Search Results (17)

Background/Objectives: Major depressive disorder (MDD) is a debilitating illness, and chronic stress is a contributing factor for depressive symptoms. However, despite intense research, the mechanisms of MDD remain substantially unidentified. Quercetin is a powerful flavonoid and could be used as a possible therapeutic strategy for depression. Acknowledging the potential benefits of quercetin, this study investigated its effect alone or in association with the standard drug tranylcypromine (TCP) in a rodent model of chronic restraint stress (CRS). Methods: Adult male rats were subjected to a CRS model consisting of an immobilization session of 4 h daily during 14 consecutive days. Quercetin (50 mg/kg, gavage) was administered for 45 days. TCP (10 mg/kg, gavage) was administered for 14 days. Behavioral tasks were conducted to assess locomotor functions, memory, anhedonia, depression-like behaviors, and anxiety-like behaviors. The activity, gene expression, and protein density of acetylcholinesterase (AChE) were investigated. Results: Behavioral tasks showed that the CRS model effectively induced stable behavioral changes. CRS did not alter locomotor function assessed by the open field test (OFT) or anhedonia behavior assessed by the sucrose preference test (SPT). CRS increased total fecal count, which was prevented by quercetin administration in rats. TCP and the association of quercetin and TCP increased the recognition index in comparison with the CRS group in the novel object recognition (NOR) test and improved the swimming and immobility times in comparison to stressed animals in the forced swim test (FST). All treatments were able to decrease the anxiety index assessed by the elevated plus maze (EPM) test. The activity, gene expression, and protein density of AChE were increased in the CRS model compared to control males. Overall, quercetin and TCP proved to reverse CRS-induced alterations in these parameters. Conclusions: Quercetin mitigated cognitive deficits, behavioral impairments, and neurochemical alterations induced by the CRS model, especially in association with TCP, supporting its potential as a promising therapeutic agent for depression. Full article

Background/Objectives: Approximately 1% of people worldwide suffer from epilepsy. The development of safer and more effective antiepileptic medications (AEDs) is still urgently needed because all AEDs have some unwanted side effects and roughly 30% of epileptic patients cannot stop having seizures when taking current AEDs. It should be noted that the derivatives of pyrazolo[3,4-b]pyridine are important core structures in many drug substances. The aim of this study is to synthesize new derivatives of piperazino-substituted pyrazolo[3,4-c]-2,7-naphthyridines and 9,11-dimethylpyrimido[1′,2′:1,5]pyrazolo[3,4-c]-2,7-naphthyridines for the evaluation of their neurotropic activity. Methods: The synthesis of the target compounds was performed starting from 1-amino-3-chloro-2,7-naphthyridines and using well-known methods. The structures of all the synthesized compounds were confirmed by spectroscopic data. Compounds were studied for their potential neurotropic activities (anticonvulsant, sedative, anti-anxiety, and antidepressive), as well as side effects, in 450 white mice of both sexes and 50 male Wistar rats. The anticonvulsant effect of the newly synthesized compounds was investigated by using the following tests: pentylenetetrazole, thiosemicarbazide-induced convulsions, and maximal electroshock. The psychotropic properties of the selected compounds were evaluated by using the following tests: the Open Field test, the Elevated Plus Maze (EPM), the Forced Swimming test, and Rotating Rod Test to study muscle relaxation. For the docking studies, AutoDock 4 (version 4.2.6) was used, as well as the structures of the GABA_A receptor (PDB ID: 4COF), the SERT transporter (PDB ID: 3F3A), and the 5-HT_1A receptor (PDB ID: 3NYA) obtained from the Protein Data Bank. Results: A series of piperazino-substituted pyrazolo[3,4-c]-2,7-naphthyridines (3a–j) and 9,11-dimethylpyrimido[1′,2′:1,5]pyrazolo[3,4-c]-2,7-naphthyridines (4a–j), as well as new heterocyclic systems, i.e., isoxazolo[5,4-c]-2,7-naphthyridines 6a–d, were synthesized and evaluated for their neurotropic activity. The investigation showed that some of these compounds (3a,b,d,f–i and 4a,d,f,i) display high anticonvulsant activity, especially in the test of antagonism with pentylenetetrazol, surpassing the well-known antiepileptic drug ethosuximide. Thus, the most active compounds in the pentylenpotetrazole test are 3h, 3i, and 4i; the ED50 of compound 4i is 23.8, and the therapeutic index is more than 33.6, which is the highest among these three active compounds. On the other hand, they simultaneously exhibit psychotropic (anxiolytic, antidepressant, or sedative) or behavioral depressant) effects. The effective compounds do not cause myorelaxation at the tested doses and have high therapeutic indices. Docking on the most active compounds, i.e., 3h, 3i, and 4i, is in agreement with the experimental results. Conclusions: The studies reveled that some of these compounds (3i, 4a, and 4i) display high anticonvulsant and psychotropic activities. The most active compounds contained methyl and diphenylmethyl groups in the piperazine ring. The docking studies identified compounds 3i, 4i, and 4a as the most potent anticonvulsants, showing strong affinity for GABA_A, 5-HT_1A receptors, and the SERT transporter. Notably, compound 4i formed two hydrogen bonds with Thr176 and Arg180 on GABA_A and exhibited a binding energy (−8.81 kcal/mol) comparable to that of diazepam (−8.90 kcal/mol). It also showed the strongest binding to SERT (−7.28 kcal/mol), stabilized by interactions with Gly439, Ile441, and Arg11. Furthermore, 4i displayed the best docking score with 5-HT_1A (−9.10 kcal/mol) due to multiple hydrogen bonds and hydrophobic interactions, supporting its potential as a dual-acting agent targeting both SERT and 5-HT_1A. Full article

Background/Objectives: Diabetes mellitus is often accompanied by mental health complications, including anxiety, depression, and cognitive decline. Recent research suggested that capsaicin, the active component of chili peppers, may influence mental health. This study aimed to determine the effect of dietary capsaicin on mental disorders in a type 1 diabetes (T1D) mouse model, while also exploring the potential involvement of the microbiota-gut-brain axis. Methods: We induced T1D in mice using streptozotocin (STZ) and administered a diet supplemented with 0.005% capsaicin for five weeks. Behavioral assessments, including the open field test (OFT), tail suspension test (TST), forced swimming test (FST), elevated plus maze (EPM) test, and Morris water maze (MWM) test, were conducted to evaluate depressive and anxiety-like behaviors as well as cognitive function. Targeted and untargeted metabolomics analyses were performed to assess neurotransmitter levels in the hippocampus and serum metabolites, while 16S rRNA sequencing was utilized to analyze gut microbiota composition. Intestinal barriers were determined using western blot detection of the tight junction proteins ZO-1 and occludin. Results: Dietary capsaicin exacerbated anxiety and depressive-like behaviors along with cognitive declines in T1D mice. Capsaicin reduced gut microbiota diversity and levels of beneficial bacteria, while broad-spectrum antibiotic treatment further intensified anxiety and depression behaviors. Metabolomic analysis indicated that capsaicin disrupted metabolic pathways related to tryptophan and phenylalanine, leading to decreased neuroprotective metabolites, such as kynurenic acid, hippurate, and butyric acid. Additionally, capsaicin diminished the expression of ZO-1 and occludin, indicating increased intestinal permeability. Conclusions: Dietary capsaicin aggravates gut microbiota and metabolic disturbances in diabetic mice, thereby worsening anxiety, depression, and cognitive decline. Full article

Understanding the behavior of carbon dioxide (CO₂) under varying thermodynamic conditions is essential for optimizing processes such as Carbon Capture and Storage (CCS) and supercritical fluid extraction. This study employs molecular dynamics (MD) simulations with the EPM2 and TraPPE-small force fields to examine CO₂ phase behavior, structural characteristics, and transport properties across a temperature range of 228–500 K and pressures from 1 to 150 atm. Our findings indicate a good agreement between simulated and experimental liquid–vapor coexistence curves, validating the capability of both force fields to model CO₂ accurately in a wide range of thermodynamical conditions. Radial distribution functions (RDFs) reveal distinct interaction patterns in liquid and supercritical phases, while mean squared displacement (MSD) analyses show diffusivity increasing from $5.2\times {10}^{-9}$ m²/s at 300 K to $1.8\times {10}^{-8}$ m²/s at 500 K. Additionally, response functions such as the heat capacity effectively capture phase transitions. These findings provide quantitative insights into CO₂ phase behavior and transport properties, enhancing the predictive reliability of simulations for CCS and related industrial technologies. This work bridges gaps in the CO₂ modeling literature and highlights the potential of MD simulations in advancing sustainable applications. Full article

To investigate the effects of one-week maternal separation (MS) on anxiety- and depression-like behaviors in adolescent and adulthood as well as adult hippocampal metabolomics simultaneously in offspring female and male rats. In the MS group, newborn SD rats were separated from their mothers for 3 h per day from postnatal days (PND) 2 to 8. The open field test (OFT), elevated plus mazes (EPM), novelty suppressed feeding test (NSFT), and forced swimming test (FST) were conducted during adolescence and adulthood. Serum corticosterone, mRNA expression of hippocampal inflammatory cytokines, and hippocampal untargeted metabolomics of offspring adult rats were examined using an assay kit, qRT-PCR, and UPLC-Q-TOF/MS. Both MS female and male rats showed similar behaviors in OFT, EPM, NSFT, and SPT, except for the latency to feeding during adolescence and the open arm entries during adulthood, showed statistical significance only in MS female rats. Serum corticosterone and hippocampal pro-inflammatory cytokines IFN-γ were significantly elevated in both female and male rats, and IL-1β and TNF-α were significantly increased only in female rats. In hippocampal metabolism, the identification of differential metabolites displayed 53 and 37 in female rats and male rats, respectively (with 35 common metabolites), which were involved in 33 and 30 metabolic pathways with 28 common pathways. One-week MS induced sex-specific anxiety- and depression-like behaviors in female and male offspring rats during adolescence and adulthood, as well as sex-differentiated characteristics in the hippocampus inflammatory cytokines and metabolomics of adult MS rats. From the experimental data, the effects of MS on the female offspring rats were more severe than those of the male offspring rats. Full article

Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group (p < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine (p < 0.05 central zone; p ≤ 0.05 periphery zone) and SMe1EC2M3 (p < 0.05 central zone; p < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST (p < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group (p < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group (p < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD. Full article

Mental and neurological disorders are conditions that affect thoughts, emotions, behavior, and relationships. Malpighia mexicana A. Juss. is a plant used in Mexican traditional medicine for the treatment of such disorders. This work aimed to investigate the antidepressant, anxiolytic, sedative, hypnotic, and anticonvulsant effects of the acetonic extract (MmAE) of M. mexicana and its fractions (F3, F4-10, F14) using the forced swimming test (FST), elevated plus maze (EPM), open field test (OFT), pentobarbital-induced sleep test (PBTt), and pentylenetetrazol-induced seizure test (PTZt). MmAE, F3, F4-10, F14, and vehicle were administrated orally 24, 18, and 1 h prior to the evaluations. Imipramine (15 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the FST, while diazepam (1 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the EPM, OFT, PBTt, and PTZt. MmAE had an anxiolytic effect; MmAE and F3, F4-10, and F14 showed an antidepressant effect, sedative effect, hypnotic effect, and anticonvulsant effect. Using HPLC, we identified the compounds quercetin 3-O-rutinoside (1), kaempferol 3-O-glucoside (2), luteolin 7-O-glucoside (3), quercetin (4), and kaempferol (5) in MmAE and compounds (1), (2), and (3) in F14. Using GC-MS, we identified α-tocopherol, phytol, and β-amyrin in F3; β-tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10; and α- tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10. The neuropharmacological effects found in this work may be due to the presence of vitamins, phytosterols, terpenes, and flavonoids. This research requires further study to clarify the mechanisms of action of the identified compounds. Full article

The dynamic characteristics of sandwich panels with a hierarchical hexagonal honeycomb (SP-HHHs) show significant improvements due to their distinct hierarchy configurations. However, this also increases the complexity of structural analysis. To address this issue, the variational asymptotic method was utilized to homogenize the unit cell of the SP-HHH and obtain the equivalent stiffness, establishing a two-dimensional equivalent plate model (2D-EPM). The accuracy and effectiveness of the 2D-EPM were then verified through comparisons with the results from a detailed 3D FE model in terms of the free vibration and frequency- and time-domain forced vibration, as well as through local field recovery analysis at peak and trough times. Furthermore, the tailorability of the typical unit cell was utilized to perform a parametric analysis of the effects of the length and thickness ratios of the first-order hierarchy on the dynamic characteristics of the SP-HHH under periodic loading. The results reveal that the vertices serve as weak points in the SP-HHH, while the vertex cell pattern significantly influences the specific stiffness and stiffness characteristics of the panel. The SP-HHH with hexagonal vertex cells has superior specific stiffness compared to panels with circular and rectangular vertex cells, resulting in a more lightweight design and enhanced stiffness. Full article

Depression is a psychiatric disorder that negatively affects how a person feels, thinks, and acts. Several studies have reported a positive association between vitamin D (VD) deficiency and depression. Therefore, we aimed to examine the effects of intraperitoneal injection of VD3, fluoxetine (antidepressant), and a combination of VD3 + fluoxetine on a rat model of chronic unpredictable mild stress (CUMS). A total of 40 male Wistar rats (224–296 g) were divided into five groups (n = 8 each) as follows: (1) the control group, (2) the CUMS group, (3) the CUMS group that received vitamin D (10 μg/kg), (4) the CUMS group that received fluoxetine (5 mg/kg), and (5) the CUMS group that received both vitamin D (10 μg/kg) and fluoxetine (5 mg/kg). The CUMS model was produced by exposing rats to frequent social and physical stressors for 21 days. In addition, blood samples were collected to determine corticosterone and serum VD levels. Also, behavioral tests were conducted, including the sucrose preference test (SPT), the forced swimming test (FST), the tail suspension test (TST), the open field test (OFT), and the elevated plus maze test (EPM). Our results show that VD3 had effects similar to fluoxetine on the depressive behavior of the rats when measured by three behavioral tests, namely SPT, FST, and OFT (p < 0.001). Additionally, VD3 had a protective effect against depression similar to that of fluoxetine. Corticosterone levels were lower in the CUMS group that received vitamin D and the CUMS group that received both vitamin D and fluoxetine than in the CUMS group (p < 0.000). In conclusion, VD3 has a protective effect against anxiety and depressive behaviors produced by CUMS in rats. Full article

Eriobotrya japonica (loquat tree) has been used in traditional medicine to treat respiratory ailments, inflammation, and skin diseases; however, its potential antidepressant-like effects have not been extensively investigated. In this study, we evaluated the antidepressant-like effects of E. japonica fruit extract (EJFE) in a mouse model of corticosterone (CORT)-induced depression. An HPLC analysis revealed that chlorogenic acid (CGA) is the major compound in EJFE. Male ICR mice (5weeks-old) were injected with CORT (40 mg/kg, intraperitoneally) once daily for 21 days to induce depressive-like behaviors. Various behavioral tests, including the open field test, rotarod test, elevated plus maze (EPM), passive avoidance test (PAT), tail suspension test (TST), and forced swim test (FST), were conducted 1 h after the oral administration of EJFE at different doses (30, 100, and 300 mg/kg) and CGA (30 mg/kg). High-dose EJFE and CGA significantly alleviated CORT-induced depressive-like behaviors, as indicated by the reduced immobility times in the TST and FST. A decrease in the step-through latency time in the PAT, without an effect on locomotor activity, suggested an improvement in cognitive function. Moreover, EJFE- and CGA-treated mice exhibited significantly reduced anxiety-like behaviors in the EPM. Our results imply the promising potential of EJFE containing CGA as a therapeutic candidate for depression. Full article

Depression-induced cognitive impairment has recently been given more attention in research. However, the relationship between depression and different types of memory is still not clear. Chronic unpredictable mild stress (CUMS) is a commonly used animal model of depression in which animals are exposed to chronic unpredictable environmental and psychological stressors, which mimics daily human life stressors. This study investigated the impact of different durations of CUMS on various types of memory (short- and long-term spatial memory and recognition memory) and investigated CUMS’ impact on the ultrastructural level by histological assessment of the hippocampus and prefrontal cortex. Twenty male C57BL/J6 mice (6 weeks old, 21.8 ± 2 g) were randomly divided into two groups (n = 10): control and CUMS (8 weeks). A series of behavioral tasks were conducted twice at weeks 5–6 (early CUMS) and weeks 7–8 (late CUMS). A tail-suspension test (TST), forced swimming test (FST), elevated zero maze (EZM), elevated plus maze (EPM), open field test (OFT), and sucrose-preference test (SPT) were used to assess anxiety and depressive symptoms. The cognitive function was assessed by the novel object recognition test (NORT; for recognition memory), Y-maze (for short-term spatial memory), and Morris water maze (MWM: for long-term spatial memory) with a probe test (for reference memory). Our data showed that 8 weeks of CUMS increased the anxiety level, reported by a significant increase in anxiety index in both EPM and EZM and a significant decrease in central preference in OFT, and depression was reported by a significant increase in immobility in the TST and FST and sucrose preference in the SPT. Investigating the impact of CUMS on various types of memory, we found that reference memory is the first memory to be affected in early CUMS. In late CUMS, all types of memory were impaired, and this was consistent with the abnormal histological features of the memory-related areas in the brain (hippocampus and prefrontal cortex). Full article

Background: Heterocyclic compounds and their fused analogs, which contain pharmacophore fragments such as pyridine, thiophene and pyrimidine rings, are of great interest due to their broad spectrum of biological activity. Chemical compounds containing two or more pharmacophore groups due to additional interactions with active receptor centers usually enhance biological activity and can even lead to a new type of activity. The search for new effective neurotropic drugs in the series of derivatives of heterocycles containing pharmacophore groups in organic, bioorganic and medical chemistry is a serious problem. Methods: Modern methodology of drugs involves synthesis, physicochemical study, molecular modeling and selection of active compounds through virtual screening and experimental evaluation of the biological activity of new chimeric compounds with pharmacophore fragments. For the synthesis of new compounds, classical organic methods were used and developed. For the evaluation of neurotropic activity of new synthesized compounds, some biological methods were used according to indicators characterizing anticonvulsant, sedative and antianxiety activity as well as side effects. For docking analysis, various soft ware packages and methods were used. Results: As a result of multistep reactions, 11 new, tri- and tetracyclic heterocyclic systems were obtained. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures as well as some psychotropic effects. The biological assays evidenced that nine of the eleven studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of the compounds is low, and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity, it was found that the selected compounds have an activating behavior and anxiolytic effects on the “open field” and “elevated plus maze” (EPM) models. The data obtained indicate the anxiolytic (antianxiety) activity of the derivatives of tricyclic thieno[2,3-b]pyridines and tetracyclic pyridothieno[3,2-d]pyrimidin-8-ones, especially pronounced in compounds 3b–f and 4e. The studied compounds increase the latent time of first immobilization on the “forced swimming” (FS) model and exhibit antidepressant effects; compounds 3e and 3f especially exhibit these effects, similarly to diazepam. Docking studies revealed that compounds 3c and 4b bound tightly in the active site of γ-aminobutyric acid type A (GABA_A) receptors with a value of the scoring function that estimates free energy of binding (∆G) at −10.0 ± 5 kcal/mol. Compound 4e showed the best affinity ((∆G) at −11.0 ± 0.54 kcal/mol) and seems to be an inhibitor of serotonin (SERT) transporter. Compounds 3c–f and 4e practically bound with the groove of T4L of 5HT_1A and blocked it completely, while the best affinity observed was in compound 3f ((∆G) at −9.3 ± 0.46 kcal/mol). Conclusions: The selected compounds have an anticonvulsant, activating behavior and anxiolytic effects and at the same time exhibit antidepressant effects. Full article

Background: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. Objective: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. Methods: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. Results: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of “open field” and “elevated plus maze” (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of “forced swimming” (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABA_A receptor with a value of the scoring function that estimates free energy of binding (ΔG) at −7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT_1A receptor. Conclusions: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect. Full article

Background and Objectives: Ficus benghalensis (FB) is a commonly found tree in Pakistan and its various parts have folkloric importance in managing neurological ailments. In the present study, methanolic extract of its bark has been tested on an experimental animal model to evaluate memory-enhancing, anxiolytic and antidepressant activities to validate the claimed therapeutic potential. Materials and Methods: Methanolic extract of freshly isolated bark was prepared and subjected to preliminary phytochemical studies and gas chromatography–mass spectrometry (GC–MS) analysis for the presence of phytocomponents. To evaluate its effect on spatial learning, passive-avoidance test–step through (PAT-ST), Y-maze and Morris water maze (MWM) tests were carried out. Open-field (OFT) and elevated plus maze (EPM) tests were employed to explore the anti-anxiety potential of FB while a forced swimming test (FST) was utilized to assess its anti-depressant prospective. FB doses of 100, 200 and 300 mg/kg with positive and negative controls given to Sprague Dawley (SD) rats. Results: phytochemical studies showed the presence of various phytoconstituents including alkaloids, flavonoids, terpenes, phenolics and anthraquinones. The presence of synephrine, aspargine, glucose, fructose and fatty acids was revealed by GC–MS analysis. FB administration led to significant improved memory retention when evaluated through passive avoidance (p < 0.05), Y-maze (p < 0.05) and Morris water maze (p < 0.05) tests in a scopolamine model of amnesic rats. When tested by open field and elevated plus maze tests, FB demonstrated anxiety-resolving characteristics (p < 0.05) as animals dared to stay in open areas more than a control group. Mobility time was increased and immobility time was reduced (p < 0.05–0.01) in rats treated with FB, unveiling the anti-depressant importance of F. benghalensis. Conclusion: methanolic extract of F. benghalensis bark furnished scientific proof behind folkloric claims of the memory improving, anxiety-reducing and depression-resolving characteristics of the plant. These activities might be possible due to interaction of its phytoconstituents with serotonergic, glutamatergic, cholinergic and GABAergic systems in the brain. Full article

In our previous investigation, we found that agarwood essential oil (AEO) has a sedative-hypnotic effect. Sedative-hypnotic drugs usually have an anxiolytic effect, where concomitant anxiety and depression are a common comorbidity. Therefore, this study further investigated the anxiolytic and antidepressant effects of AEO using a series of animal behavior tests on a restraint stress-induced mice model. The elevated plus maze (EPM) test, the light dark exploration (LDE) test, and the open field (OF) test demonstrated that AEO has a significant anxiolytic effect. Simultaneously, the tail suspension (TS) test and the forced swimming (FS) test illuminated that AEO has an antidepressant effect with the immobility time decreased. Stress can cause cytokine and nitric oxide (NO) elevation, and further lead to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. AEO was shown to dose-dependently inhibit the levels of cytokines, including interleukin 1α (IL-1α), IL-1β, and IL-6 in serum, significantly decrease the mRNA level of neural nitric oxide synthase (nNOS) in the cerebral cortex and hippocampus, and inhibit the nNOS protein level in the hippocampus. Concomitant measurements of the HPA axis upstream regulator corticotropin releasing factor (CRF) and its receptor CRFR found that AEO significantly decreases the gene expression of CRF, and significantly inhibits the gene transcription and protein expression of CRFR in the cerebral cortex and hippocampus. Additionally, AEO dose-dependently reduces the concentrations of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) downstream of the HPA axis, as measured by ELISA kits. These results together demonstrate that AEO exerts anxiolytic and antidepressant effects which are related to the inhibition of CRF and hyperactivity of the HPA axis. Full article