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Background: There is renewed interest in the use of ancient herbal remedies for their potential health benefits, particularly in the psychological domain. One herb that is receiving growing attention is lemon balm (Melissa officinalis L.) which has received considerable interest for its influence on the brain. Lemon balm boasts an array of phytochemicals, including rosmarinic acid, citral, oleanolic acid, and ursolic acid, which are believed to underpin these effects on psychological well-being. Pharmacological evidence from animal and cellular work reveals that lemon balm and its components may modulate several brain signalling pathways, including GABAergic, cholinergic, and serotonergic systems. Results/Conclusions: Although further robust randomised controlled trials using lemon balm are required, existing research indicates that lemon balm holds promise as a calming agent exhibiting both anxiolytic and anti-depressant properties and can elicit cognitive and sleep-quality enhancement. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the proportion of Australians dispensed psychotropic medications between 2013 and 2022 according to their age. Methods: Services Australia provided a de-identified 10% random Pharmaceutical Benefits Scheme sample that allowed us to determine, for each year, the proportion of Australians dispensed at least one script for antipsychotics, antidepressants, anxiolytics, or hypnotics. The classification of medications followed Anatomical Therapeutic Chemical coding. Participants were stratified into 10-year age groups from 0–9 to ⩾90 years, and sex was coded as male/female. We retrieved population numbers from the Australian Bureau of Statistics. Results: The number of records per year ranged from 1,540,520 to 1,746,402, and 54.10% were for females. A greater proportion of older adults, particularly those aged ⩾70 years, were dispensed antipsychotics, antidepressants, anxiolytics and hypnotics than any other age group. The proportion of people who dispensed antipsychotics, anxiolytics and hypnotics declined between 2013 and 2022 but increased for antidepressants, most markedly for adolescents and young adults. Females were more frequently dispensed antidepressants, anxiolytics and hypnotics than males, but males were more frequently dispensed antipsychotics than females, albeit not in later life. Conclusion: Older age groups and females are the most frequent recipients of psychotropic medications dispensed in Australia. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we aimed to examine the effects of chotosan, a traditional Japanese botanical drug, and its active component, Uncaria hook, on anxiety-like behaviors induced by systemic inflammation in mice. Methods: To induce systemic inflammation, the mice were treated with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS treatment, the mice were administered chotosan or Uncaria hook orally each day for 14 days. Anxiety-like behavior of the mice was evaluated using the light--dark test 24 h after LPS treatment. Results: Repeated administration of chotosan prevented anxiety-like behavior in both normal and LPS-treated mice. Similarly, administration of Uncaria hook suppressed LPS-induced anxiety-like behavior in mice. Furthermore, treatment with tandospirone, a 5-HT1A receptor agonist, alleviated anxiety-like behavior in mice, whereas treatment with DOI, a 5-HT2A receptor agonist, enhanced anxietylike behavior in mice. LPS treatment significantly increased serotonin (5-HT)2A receptor mRNA expression in the frontal cortex, whereas 5-HT1A receptor mRNA expression remained unchanged in the hippocampus. Notably, chotosan significantly suppressed the mRNA expression of 5-HT2A receptor. Discussion: These findings indicate that chotosan exerts anxiolytic-like effects in the context of inflammation-induced anxiety, potentially mediated by the inhibition of 5-HT2A receptor hyperfunction in LPS-treated mice. Consequently, we postulate that chotosan may be effective in managing inflammation-induced anxiety-like behaviors. [ABSTRACT FROM AUTHOR]

To examine cross-sectional and longitudinal relationships of psychotropic medications with physical function after menopause. Analyses involved 4557 Women's Health Initiative Long Life Study (WHI-LLS) participants (mean age at WHI enrollment (1993–1998): 62.8 years). Antidepressant, anxiolytic, and sedative/hypnotic medications were evaluated at WHI enrollment and 3-year follow-up visits. Performance-based physical function [Short Physical Performance Battery (SPPB)] was assessed at the 2012–2013 WHI-LLS visit. Self-reported physical function [RAND-36] was examined at WHI enrollment and the last available follow-up visit—an average of 22 [±2.8] (range: 12–27) years post-enrollment. Multivariable regression models controlled for socio-demographic, lifestyle, and health characteristics. Anxiolytics were not related to physical function. At WHI enrollment, antidepressant use was cross-sectionally related to worse self-reported physical function defined as a continuous (β = −6.27, 95% confidence interval [CI]: −8.48, −4.07) or as a categorical (< 78 vs. ≥ 78) (odds ratio [OR] = 2.10, 95% CI: 1.48, 2.98) outcome. Antidepressant use at WHI enrollment was also associated with worse performance-based physical function (SPPB) [< 10 vs. ≥ 10] (OR = 1.53, 95% CI: 1.05, 2.21) at the 2012–2013 WHI-LLS visit. Compared to non-users, those using sedative/hypnotics at WHI enrollment but not at the 3-year follow-up visit reported a faster decline in physical function between WHI enrollment and follow-up visits. Among postmenopausal women, antidepressant use was cross-sectionally related to worse self-reported physical function, and with worse performance-based physical function after > 20 years of follow-up. Complex relationships found for hypnotic/sedatives were unexpected and necessitate further investigation. [ABSTRACT FROM AUTHOR]

Hongqing Zhao,1,2,&ast; Yang Liu,1,2,&ast; Na Cai,3 Xiaolin Liao,1,2 Lin Tang,2,4 Yuhong Wang1,2 1Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Hunan Key Laboratory of Traditional Chinese Medicine Prevention & Treatment of Depressive Diseases, Changsha, Hunan, People’s Republic of China; 3Outpatient Department, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 4Department of Pharmacy, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Tang; Yuhong Wang, Email tanglin0018@163.com; wangyh107@126.comAbstract: Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.Keywords: endocannabinoid hydrolase inhibitors, endocannabinoid system, anxiety disorders, anxiolytic, MAGL, FAAH

Purpose: Buspirone, an anxiolytic with minimal risk of dependence or respiratory depression, lacks extensive published data on its transfer into human milk during lactation. The objective of this study was to 1) quantify the transfer of buspirone and its active metabolite 1-pyrimidinylpiperazine (1-PP) into human milk, allowing for an estimation of maternal drug exposure to the breastfed infant, and 2) report observations of the infants exposed to buspirone via breastmilk. Methods: Milk samples and health histories were collected from nine lactating mothers who donated milk samples to the InfantRisk Human Milk Biorepository while taking buspirone. The drug concentration–time profile of buspirone and 1-PP was determined using liquid chromatography–mass spectrometry. Results: Buspirone was below the detection level of 1.5 ng/mL in all milk samples with dosages ranging from 7.5 to 30 mg twice daily. However, low levels of active metabolite 1-PP were observed at 7.5 mg twice daily up to 30 mg twice daily. The relative infant dose (RID) calculated ranged from 0.21 to 2.17%, which is below the standard 10% threshold for infant safety. There were no reports of adverse effects in the exposed infants. Conclusion: The levels of buspirone observed in all participants' milk samples were exceedingly low. The subsequently low relative infant dose (RID) in the range of 0.21% to 2.17% is below the 10% threshold for infant safety, suggesting that the transfer of maternal buspirone and its active metabolite (1-PP) into human milk is clinically insignificant and poses minimal risk to a breastfed infant. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines for various psychiatric disorders recommend short-term use of benzodiazepine anxiolytic monotherapy in few cases. Contrarily, benzodiazepine anxiolytic polypharmacy (BAP) is not recommended in any case. However, BAP is often used in real world. Therefore, this study aimed to determine the association between BAP and concomitant use of psychotropic medications. Method: This retrospective cross-sectional study used claims data from the Japan Medical Data Center. Medical information of health insurance subscribers treated with benzodiazepine anxiolytics in June 2019 was extracted. Prescription of two or more benzodiazepine anxiolytics was defined as BAP. Binary logistic regression analysis was performed to investigate the factors associated with BAP, using age group, sex, type of subscriber, and number of concomitant hypnotics, antidepressants, and antipsychotics (none, one, and two or more) as covariates. Result: The eligible participants were 104,796 adults who were prescribed benzodiazepine anxiolytics. Among them, 12.6% were prescribed two or more drugs. Logistic regression analysis revealed that BAP was significantly associated with those who received hypnotic monotherapy (adjusted odds ratio [aOR]: 1.04, 95% confidence interval [CI]: 1.001-1.09, p=0.04), antidepressant monotherapy and polypharmacy (aOR: 1.57, 95% CI: 1.51-1.63, p<0.001 and aOR: 1.98, 95% CI: 1.88-2.09, p<0.001, respectively), and antipsychotic monotherapy and polypharmacy (aOR: 1.12, 95% CI: 1.07-1.19, p<0.001 and aOR: 1.41, 95% CI: 1.30-1.54, p<0.001, respectively). Conversely, lower BAP was associated with those who received hypnotic polypharmacy (aOR: 0.86, 95% CI: 0.81-0.91, p<0.001). Discussion: This study showed that the greater the number of concomitant antidepressants and antipsychotics, the greater the association with BAP. Since combination therapy with antidepressants or antipsychotics is generally not recommended, patients receiving combination therapy with these medications may be resistant to pharmacotherapy. Therefore, implementing the recommended non-pharmacological treatments may reduce BAP. [ABSTRACT FROM AUTHOR]

Due to the health benefits of polyphenols and dietary fiber in combating mental disorders, we hypothesized that a polyphenol- and dietary fiber-enriched soup (RJ6601) would improve mental wellness in a rat model of middle-aged women. To test this hypothesis, female Wistar rats aged 18 months (350–450 g) were orally administered RJ6601 at doses of 200 and 400 mg/kg BW for 28 days. The anxiolytic, antidepression, and memory-enhancing effects were assessed every 7 days throughout the study period. The neuron density and levels of activities of AChE, total MAO, MAO-A, MAO-B, MDA, SOD, CAT, GSH-Px, IL-1β, IL-6, and BDNF in the prefrontal cortex at the end of study were also investigated. Furthermore, the amounts of Lactobacillus spp. and Bifidobacterium spp. in their feces were also determined. The results revealed that the developed soup shows anxiolytic, antidepression, and memory-enhancing effects. An increased neuron density; reductions in AChE, total MAO, MAO-A, MAO-B, and MDA; and an elevation of serum BDNF, together with increased amounts of both bacterial species in feces, were also observed. Our results suggest that RJ6601 is a potential mental wellness promotion supplement that enhances BDNF levels, brain plasticity, neurotransmitter balance, and oxidative stress and inflammation status, along with improving microbiota. [ABSTRACT FROM AUTHOR]

Background and objective: Since plant-based natural drugs are widely accepted in modern times and possess numerous pharmacological effects with an extensive therapeutic range, an ethnomedicinal plant native to Bangladesh was selected to investigate for investigation of its various pharmacological effects. Macropanax dispermus has been traditionally used and has demonstrated numerous pharmacological effects in preclinical investigations. Therefore, this research aimed to assess the central nervous system (CNS) depressant and antioxidant activities of the crude methanol extracts of the stem barks (MDMS), leaves (MDML), and their different fractions. Methods : The CNS depressant activity was assessed using the hole cross, rota-rod, and elevated plus maze tests on Swiss Albino mice, while the antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl free radical, hydrogen peroxide (H2O2) nonradical scavenging, and ferric reducing power assays. Results: The conducted assays successfully demonstrated that the chloroform fraction of MDML is a significantly ( P < 0.001) effective CNS depressant, muscle relaxant, and anxiolytic agent with excellent antioxidative effects compared to standard and control. The aqueous fraction of MDML also acted as a significantly ( P < 0.001) active CNS depressant and muscle relaxant, and it was a highly active ferric-reducing agent. All effects were dose and concentrationdependent. Conclusion: The presence of various phytochemicals might contribute to these activities. However, further research is suggested to isolate their active compounds and evaluate their mechanisms of action. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Brassaiopsis palmata, an androgynous tree from Araliaceae family, has been widely found in the Asian subcontinent, and reported to have potentiality against skin infection, and many therapeutic properties still unidentified. Here, our current investigation aims to discover the innovative pharmacological potentials of the methanol extract of B. palmata leaves (MEBPL) through in‐vivo and in‐vitro approaches. Several secondary metabolites were revealed throughout the qualitative phytochemical screening of the plant extracts. MEBPL exhibited strong radical scavenging properties (IC50 178.13 µg/mL) through the 2, 2‐diphenyl‐1‐picryhydrazyl (DPPH) assay, and through the quantitative (phenolic and flavonoid) assays with a moderate (LD50 153.14 µg/mL) toxic effect. In anti‐inflammatory screening, MEBPL showed significant dose dependent inhibitory activity; and the peak inhibition were found 78.01 ± 1.22% and 82.46 ± 1.52% at 1000 µg/mL concentration on hypotonic‐induce RBC hemolysis & protein denaturation test respectively. Moreover, the plant extracts manifested moderate percentage of clot lysis (28.24 ± 2.50%) on the investigation of thrombolytic assay. The anti‐nociceptive activity of MEBPL was analyzed through acetic acid and formalin induce pain tests. Both 200 and 400 mg/kg dose of MEBPL exerted significant (p ˂ 0.001) dose depending depletion of acetic acid induced writhing and formalin stimulated licking test which indicated strong analgesic properties of plant extracts. In addition, the outcomes of anti‐depressant evaluation suggested that treatment with both 200 and 400 mg/kg doses showed potential dose depending activity on both FST and TST model. Furthermore, the plant extracts manifested dose dependent reduction of anxiety like behaviors in the rodent model. Particularly, mice administrated with 400 mg/kg dose of MEBPL significantly (p ˂ 0.05) enhanced the percentage of entries and time spent in the open arm in EPM, and also showed the highest amount of head dipping tendency in HBT. In contrast, the outcomes of this research suggest that B. palmata could be another source of antioxidant, cytotoxic, anti‐inflammatory, thrombolytic, anti‐nociceptive, anti‐depressant, and anxiolytic agents. Further research on the mechanisms underlying bioactivities is required.

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The medicinal potential of Coelogyne suaveolens, a traditional medicinal plant, was investigated through in vivo and molecular docking studies. The ethyl acetate fraction of the plant's acetonic extract was subjected to various bioactivity tests to assess its analgesic, anxiolytic, and sedative effects on Swiss albino mice. Furthermore, we used GCMS to identify the bioactive chemicals in the extract's ethyl acetate fraction. The root and bulb extracts demonstrated significant analgesic activity in acetic acid‐induced writhing, hot plate, and tail immersion tests in a dose‐dependent manner when compared to the control. Again, the extract exhibited moderate anxiolytic activity in the elevated plus maze test at a dosage of 400 mg/kg body weight, while the root extract showed significant anxiolytic activity in the hole board test at the same dosage. Significant sedative activity was observed in the hole cross, open field, and rotarod tests at a dosage of 400 mg/kg. According to molecular docking studies, the extract has the potential to serve as an analgesic medication by reducing the enzymatic activity of cyclooxygenases 1 and 2. Overall, the findings suggest that C. suaveolens has substantial therapeutic potential for the development of novel treatments for pain, anxiety, and sleep disorders. [ABSTRACT FROM AUTHOR]

The original article was published in Veterinary Evidence Vol 9, Issue 1 (2024): https://doi.org/10.18849/ve.v9i1.679 In the original version of the article the contributions of one of the authors, Christopher Minami, were listed as "Investigation, Writing – Original draft". This has now been corrected to accurately reflect Minami's contributions, with the agreement of all the authors: Christopher Minami: Conceptualisation, Methodology, Investigation, Writing – Original draft. This error was in both the HTML and PDF versions. This has now been updated in both the HTML and PDF versions, and can be found in the author contributions section.

Abstract Background Conditions affecting the hypothalamic‐pituitary‐adrenal (HPA) axis are common in dogs. Testing the function of the HPA axis includes measurement of endogenous adrenocorticotropic hormone (eACTH) and performance of an adrenocorticotropic hormone (ACTH) stimulation test. Trazodone is commonly administered to dogs to decrease stress. In humans, trazodone significantly decreases plasma cortisol concentration via alpha‐1 adrenergic activity. Objectives Determine the influence of trazodone on eACTH and serum cortisol concentrations in healthy dogs. Animals Fourteen healthy, adult, companion dogs. Methods Prospective, randomized placebo‐controlled study. Trazodone (8‐10 mg/kg) or placebo was administered PO 1 hour before eACTH measurement and ACTH stimulation testing. After a ≥7‐day wash‐out period, dogs received the opposite treatment. Differences in eACTH, pre‐ and post‐ACTH stimulation cortisol concentrations, and delta (difference between pre‐ and post‐ACTH) cortisol concentrations were analyzed using a paired t or signed‐rank test with a P

Byttneria pilosa, a flowering plant from the Malvaceae family traditionally used to treat ailments such as boils and scabies, is here investigated for its potential health benefits. The study focused on evaluating its antioxidant and antidiabetic properties in vitro, as well as the in vivo anxiolytic and antidepressant activities of the methanol extract of B. pilosa leaf (MEBP). The study employed various assays to evaluate antioxidant activity, including 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, reducing power capacity, and quantification of the total phenolic and flavonoid contents of MEBP. Additionally, anxiolytic and antidepressant activities were evaluated through four tests: elevated plus- maze test (EPMT), light-dark box test (LDBT), forced swimming test (FST), and tail suspension test (TST). Antidiabetic effect was determined using α-amylase inhibition assay. Docking analysis was performed using BIOVIA and Schrödinger Maestro (v11.1), and the absorption, distribution, metabolism, and excretion/ toxicity (ADME/T) properties of bioactive substances were investigated using a web-based technique. MEBP exhibited moderate antioxidant activity in DPPH radical scavenging and reducing power capacity assays, with a dose-dependent response. The total phenolic and flavonoid contents measured were 70 ± 1.53 mg and 22.33 ± 1.20 mg, respectively. MEBP demonstrated significant effects in α- amylase inhibition comparable to acarbose. In behavioral tests, MEBP dose- dependently altered time spent in open arms/light box and closed arms/dark box, indicating anxiolytic effects. Moreover, MEBP significantly reduced immobility duration in FST and TST, suggesting antidepressant properties. Molecular docking analysis revealed favorable interactions between beta-sitosterol and specific targets, suggesting the potential mediation of anxiolytic and antidiabetic effects. Overall, MEBP exhibits notable anxiolytic and antidepressant properties, along with moderate antioxidant and antidiabetic activities. [ABSTRACT FROM AUTHOR]

Simple Summary: Imepitoin is a medication that can be used to treat anxiety in dogs. Previous studies have shown that imepitoin when given at a dose of 30 mg/kg PO BID (milligram per kilogram of body weight by mouth twice a day), can reduce noise-related anxiety in dogs. However, this dosage may be higher than needed for some dogs. We aimed to determine how safe and effective this medication is for the treatment of storm-related fear and anxiety in dogs when started at a lower dose (10 mg/kg PO BID) and, if needed, when increased to a higher dose of 20 or 30 mg/kg PO BID. We determined the three dosages were safe and reduced clinical signs of storm related fear and anxiety in this study design. More side effects were seen in the 20 mg/kg PO BID group than in the 10 mg/kg PO BID group, which supports the use of this medication at an individually titrated dose starting at 10 mg/kg PO BID. Imepitoin is a low-affinity partial agonist for benzodiazepine binding sites of gamma-aminobutyric acid receptors with anxiolytic effects. It has been shown to reduce anxiety during noise-related events in dogs when given at 30 mg/kg PO BID, although this dose was associated with ataxia and increased appetite in some cases. The objective of this study was to assess its safety and efficacy for storm anxiety when started at 10 mg/kg PO BID and titrated to effect up to 30 mg/kg PO BID during storm season. Significant decreases in anxiety scores were seen in weekly surveys and storm logs (SLs) at 10, 20 and 30 mg/kg PO BID. Serious adverse events (AEs) were not reported in any subject. Ataxia was the most commonly reported non-serious AE (14/33), followed by increased hunger (13/33). The frequency of AEs was higher in the 20 mg/kg PO BID group than in the 10 mg/kg group PO BID. No clinically significant changes were seen in lab work pre- and post-study. In conclusion, Imepitoin given during storm season at doses ranging from 10 to 30 mg/kg PO BID reduced clinical signs of fear and anxiety during storms for the dogs in this study. These findings support the use of an individually titrated dose. [ABSTRACT FROM AUTHOR]

• Chronic treatment with Cannabis sativa effectively reversed the behavioral changes induced by chronic unpredictable mild stress. • Anxiolytic and antidepressant effects of the essential oil of Cannabis sativa. • Cannabis sativa essential oil also significantly reduced lipid peroxidation and nitrite levels, increased levels of glutathione, superoxide dismutase, and catalase activities. Cannabis sativa L. is an annual plant from the Cannabaceae family. In Morocco, it has a long-standing traditional use as a sedative and in the treatment of various neurological disorders. This study aimed to investigate the anxiolytic and antidepressant effects of Cannabis sativa essential oil (CSEO) in a mouse model of depression induced by unpredictable chronic stress. Mice were exposed to various stress paradigms to induce depression-like behaviors and were subjected to the Unpredictable Chronic Mild Stress (UCMS) protocol for 30 days. The mice received intraperitoneal doses of 2.5, 5, and 10 mg/kg body weight of CSEO daily. Anhedonia, a key symptom of depression, was assessed using a sucrose preference test, while anxiety and depression-related behaviors were evaluated. Additionally, the oxidative parameters of CSEO, including lipid peroxidation, glutathione peroxidase activity, and catalase, were measured. Results demonstrated that chronic administration of CSEO at 2.5, 5, and 10 mg/kg, effectively reversed the behavioral changes induced by UCMS. CSEO reduced the immobility period and increased sucrose preference in stressed mice, indicating an improvement in depressive symptoms. Moreover, CSEO administration positively impacted the biochemical changes associated with chronic stress, including reduced lipid peroxidation and increased levels of glutathione, superoxide dismutase, and catalase activities. [Display omitted] [ABSTRACT FROM AUTHOR]

Rationale: Using routine synthetic drugs in the treatment of psychiatric disorders may have some restrictions due to serious side effects and pharmacoresistance. Some natural agents may be promising alternatives in this case. The neuroprotective activity of the neuromodulator adenosine and its receptor, A1 receptor (A1R) in the central nervous system has been mentioned in different studies. Objective: We aimed to determine the anxiolytic, antidepressant and sedative effects of Japanese sake yeast as the first report. Method: Mice were subjected to a one-week stress protocol and concomitantly treated orally with sake yeast at the dose levels of 100, 200 and 300 mg kg-1 once daily for a week. The anxiolytic, antidepressant, and sedative actions of sake yeast were evaluated with the related tests. Results: In all dose regiments, sake yeast significantly improved functions in the EPM and FST. 200 and 300 mg/kg of sake yeast significantly increased sleep duration and reduced sleep latency. Anxiolytic and antidepressant-like activities of sake yeast were maintained by the injection of ZM241385 (15 mg kg−1), a selective adenosine A2AR antagonist but completely counteracted by the injection of 8-cyclopentyltheophylline (10 mg kg−1), a selective adenosine A1R antagonist. 300 mg/kg of the yeast significantly increased the BDNF levels. Amygdala corticosterone levels did not show any significant changes at any dosage. Amygdala TNF-α, IL-6 and IL-1β levels also decreased significantly with all the sake regiments compared to the control group. Conclusions: We conclude that oral sake yeast supplement exerts a neurobehavioral protective effect predominantly by activating central A1Rs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Standard phytochemical investigations were performed to identify the secondary metabolites in the methanol extract of Chaetocarpus castanocarpus bark (MECC) and investigate the neuropharmacological potential of MECC in Swiss albino mice. MATERIALS AND METHODS: Swiss albino mice were used in the forced swimming test (FST) and tail suspension test (TST) to evaluate the antidepressant effect of MECC. Also, the hole board test (HBT) and elevated plus maze (EPM) were conducted to examine anxiolytic activities. In contrast, the open field test (OFT) and hole cross test (HCT) were employed to evaluate sleeping disorders. RESULTS: Alkaloids, glycosides, flavonoids, terpenoids, coumarins, and tannins are only a few secondary metabolites identified in MECC by qualitative and quantitative phytochemical investigations. The oral administration of MECC considerably shortened the immobility duration during FST and TST. Encouraging dose-dependent anxiolytic effects were also observed in all relevant experiments compared to the control. Additionally, during the OFT and HCT assessment, a noteworthy decline in the locomotor activities of the experimental animals was observed. CONCLUSIONS: The results of this investigation suggest that the Chaetocarpus castanocarpus bark is a possible source of therapeutic candidates for treating neurological disorders. [ABSTRACT FROM AUTHOR]

Background: Conditions affecting the hypothalamic‐pituitary‐adrenal (HPA) axis are common in dogs. Testing the function of the HPA axis includes measurement of endogenous adrenocorticotropic hormone (eACTH) and performance of an adrenocorticotropic hormone (ACTH) stimulation test. Trazodone is commonly administered to dogs to decrease stress. In humans, trazodone significantly decreases plasma cortisol concentration via alpha‐1 adrenergic activity. Objectives: Determine the influence of trazodone on eACTH and serum cortisol concentrations in healthy dogs. Animals: Fourteen healthy, adult, companion dogs. Methods: Prospective, randomized placebo‐controlled study. Trazodone (8‐10 mg/kg) or placebo was administered PO 1 hour before eACTH measurement and ACTH stimulation testing. After a ≥7‐day wash‐out period, dogs received the opposite treatment. Differences in eACTH, pre‐ and post‐ACTH stimulation cortisol concentrations, and delta (difference between pre‐ and post‐ACTH) cortisol concentrations were analyzed using a paired t or signed‐rank test with a P <.05 significance level. Results: The eACTH concentrations were not significantly different (P =.23) between treatments. Similarly, no significant differences were found in the pre‐ACTH cortisol concentrations between treatments (P =.40). Post‐ACTH cortisol concentrations (P =.05) and delta cortisol concentrations (P =.04) were significantly lower when the dogs were treated with trazodone. Conclusions: Preliminary data suggest trazodone administration dampens the adrenocortical response to stimulation in healthy dogs. If similar effects are found in dogs with adrenal disease, the use of trazodone may affect diagnosis and clinical decision making in these populations. [ABSTRACT FROM AUTHOR]

This article examines the effectiveness of two medications, clomipramine and fluoxetine, in treating anxiety-related behaviors in dogs. The study concludes that both medications are effective in reducing symptoms of fear and anxiety, such as acral lick dermatitis and tail chasing. However, the article highlights the need to consider individual factors and clinical expertise when choosing a treatment for anxious behaviors in dogs. The text discusses three studies comparing the effectiveness of clomipramine and fluoxetine, which found that both medications were equally effective in reducing tail chasing and licking behavior. However, the studies had limitations, including small sample sizes and subjective owner reports, and did not address other potential causes of acral lick dermatitis. Further research is necessary to strengthen the evidence and address these limitations. [Extracted from the 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. [ABSTRACT FROM AUTHOR]

Two polyphenols–hyperoside (HYP) and protocatechuic acid (PCA) were reported to exert antidepressant activity in rodents after acute treatment. Our previous study also showed that this activity might have been influenced by the monoaminergic system and the upregulation of the brain-derived neurotropic factor (BDNF) level. A very long-term pharmacological therapy is required for the treatment of a patient with depression. The repetitive use of antidepressants is recognized to impact the brain structures responsible for regulating both emotional and cognitive behaviors. Thus, we investigated the antidepressant, anxiolytic, and procognitive effects of HYP and PCA in mice after acute and prolonged treatment (14 days). Both polyphenols induced an anxiogenic-like effect after acute treatment, whereas an anxiolytic effect occurred after repetitive administration. PCA and HYP showed procognitive effects when they were administered acutely and chronically, but it seems that their influence on long-term memory was stronger than on short-term memory. In addition, the preset study showed that the dose of 7.5 mg/kg of PCA and HYP was effective in counteracting the effects of co-administered scopolamine in the long-term memory impairment model induced by scopolamine. Our experiments revealed the compounds have no affinity for 5-HT1A and 5-HT2A receptors, whereas a significant increase in serum serotonin level after prolonged administration of PCA and HYP at a dose of 3.75 mg/kg was observed. Thus, it supports the involvement of the serotonergic system in the polyphenol mechanisms. These findings led us to hypothesize that the polyphenols isolated from Impatiens glandulifera can hold promise in treating mental disorders with cognitive dysfunction. Consequently, extended studies are necessary to delve into their pharmacological profile. [ABSTRACT FROM AUTHOR]

The common daisy (Bellis perennis) belongs to the family Asteraceae and, in recent years, some new research has been published on the bioactive compounds and biological activities of its extracts. In 2014, the knowledge was partially summarized, but several new studies have been published in the last nine years. In addition, the substances were tabularly consolidated to give a comprehensive overview of over 310 individual components, compound classes, and bioactivities, as well as their accurate plant organ origin. The latest results have shown that the plant has antioxidative, antimicrobial, anticancerogenic, wound healing, antidepressive, anxiolytic, nephroprotective, and insulin mimetic effects, as well as an effect on lipid metabolism. Some studies in the field of homeopathy were also listed. Ideally, a biological effect and one or several compound(s) can be correlated. However, the compounds of the extracts used have often been qualified and quantified, but it remains unclear which of these substances have an activity. The works often stick at the level of the crude extract or a fraction, but not at a single purified and tested compound and, consequently, they are hampered by a missing comprehensive bioactivity workflow. This review provides a critical overview and gaps and offers a basis for further research in this area. [ABSTRACT FROM AUTHOR]

Background and Aim: Despite the plethora of drugs currently available, neurodegenerative diseases are leading cause of morbidity and mortality globally. Hence, there is a need for the development of more alternatives that are safe, efficient, and effective. In Nigeria, the leaves of Cnidoscolus aconitifolius are used ethnomedicinally for the management of central nervous system related disorders such as convulsion and anxiety. In this study, we evaluated some neuropharmacological effects of the methanol leaf extract of C. aconitifolius (CAE) in mice. Methods: Different groups of mice (n = 5) were administered 100, 200 and 400 mg/kg of CAE and then evaluated for sedative-hypnotic, anxiolytic, antidepressant, anticonvulsant, and muscle relaxant properties using standard protocols. Results: The onset of sleep was significantly reduced (P < 0.001), and sleep duration was significantly (P < 0.01) prolonged at doses of 200 and 400 mg/kg. All doses of the extract significantly (P < 0.05) reduced the number of head dips in hole-board test. In elevated plus maze test, the dose of 400 mg/kg increased (P < 0.05) the number of open arm entries without altering the time spent in the open arms of the maze. At 400 mg/kg, there was a significant (P < 0.05) reduction in the duration of immobility in forced swimming test. Doses of 200 and 400 mg/kg of the extract reduced (P < 0.05) the duration of immobility in the tail suspension test. The extract did not exhibit any anticonvulsant effect either in chemically induced or electrically induced models, and there was no significant alteration in motor coordination in extract-treated mice. Conclusion: Our results showed that CAE possesses sedative-hypnotic and antidepressant properties but lack anticonvulsant, anxiolytic and muscle relaxant actions in mice.

PICO Question In dogs with anxious behaviours, is fluoxetine more effective than clomipramine in reducing anxiety-related behaviours? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three controlled studies were critically appraised. Strength of evidence Moderate. Outcomes reported Administration of either fluoxetine or clomipramine to adult dogs reduces symptoms of fear and anxiety. Conclusion Both fluoxetine and clomipramine are effective in reducing acral lick dermatitis and tail chasing behaviours, but there is no evidence that one drug is more effective than the other. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Background: Clinically significant psychoautonomous syndrome, along with other modifiable factors (obesity, dyslipidemia, low physical activity, smoking, arterial hypertension, etc.) increases the risk of development and progression of coronary artery disease (CAD). In particular, patients who have undergone coronary interventions and have a higher anxiety level are prone to the development of CAD complications. Aim: To characterize the basal parameters of clinically significant psychoautonomous syndrome and their changes over time under combination therapy, including anxiolytics, at various stages of rehabilitation of the patients after endovascular myocardial revascularization. Materials and methods: This open-label randomized controlled prospective study included 60 patients aged 45 to 75 years admitted to our in-patient department for rehabilitation treatment after coronary stent placement. The patients from the intervention group (n = 30), in addition to basic treatment for CAD, were administered anxiolytic therapy (alimemazine tartrate at daily dose of 12.5 to 25 mg i. m. at the early rehabilitation step and at 5 to 10 mg during their out-patient follow-up). The in-patient study period included 3 study visits (at admittance, i. e., Day 1, at Days 5 or 6, and at discharge at Day 10 to 14). Two further study visits were performed during the out-patient rehabilitation period at Days 30 and 60. At each visit, the emotional state, sleep quality, subjective signs of autonomous dysregulation, autonomous background and suprasegmental vegetative regulation, including temporal and spectral indicators of heart rate variability, were evaluated. Results: After endovascular myocardial revascularization (the in-patient study period, Day 1) patients of the intervention and control groups (n = 30 in both groups) demonstrated comparable moderate levels of state anxiety (median [Q1; Q3]: 42 [40; 46] and 42 [36; 43], respectively) and trait anxiety (45 [41; 48] and 42 [40; 46], associated with insomnia (PSQI score: 8 [6; 12] and 6 [3; 9]) and autonomous imbalance (SDNN: 73 [61; 89] and 70 [44; 95]) with a shift to sympathetic hyperactivity. Addition of an anxiolytic initiated the regression of psychoautonomous abnormalities already by the end of the early in-patient rehabilitation period) (Days 10 to 14), with a subsequent decrease in state anxiety to 36 [33; 39] and trait anxiety to 33 [32; 37] (p 0.001), regression of insomnia according to PSQI to 2 [2; 4] (p 0.001), and an improvement of autonomous balance (SDNN) to 113 [81; 132] (p 0.001) at days 45 to 60 of the outpatient follow-up. The only adverse event in the patients receiving the treatment for psychoautonomous dysfunction was increased sleepiness at daytime, which was registered in most of them at initiation of the therapy for 2 to 3 days and did not require any dose modification. There were no other clinically significant adverse events, including cardiovascular. Conclusion: Patients with an increased level of anxiety after endovascular myocardial revascularization are characterized by an autonomous imbalance with sympathetic hyperactivity. Addition of an anxiolytic to the basic treatment for CAD allows for a reduction of both components of the psychoautonomous syndrome, which may be an additional factor for successful patient rehabilitation and as a consequence for the prevention of CAD progression.

Due to the health benefits of polyphenols and dietary fiber in combating mental disorders, we hypothesized that a polyphenol- and dietary fiber-enriched soup (RJ6601) would improve mental wellness in a rat model of middle-aged women. To test this hypothesis, female Wistar rats aged 18 months (350–450 g) were orally administered RJ6601 at doses of 200 and 400 mg/kg BW for 28 days. The anxiolytic, antidepression, and memory-enhancing effects were assessed every 7 days throughout the study period. The neuron density and levels of activities of AChE, total MAO, MAO-A, MAO-B, MDA, SOD, CAT, GSH-Px, IL-1β, IL-6, and BDNF in the prefrontal cortex at the end of study were also investigated. Furthermore, the amounts of Lactobacillus spp. and Bifidobacterium spp. in their feces were also determined. The results revealed that the developed soup shows anxiolytic, antidepression, and memory-enhancing effects. An increased neuron density; reductions in AChE, total MAO, MAO-A, MAO-B, and MDA; and an elevation of serum BDNF, together with increased amounts of both bacterial species in feces, were also observed. Our results suggest that RJ6601 is a potential mental wellness promotion supplement that enhances BDNF levels, brain plasticity, neurotransmitter balance, and oxidative stress and inflammation status, along with improving microbiota.

Byttneria pilosa, a flowering plant from the Malvaceae family traditionally used to treat ailments such as boils and scabies, is here investigated for its potential health benefits. The study focused on evaluating its antioxidant and antidiabetic properties in vitro, as well as the in vivo anxiolytic and antidepressant activities of the methanol extract of B. pilosa leaf (MEBP). The study employed various assays to evaluate antioxidant activity, including 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, reducing power capacity, and quantification of the total phenolic and flavonoid contents of MEBP. Additionally, anxiolytic and antidepressant activities were evaluated through four tests: elevated plus-maze test (EPMT), light–dark box test (LDBT), forced swimming test (FST), and tail suspension test (TST). Antidiabetic effect was determined using α-amylase inhibition assay. Docking analysis was performed using BIOVIA and Schrödinger Maestro (v11.1), and the absorption, distribution, metabolism, and excretion/toxicity (ADME/T) properties of bioactive substances were investigated using a web-based technique. MEBP exhibited moderate antioxidant activity in DPPH radical scavenging and reducing power capacity assays, with a dose-dependent response. The total phenolic and flavonoid contents measured were 70 ± 1.53 mg and 22.33 ± 1.20 mg, respectively. MEBP demonstrated significant effects in α-amylase inhibition comparable to acarbose. In behavioral tests, MEBP dose-dependently altered time spent in open arms/light box and closed arms/dark box, indicating anxiolytic effects. Moreover, MEBP significantly reduced immobility duration in FST and TST, suggesting antidepressant properties. Molecular docking analysis revealed favorable interactions between beta-sitosterol and specific targets, suggesting the potential mediation of anxiolytic and antidiabetic effects. Overall, MEBP exhibits notable anxiolytic and antidepressant properties, along with moderate antioxidant and antidiabetic activities.

Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense, Spatholobus suberectus, etc. Studies have proved that formononetin has good anti-inflammatory, antitumor, antioxidant, antidepressant, anxiolytic and other pharmaco- logical effects. This paper summarizes the pharmacological action and molecular mechanism of formononetin, in order to provide a theoretical basis for the development and clinical application of formononetin. [ABSTRACT FROM AUTHOR]

Sembung rambat (Mikania micrantha Kunth) is a weed that grows easily and may hinder cultivation of plants. However, it also has medicinal benefits. M. micrantha contains various secondary compounds such as linalool, quercetin, a-terpinene, and terpinene-4-ol, which have anti-depressant effects. To our knowledge, no studies have been conducted on the anxiolytic and anti-depressant activities of the leaves of this plant. This study determined the anxiolytic and anti-depressant activities of the ethanol extract of M.micrantha Kunth leaves. 48 male Swiss-Webster mice were assigned into four groups. All extracts, control, and Amitriptylilne groups were administered the same treatment. The forced swimming test (FST) and tail suspension test (TST) were carried out to examine anti-depressant activity, whereas the elevated plus maze test (EPM) was used to assess anxiolytic activity. The FST and TST data showed that immobility times were significantly reduced when M. micrantha Kunth was administered at 250 mg/kg and 500 mg/kg doses (p<0.001, p<0.05, p<0.012, and p<0.033, respectively), while 250 mg/kg of M. micrantha Kunth increased the time spent in the open arms against the control group, although it was slightly lower than the amitriptyline group (p < 0.05). There were no significant differences in the open-arm entries within the groups. M. micrantha Kunth leaves ethanol extract reduces the immobility time in FST and TST with increased entries on open arms and time spent in EPM. [ABSTRACT FROM AUTHOR]

The investigation of monoterpenes as natural products has gained significant attention in the search for new pharmacological agents due to their ability to exhibit a wide range in biological activities, including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, and vasodilating properties. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing effects in experimental dementia and Parkinson's disease. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive avenue within experimental pharmacology, offering a promising approach for the therapy of diverse pathological conditions. Biologically active substances such as monoterpenes, for example, borneol, camphor, geraniol, pinene, and thymol, are used to synthesize compounds with analgesic, anti-inflammatory, anticonvulsive, antidepressant, anti-Alzheimer's, antiparkinsonian, antiviral and antibacterial (antituberculosis) properties. Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, the conjugation of myrtenal with the established pharmacophore adamantane enables the augmentation of several of its pivotal properties. Myrtenal–adamantane derivatives exhibited a variety of beneficial characteristics, such as antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective properties, which are worth examining in more detail and at length. [ABSTRACT FROM AUTHOR]

Purpose of Review: Benzodiazepines, due to their anxiolytic properties, are prescribed to reduce anxiety and insomnia. They might have hypotensive effect via potentiation of the inhibitory effect of gamma-amino butyric acid (GABA) in the central nervous system and vasodilatory properties. However, studies comparing the effect of benzodiazepines in lowering blood pressure (BP) are equivocal. This systematic review and meta-analysis was planned to assess the efficacy of benzodiazepines in reducing blood pressure in short term among hypertensive patients. Recent Findings: Various trials and retrospective analysis conducted previously have reported that benzodiazepines cause short- as well as long-term BP reduction in patients with increased anxiety with hypertension. On the other hand, several studies investigating the efficacy of benzodiazepines in patients with hypertension have reported inconclusive results. The primary question about the effect of benzodiazepines in lowering BP remains unanswered. Summary: In this meta-analysis of seven studies, benzodiazepines were found comparable to standard drugs in reducing systolic and diastolic BP in patients having hypertension. Although, the mean difference in systolic BP with benzodiazepines and placebo was statistically not significant, the difference can be considered as clinically meaningful. The current review offers preliminary evidence that benzodiazepines may have antihypertensive properties and may be used as add-on antihypertensive in a subset of patients in short term. The existing data are encouraging, but more clinical trials and mechanistic research are required to ascertain the long-term benefits. [ABSTRACT FROM AUTHOR]

Aims: This review aimed to comprehensively examine kratom's therapeutic potential for treatment of mental health-related issues as well as any related benefits and risks. Design: Systematic review. Data sources: Google Scholar, Web of Science, PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, and Medline. Review methods: Three authors carried out electronic search of articles published between 1950 to September 2022 through major databases for a duration of three months (from July to September 2022). Each author independently screened the literature for inclusion and exclusion criteria, the findings were then compared, discrepancies between authors were resolved, and the final selection of articles were reviewed. Results: A total of 46 articles were included in this review. A total of three in vitro and animal studies and five cross-sectional online surveys reported the therapeutic potential of kratom in opioid replacement therapy. In addition, a total of two animal studies and three cross-sectional online surveys highlighted the role of kratom as a potential antidepressant and anxiolytic. Contrastingly, two animal studies, 11 studies in human subjects, and 16 case reports documented the risk of kratom dependence, cravings, tolerance, and kratom-related substance use disorder as the major safety concern of implementing kratom use as a therapeutic agent. Conclusion and impact: In the absence of human clinical trial, coupled with various considerable adverse events of kratom (not limited to psychological side effects), evidence to support kratom as potential therapeutic use remains inconclusive. [ABSTRACT FROM AUTHOR]

Objective: This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods: This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results: G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion: In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials. [ABSTRACT FROM AUTHOR]

Previous pharmacological data have shown the possible existence of functional interactions between μ- (MOP), κ- (KOP), and δ-opioid receptors (DOP) in pain and mood disorders. We previously reported that MOP knockout (KO) mice exhibit a lower stress response compared with wildtype (WT) mice. Moreover, DOP agonists have been shown to exert antidepressant-like effects in numerous animal models. In the present study, the tail suspension test (TST) and forced swim test (FST) were used to examine the roles of MOP and DOP in behavioral despair. MOP-KO mice and WT mice were treated with KNT-127 (10 mg/kg), a selective DOP agonist. The results indicated a significant decrease in immobility time in the KNT-127 group compared with the saline group in all genotypes in both tests. In the saline groups, immobility time significantly decreased in MOP-KO mice compared with WT mice in both tests. In female MOP-KO mice, KNT-127 significantly decreased immobility time in the TST compared with WT mice. In male MOP-KO mice, however, no genotypic differences were found in the TST after either KNT-127 or saline treatment. Thus, at least in the FST and TST, the activation of DOP and absence of MOP had additive effects in reducing measures of behavioral despair, suggesting that effects on this behavior by DOP activation occur independently of MOP.

The lateral hypothalamus' orexinergic system has been associated with anxiety-related behaviors, and electroacupuncture (EA) modifies orexin neurons to control the anti-anxiety process. However, in a rat model of post-traumatic stress disorder (PTSD), the important role of LH orexin neurons (OXNs) in the anxiolytic effects induced by EA has not been explored. In this study, rats underwent modified single prolonged stress (MSPS) for seven days before developing EA. The rats were then subjected to elevated plus maze (EPM) and open field (OFT) tests, and western blot and c-Fos/orexin double labeling investigations were carried out to determine the functional activation of LH orexinergic neurons. Compared to MSPS model rats, it has been demonstrated that EA stimulation enhanced the amount of time spent in the central zone (TSCZ) in OFT and the amount of time spent in the open arm (TSOA) in EPM in MSPS model rats (P

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography–mass spectrometry (GC–MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1–50 mg/kg p.o.) and DHS (0.1–10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1–50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS. [ABSTRACT FROM AUTHOR]

Background: Ketamine may be effective in treating symptoms of anxiety, but the time profile of ketamine's anxiolytic effect is ill-defined. This systematic review and meta-analysis investigated the anxiolytic effect of ketamine at different time points across a range of clinical settings. Methods: Electronic databases were searched to capture randomised control trials measuring the anxiolytic effects of ketamine in contexts including mood disorders, anxiety disorders and chronic pain. Meta-analyses were conducted using a random-effects model. The correlations between (1) improvements in mean anxiety and depression scores, and (2) peak dissociation and improvements in mean anxiety scores were also assessed. Results: In all, 14 studies met inclusion criteria. Risk of bias was high in 11 studies. Ketamine significantly reduced anxiety scores compared to placebo at acute (<12 h; standard mean difference (SMD): −1.17, 95% confidence interval (CI) [−1.89, −0.44], p < 0.01), subacute (24 h; SMD: −0.44, 95% CI [−0.65, −0.22], p < 0.01) and sustained (7–14 days; SMD: −0.40, 95% CI [−0.63, −0.17], p < 0.01) time points. Exploratory analyses revealed improvements in anxiety and depression symptoms correlated at both subacute (R 2 = 0.621, p = 0.035) and sustained time points (R 2 = 0.773, p = 0.021). The relationship between peak dissociation and improvement in anxiety was not significant. Conclusions: Ketamine appears to offer rapid and sustained anxiety symptom relief across a range of clinical settings, with anxiolytic effects occurring within the first 12 h of administration and remaining effective for 1–2 weeks. Future studies could explore the effects of ketamine maintenance therapy on anxiety symptoms. [ABSTRACT FROM AUTHOR]

Purpose: To determine the association between age and retinal full-field electroretinographic (ERG) measures in companion (pet) dogs, an important translational model species for human neurologic aging. Methods: Healthy adult dogs with no significant ophthalmic abnormalities were included. Unilateral full-field light- and dark-adapted electroretinography was performed using a handheld device, with mydriasis and topical anaesthesia. Partial least squares effect screening analysis was performed to determine the effect of age, sex, body weight and use of anxiolytic medication on log-transformed ERG peak times and amplitudes; age and anxiolytic usage had significant effects on multiple ERG outcomes. Mixed model analysis was performed on data from dogs not receiving anxiolytic medications. Results: In dogs not receiving anxiolytics, median age was 118 months (interquartile range 72–140 months, n = 77, 44 purebred, 33 mixed breed dogs). Age was significantly associated with prolonged peak times of a-waves (dark-adapted 3 and 10 cds/m2 flash p < 0.0001) and b-waves (cone flicker p = 0.03, dark-adapted 0.01 cds/m2 flash p = 0.001). Age was also significantly associated with reduced amplitudes of a-waves (dark-adapted 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.005) and b-waves (light-adapted 3 cds/m2 flash p < 0.0001, dark-adapted 0.01 cds/m2 flash p = 0.0004, 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.007) and flicker (light-adapted 30 Hz 3 cds/m2p = 0.0004). Within the Golden Retriever breed, these trends were matched in a cross-sectional analysis of 6 individuals that received no anxiolytic medication. Conclusions: Aged companion dogs have slower and reduced amplitude responses in both rod- and cone-mediated ERG. Consideration of anxiolytic medication use should be made when conducting ERG studies in dogs. [ABSTRACT FROM AUTHOR]

Background: The classical ayurvedic formulation Bru-satavari after consumption by people can get a restful night's sleep and feel rejuvenated. The goal of this study is to look at important phytoconstituents which may influence the neuropharmacological activities. Therefore, we made an effort to learn the methanol extract of classical ayurvedic formulation Bru-Satabari having anyneuropharmacological activity. Materials and Methods: The open field, hole cross, rota-rod, and thiopental sodium-induced sleeping duration tests on mice were used to examine the sedative effect of brusatavari at dosages of 400 mg/kg. The anxiety-relieving effect evaluated using the hole-board test. Compared to the positive control drug diazepam, sedative and anxiolytic effects were seen. Analgesic effect was evaluated by tail flick method. Results: According to the study, the extract has remarkable neuropharmacological action because it lowers mice's anxiety and locomotor activity in all instances of hole cross, open field, and rota rot tests when compared to the control. Additionally, compared to the standard and control group, the extract extends sleep time with a rapid onset of effect. Further the Bru-satavari exhibited excellent analgesic activity in comparison to control. Conclusion: The findings confirm the use of Bru-Satabari in traditional medicine by showing that it exhibits sedative and anxiolytic properties. Best suggested: More research into the drug's mechanism of action and the isolation of its active compounds. [ABSTRACT FROM AUTHOR]

Arthritis is an inflammatory disease that affects the joints. Patients suffering from chronic pain are anxious, which contributes to reducing the quality of life. The development of analgesic compounds with anxiolytic properties could prove to be of great interest for the treatment of chronic pain. The objective of the present study was to evaluate the analgesic and anxiolytic properties of the aqueous extract of the bark of the trunk of Diospyros mespiliformis in arthritic mice. Arthritis was induced by injection of 1% formaline into the left hind paw of the animals. Inflammatory pain and comorbid anxiety were tested using a hotplate (55 ± 0.5 °C) and labyrinths (Dark and Light and the open arena), respectively. The aqueous extract of Diospyros mespiliformis reduced the inflammatory process by inhibiting the edema of the legs of animals to a maximum percentage of 63.63 % (minimum of 8.82%) as well as the significant increase (p < 0.001) of the threshold of nociception at the dose of 100 mg/kg. A significant increase (p < 0.001) in the time spent in the lighted compartment alongside the decrease in the time spent in the dark environment was observed with the two-compartment maze. In the open arena the time spent in the central plaza significantly (p < 0.001) increased compared to the time spent on the edge. In addition, a significant decrease (p < 0.01) in the frequency of grooming and training was observed. The aqueous extract of the bark of the trunk of Diospyros mespiliformis displayed beneficial effects on pain and anxiety, justifying it traditional use for the management of arthritis. [ABSTRACT FROM AUTHOR]

In folklore medicine, Conocarpus lancifolius is used to treat various illnesses. The main objective of this study was a comprehensive investigation of Conocarpus lancifolius leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 ± 0.15 µg GAE/mg) and flavonoids (47.54 ± 0.45 µg QE/mg) with stronger antiradical effects through DPPH (IC50 = 16.66 ± 0.42 µg/mL), TAC (77.33 ± 0.41 µg AAE/mg) and TRP (79.11 ± 0.67 µg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC50 = 110.13 ± 1.71 µg/mL) activity through a modified Ellman's method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest. [ABSTRACT FROM AUTHOR]