting adverse effects and poor bioavailability. The neuropeptide, oxytocin, may offer significant analgesic and anxiolytic potential, as it exerts central and peripheral attenuating effects on nociception. However, it is unknown whether the intervention administered in a model of CIPN is an effective therapeutic alternative or adjuvant. Materials and Methods The intervention was divided into two phases. Phase 1 aimed to induce CIPN in adult Wistar rats using the chemotherapeutic agent Paclitaxel. Mechanical (electronic von Frey filament) and thermal (acetone evaporation test and Hargreaves test) hypersensitivity testing were used to evaluate changes due to the neuropathic induction. Phase 2 consisted of a 14-day intervention period with saline (o.g.), duloextine (o.g.), or oxytocin (i.n.) administered as treatment. Following the intervention, anxiety-like behaviour was assessed using the elevated plus maze (EPM) and light–dark box protocols. Analysis of peripheral plasma corticosterone, peripheral plasma oxytocin, and hypothalamic oxytocin concentrations were assessed using ELISA assays. Results The findings showed that we were able to successfully establish a model of chemotherapy-induced peripheral neuropathy during Phase 1, determined by the increase in mechanical and thermal nociceptive responses following Paclitaxel administration. Furthermore, the animals treated with oxytocin displayed a significant improvement in mechanical sensitivity over the intervention phase, indicative of an improvement in nociceptive sensitivity in the presence of neuropathic pain. Animals that received Paclitaxel and treated with oxytocin also displayed significantly greater explorative behaviour during the EPM, indicative of a reduced presence of anxiety-like behaviour. Conclusion Our results support the hypothesis that intranasally administered oxytocin may augment the analgesic and anxiolytic effects of duloxetine in a chemotherapy induced peripheral neuropathy model in a Wistar rat. Future studies should consider administering the treatments in combination to observe the potential synergistic effects.

Molecular Docking and GC/MS-Based Approach for Identification of Anxiolytic Alkaloids from Griffinia (Amaryllidaceae) Species in a Zebrafish Model.

Griffinia gardneriana Ravenna, Griffinia liboniana Morren and Griffinia nocturna Ravenna (Amarillydaceae) are bulbous plants found in tropical regions of Brazil. Our work aimed to determine the alkaloid profiles of Griffinia spp. and evaluate their anxiolytic potential through in vivo and in silico assays. The plants grown in greenhouses were dried and their ground bulbs were subjected to liquid-liquid partitions, resulting in alkaloid fractions that were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Anxiolytic activity was evaluated in zebrafish (Danio rerio) through intraperitoneal injection at doses of 40, 100 and 200 mg/kg in light-dark box test. GC-MS analyses revealed 23 alkaloids belonging to different skeleton types: lycorine, homolychorine, galanthamine, crinine, haemanthamine, montanine and narcisclasine. The chemical profiles were relatively similar, presenting 8 alkaloids common to the three species. The major component for G. gardneriana and G. liboniana was lycorine, while G. nocturna consisted mainly of anhydrolycorine. All three alkaloid fractions demonstrated anxiolytic effect. Furthermore, pre-treatment with diazepam and pizotifen drugs was able to reverse the anxiolytic action, indicating involving the GABAergic and serotonergic receptors. Molecular docking showed that the compounds vittatine, lycorine and 11,12-dehydro-2-methoxyassoanine had high affinity with both receptors, suggesting them to be responsible for the anxiolytic effect.

The Anxiolytic Potential of Citrus Aurantium Essential Oil: A focused critical review

Anxiety disorders rank among the most common mental health issues globally, prompting extensive research into both traditional and alternative treatments. In this context, Citrus aurantium essential oil (bitter orange) has attracted scientific interest due to its anxiolytic properties. This essential oil's pharmacological effects are attributed to its active components, which interact with key neurotransmitter systems, including the serotoninergic and GABAergic, to exert anxiolytic, antidepressant, and sedative effects. Recent studies have explored these properties in various models, demonstrating Citrus aurantium's ability to alleviate anxiety-like behaviors in animal models and manage preoperative anxiety in humans. Despite promising preliminary findings, research on Citrus aurantium essential oil's efficacy and safety in anxiety treatment presents considerable variability in study design, methodologies, and outcomes. This review aims to synthesize current evidence on the anxiolytic effects of Citrus aurantium essential oil, highlighting its potential therapeutic applications and the need for further research to clarify its efficacy and safety in clinical settings. By critically evaluating existing literature, this paper contributes to a deeper understanding of Citrus aurantium essential oil as a potential non-pharmacological intervention for anxiety disorders, underscoring the importance of continued investigation in this promising area of complementary and alternative medicine.

Development and evaluation of anxiolytic potential of bagels incorporated with banana peel flour and lavender

Anxiety affects a quarter of people globally. It can be treated with medicinal plants i.e., Lavendula angustifolia, with anxiolytic compounds, and fruits such as banana, with mood-stabilizing vitamins and minerals. Functional baking products are being designed to address prevalent nutritional issues. Bagels are bakery products made by cold fermentation. Therefore, the present study was designed to make therapeutic bagels by incorporating lavender and banana peel powder to evaluate the anxiolytic effect. Whole wheat was used to prepare the control treatment. The combination of whole wheat flour and banana peel powder (90:10) was used to make subsequent three treatments with lavender (T0: 0 ml, T1: 5 ml, T2: 10 ml, and T3: 15 ml). Sensory evaluation declared T2 as the most acceptable one. Thus, it was selected for a daily intervention lasting 2–3 weeks. There was a significant (p < 0.01) reduction in the anxiety score of experimental subjects. The final product was analyzed for proximate (moisture, protein, fat, and fiber), physical (color and texture), and phytochemical analysis (antioxidant and total phenolics). The moisture, protein, and fiber content increased from T0 to T1 but remained constant in T1, T2, and T3. While fats, DPPH, and TPC increased significantly (p < 0.01) from T0 to T3 as 5.25 ± 0.10 to 7.21 ± 0.09, 18.09 ± 0.26 to 47.84 ± 0.27, and 21.53 ± 0.17 to 1.58 ± 0.19, respectively. Banana peel powder imparted a darker tone in bagels. Hence, they can be utilized in value-added food products to relieve stress and anxiety. In future, bioactive characterization of the product and efficacy studies can be done.

Benzodiazepine derivatives for the treatment of neuropharmacological disorders and pain management: Docking investigations and in-vivo studies

Benzodiazepines are well-known for their medicinal properties. The current study aimed to evaluate and seek new therapeutic possibilities of some of these compounds for addressing anxiety and pain. Four benzodiazepine derivatives were synthesized, characterized, and subjected to computational assessment of the GABAergic response upon interaction with human GABA-A receptors (PDBID: 6×3x) relative to the drug diazepam (DZP) to achieve the objective. Apart from the docking analysis, ADME analysis of the compounds was also performed. Following the in-silico evaluations, two of the synthesized compounds (designated as P3 and P4) were identified for subsequent in-vivo investigations utilizing laboratory rats to explore their anxiolytic potential in comparison to diazepam, and their analgesic efficacy relative to diclofenac sodium. The combination of in-silico and in-vivo assessments uncovered the binding sites of P4 (a fluoro derivative) and its potential as a superior anxiolytic drug compared to P3 (a hydroxy derivative) for analgesic relief. The ADME pharmacokinetic evaluation of the synthesized compounds by Lipinski rule of 5 suggested the oral bioavailability of these drugs. These findings are important as they provide valuable insights into the potential development of new anxiolytic and analgesic agents from the benzodiazepine derivatives that can be easily synthesized and developed into affordable drugs.

Investigating anxiolytic effect of intranasal micro emulsion in experimental animal models

This investigation aimed to assess the anxiolytic potential of an intranasal micro emulsion formulation in an experimental model utilizing Swiss Albino Mice. The evaluation of anti-anxiety activity was conducted through the Elevated plus Maze and Open Field tests. In the Elevated plus Maze, parameters such as the total count of arm entries and the duration spent in both open and enclosed arms were meticulously recorded. Similarly, the Open Field tests involved the documentation of entries in the central region, the time spent in the central region, entries into the peripheral zone, and time spent in the peripheral zone. The experimental subjects received treatment with the intranasal micro emulsion formulation at a dosage of 50mg/kg. The results from the Elevated plus Maze exhibited a noteworthy (p&lt;0.01**) augmentation in the quantity of entries and the duration of sojourn within the open arm. Parallelly, the Open Field tests revealed a significant (p&lt;0.01**) escalation in the count of squares traversed and the frequency of crossings. This investigation unequivocally indicated that the intranasal micro emulsion formulation elicited a pronounced anti-anxiety effect in the experimental animal model. This research contributes to the expanding body of knowledge on the potential therapeutic efficacy of intranasal micro emulsion formulations in addressing anxiety-related behaviors, thereby paving the way for further investigations and potential clinical applications.

A comparative study of anti-anxiety properties of ethanolic and aqueous extracts of Ocimum sanctum in animal models

Background: Anxiety transcends a natural emotion, evolving into a pathological condition with the potential to trigger cascading cardiovascular and psychiatric disorders. Although conventional allopathic medicine offers treatment options, concerns regarding their side effects and long-term efficacy remain prevalent. Medicinal plants contain natural compounds that may be promising sources of therapeutic drugs. Aims and Objectives: This study aims to compare the anxiolytic potential of ethanolic and aqueous extracts of Ocimum sanctum (OS). The growing appeal of plant-based therapies for anxiety stems from perceived advantages in safety and tolerability compared to synthetic drugs. Materials and Methods: The anxiolytic activity of aqueous and ethanolic extract of OS is evaluated with an elevated plus maze test. A total of 36 Wistar albino rats (150–200 g) were used and randomly divided into six groups of six animals each. The effects of the test drug at different doses, 100 and 200 mg/kg, were compared with the standard anxiolytic drug diazepam at 2 mg/kg body weight and the control group using distilled water at 0.5 mL/kg body weight. Results: The behavioral changes suggested reduced anxiety and openarm exploration in plus-maze indicates reduced anxiety in animals treated with OS extracts. The changes are significantly (P &lt; 0.001) comparable with the standard drug diazepam. Conclusion: The ethanolic extracts of OS are more significant than aqueous extracts for evaluating anti-anxiety activity in a dose-dependent manner. In addition, ethanolic extracts are more likely to contain a wider range of bioactive compounds, which are thought to be responsible for the anti-anxiety effects of OS.

Synthesis, molecular docking, ADMET, and evaluation of the anxiolytic effect in adult zebrafish of synthetic chalcone (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one: An in vivo and in silico approach.

Anxiety disorders represent the complex interaction between biological, psychological, temperamental, and environmental factors; drugs available to treat anxiety such as benzodiazepines (BZDs) are associated with several unwanted side effects. Although there are useful treatments, there is still a need for more effective anxiolytics with better safety profiles than BZDs. Chalcones or 1,3-diphenyl-2-proper-1-ones can be an alternative since this class of compounds has shown therapeutic potential mainly due to interactions with GABAA receptors and serotonergic system. This study evaluated the anxiolytic potential of chalcone (E)-3-(4-(dimethylamino)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (C2OHPDA) in adult zebrafish (Danio rerio) (ZFa). Each animal (n = 6/group) was treated intraperitoneally (i.p.; 20 μL) with the chalcone (4, 20, and 40 mg/kg) and with the vehicle (DMSO 3%; 20 μL), being submitted to the tests of locomotor activity and 96-h acute toxicity. The light/dark test was also performed, and the serotonergic mechanism (5-HT) was evaluated through the antagonists of the 5-HTR1 , 5-HTR2A/2C , and 5-HTR3A/3B receptors. It was investigated the prediction of the chalcone's position and preferential orientation concerning its receptor, as well as the pharmacokinetic parameters (ADMET) involved in the process after administration. As a result, C2OHPDA was not toxic and reduced the locomotor activity of ZFa. Furthermore, chalcone demonstrated an anxiolytic effect on the central nervous system (CNS), mediated by the serotonergic system, with action on 5-HT2A and 5-HTR3A/3B receptors. The interaction of C2OHPDA with 5-HT2A R and 5-HT3A receptors was confirmed by molecular docking study, the affinity energy observed was -8.7 and -9.1kcal/mol, respectively. Thus, this study adds new evidence and highlights that chalcone can potentially be used to develop compounds with anxiolytic properties.

Anxiolytic potential of resveratrol and rufinamide combination by modulating GABA-ergic transmission: insights from experiments, molecular docking and dynamics simulations.

Resveratrol is a polyphenolic phytocompound known to possess anxiolytic-like effects but its impact on central gammaaminobutyric acid (GABA) modulation has never been explored. The purpose of this study was to analyze the anxiolytic-like effects of resveratrol alone and in combination with rufinamide, an antiepileptic drug which has never been studied for its anxiolytic potential. The BALB/c mice were tested in a battery of behavior testing after administration of resveratrol (50 mg/kg) and rufinamide (50 mg/kg) alone and in combination. Moreover, molecular docking studies were also carried out to understand the interaction of resveratrol and rufinamide with GABA aminotransferase, GABA receptor and GABA-A transporter type 1. Resveratrol alone exerted notable anxiolytic-like effects and improved outcomes in few experiments but rufinamide alone did not yield any beneficial outcomes. However, the animal co-administered with resveratrol and rufinamide behaved exceptionally well (p<0.05) and preferred open, illuminated and exposed areas of open field, light/dark and elevated plus maze. Further, these animals showed reduced anxiety towards anxiogenic stimuli i.e. holes and marbles in hole board and marble bury tests, respectively. Resveratrol and rufinamide showed moderate to strong binding affinities with GABA proteins, indicating the potential to treat anxiety-like neurological disorders. Moreover, resveratrol and rufinamide were analyzed using molecular docking to determine their interaction with GABA receptors, transporters, and transaminase. The results suggest that their anxiolytic-like effects may be due to inhibiting GABA reuptake transporter 1 protein, leading to increased synaptic levels of GABA neurotransmitter, as seen in stable molecular dynamics results with the 7SK2 GABA transporter protein.

Cognitive Enhancement in Mice: a Data Driven Predictive Model for Evaluating Anxiolytic Effects of Diazepam using Supervised Machinelearning Approach

In the discipline of pharmacology, where it is vital to investigate natural substances for therapeutic benefits, this study investigates the topic of cognitive enhancement in mice with a focus on the anxiolytic characteristics of diazepam. We present a novel approach to predict and assess the anxiolytic potential of diazepam by combining pharmacology with supervised machine learning and making use of the power of modern data analysis techniques.Machine learning is frequently used to build mathematical models that explain or predict data driven based on previous observations. The support vector regressor, Linear Regression, and naïve Bayesian classifier are perhaps among the most popular supervised algorithms. Behavioral pharmacology, which assesses the behavior of experimental subjects after being injected with various chemicals to see if they have positive or negative effects, is an area of possible application. Diazepam (0.5 and 2 mg/kg) was tested in the elevated plus maze (EPM) in the current investigation to determine its effects. Machine learning techniques (SVR Algorithm) was applied. The results showed an effective anxiolytic effect of the 2 mg/kg dose of diazepam when compared with the control group. The findings of the research using conventional statistical methods indicate that progesterone, at a dose of 2 mg/kg, has an impact that is similar to anxiolytics. The variables that provide additional information to distinguish the experimental groups are automatically identified via machine learning.

Clove volatile oil-loaded nanoemulsion reduces the anxious-like behavior in adult zebrafish.

Clove volatile oil (CVO) and its major compound, eugenol (EUG), have anxiolytic effects, but their clinical use has been impaired due to their low bioavailability. Thus, their encapsulation in nanosystems can be an alternative to overcome these limitations. This work aims to prepare, characterize and study the anxiolytic potential of CVO loaded-nanoemulsions (CVO-NE) against anxious-like behavior in adult zebrafish (Danio rerio). The CVO-NE was prepared using Agaricus blazei Murill polysaccharides as stabilizing agent. The drug-excipient interactions were performed, as well as colloidal characterization of CVO-NE and empty nanoemulsion (B-NE). The acute toxicity and potential anxiolytic activity of CVO, EUG, CVO-NE and B-NE against adult zebrafish models were determined. CVO, EUG, CVO-NE and B-NE presented low acute toxicity, reduced the locomotor activity and anxious-like behavior of the zebrafish at 4 - 20mgkg-1. CVO-NE reduced the anxious-like behavior of adult zebrafish without affecting their locomotor activity. In addition, it was demonstrated that anxiolytic activity of CVO, EUG and CVO-NE is linked to the involvement of GABAergic pathway. Therefore, this study demonstrates the anxiolytic effect of CVO, in addition to providing a new nanoformulation for its administration.

DOSE DEPENDENT EFFECTS OF TWO POLYMERIC MATERIALS AND SIMILARITIES WITH CERTAIN DRUGS

Polymeric materials became of crucial interest in the research area over the recent years due to worldwide production increase of these materials not always being followed by knowledge of their possible detrimental effects. Therefore, in the present study we analyzed the different effects of polymeric materials at various exposure times. Our results focused on some general effects in terms of anxiety and swimming performance over 120h of exposure and multiple repeated doses of both Polyethylene and Polypropylene microplastics. Polyethylene showed an anxiogenic potential, while Polypropylene exhibited an anxiolytic potential at the first two doses. In terms of swimming performance, an increase of specific parameters was observed throughout the repeated doses in the case of Polyethylene, whereas in the case of Polypropylene they decrease. These results were compared with those from the specialized existing literature on the effects of some of the most common hallucinogenic and psychoactive substances. Our results highlight that the mechanism of action of the aforementioned materials is different and show toxic effects from the first dose. Polyethylene has a similar outcome to the one in the case of some substances, especially hallucinogenic, such as LSD, mescaline, MDMA, phencyclidine, and nicotine. On the other hand, polypropylene has a similar effect to psychoactive drugs, cannabidiol, tetrahydrocannabinol, but also MDMA at certain doses. Bases on these observations, further studies should be conducted on the similarities of the detrimental effects.