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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]

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

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.

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]

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.

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]

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: 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]

Analyzing sleep electroencephalography (EEG) data can provide insights from application of basic principles of signal analysis (filtering, sampling, and spectral processing). This study investigated whether jasmine essential oil (JEO) intake differed in sleep EEG patterns from sedative drug intake. Adult male Swiss Albino (ICR) mice treated with distilled water, jasmine essential oil and lorazepam administration were assessed for sleep stages offline from the dorsal hippocampal brain activity. Two-way repeated measures ANOVA revealed that JEO reduced the wakening duration while increasing NREM sleep following 60 minutes of intake to the end of the 3-hour recording, in comparison to water gavage. Their pharmaco-EEG fingerprints after a single intake of jasmine oil and lorazepam showed a high power-level of delta and beta frequencies in the first 30 minutes of recording. A dramatic decrease in gamma2 power activity was observed only after lorazepam was administered. Slow wave activity within the hippocampus was a highlight of the scent relaxant as promoter of non-REM sleep.

Abstract Background Citrus maxima (Burm.) Merr. is traditionally used for its diverse pharmacological properties. Therefore, there remains a possibility that the seed extract may contain some bioactive compounds. The present study was carried out to evaluate the anxiolytic, analgesic, and anti-inflammatory effects of methanolic seed extract of Citrus maxima (MECM). Method The effect of MECM on the rodent central nervous system was evaluated using the hole-board and elevated plus-maze method. Analgesic effect was measured with the acetic acid-induced writhing and formalin-induced paw licking method. The anti-inflammatory effect was examined using a formalin and carrageenan-induced mice paw edema model. Results The MECM at doses of 200 mg/kg and 400 mg/kg significantly (p

Primary dermatological disorders which are frequently exacerbated by stress and whose course is affected by the psychological state of the patient are called psychophysiologic or psychosomatic diseases. Psychosocial stress plays a major role in the onset and/or aggravation of these skin diseases. A close relationship between the skin and the mind mediated via hormones and neurotransmitters and altered cutaneous permeability barrier homeostasis by psychological stress constitute the basic psychopathology. The common skin conditions precipitated/aggravated by stress include psoriasis, vitiligo, atopic dermatitis, acne vulgaris, alopecia areata, urticaria, lichen planus, prurigo, seborrheic dermatitis, and hyperhidrosis. These cutaneous diseases often have a chronic, unpredictable course with multiple remissions and relapses leading to significant psychiatric morbidity, and disease-related stress further acts as an aggravating factor for the cutaneous disease leading to a vicious cycle. Increased awareness about these psychophysiologic diseases among dermatologists has helped to incorporate psychotherapeutic treatment in the form of psychotropic drugs and nonpharmacological interventions in the management of these patients. A multidisciplinary approach consisting of dermatologists along with psychiatrists and psychologists in a liaison framework has proven useful for these patients.

Aim: We aimed to develop a decision aid (DA) for individuals with anxiety disorders who consider tapering benzodiazepine (BZD) anxiolytics, and if tapering, tapering BZD anxiolytics with or without cognitive behavioral therapy (CBT) for anxiety. We also assessed its acceptability among stakeholders. Methods: First, we conducted a literature review regarding anxiety disorders to determine treatment options. We cited the results of the systematic review and meta-analysis, which we conducted previously, to describe the related outcomes of two options: tapering BZD anxiolytics with CBT and tapering BZD anxiolytics without CBT. Second, we developed a DA prototype in accordance with the International Patient Decision Aid Standards. We carried out a mixed methods survey to assess the acceptability among stakeholders including those with anxiety disorders and healthcare providers. Results: Our DA provided information such as explanation of anxiety disorders, options of tapering or not tapering BZD anxiolytics (if tapering, the options of tapering BZD anxiolytics with or without CBT) for anxiety disorder, benefits and risks of each option, and a worksheet for value clarification. For patients (n=21), the DA appeared to be acceptable language (86%), adequate information (81%), and well-balanced presentation (86%). The developed DA was also acceptable for healthcare providers (n=10). Conclusion: We successfully created a DA for individuals with anxiety disorders who consider tapering BZD anxiolytics, which was acceptable for both patients and healthcare providers. Our DA was designed to assist patients and healthcare providers to involve decision-making about whether to taper BZD anxiolytics or not. [ABSTRACT FROM AUTHOR]

The roots of Withania somnifera (L) Dunal (W. somnifera) are used extensively in Ayurveda, the classical Indian system of medicine, and W. somnifera is categorized as a rasayana, which are used to promote physical and mental health, to provide defense against disease and adverse environmental factors and to arrest the aging process. W. somnifera has been used to stabilize mood in patients with behavioural disturbances. The objective of this study was to investigate pharmacognostical, phytochemical features and anxiolytic activity of alcoholic extracts of W. somnifera roots. The various pharmacognostical variables were assessed using generally accepted techniques with certain variations. An established test technique that is documented in the literature was used to determine the qualitative analysis of different phytochemical elements. The anxiolytic efficacy of the alcoholic extract of W. somnifera roots in mice was evaluated using the elevated plus maze test (EPMT), light and dark test (L and DT), and open field test (OFT). Extract dosages of 250, 500, and 750 mg/kg were compared to the recommended dosage of diazepam (1 mg/kg) to determine its efficacy. Alcoholic extract underwent phytochemical examination, which identified the presence of fixed oils, lipids, proteins, amino acids, carbohydrates, tannins, and phenolics. The percentage of time spent and the number of entries in the open arm in EPMT were both considerably enhanced by the alcoholic extract of W. somnifera roots (250, 500, 750mg/kg, p.o.). The extract significantly increased time spent, the frequency of crossings, and decreased the length of immobility in the light box in L and DT. The extract in OFT significantly increased the number of rearings, increased ambulation, and decreased selfgrooming and faecal dropping all signs of exploratory behaviour. The findings of the current investigation provide scientific support for the traditional use of W. somnifera by indicating that an alcoholic extract of its roots may have anxiolytic properties. [ABSTRACT FROM AUTHOR]

Species belonging to the genus Lippia are used worldwide as foods, beverages, and seasonings. Studies have demonstrated that these species have antioxidant, sedative, analgesic, anti-inflammatory, and antipyretic activities. This work aimed to evaluate the antibacterial activity and anxiolytic effect by different pathways of essential oils and ethanolic extracts of three species of Lippia (Lippia alba, Lippia sidoides, and Lippia gracilis). The ethanolic extracts were characterized by HPLC-DAD-ESI-MSn and their phenolics were quantified. The antibacterial activity was evaluated by determining the minimal inhibitory concentration and modulation of antibiotic activity, and toxic and anxiolytic effects were evaluated in the zebrafish model. The extracts showed compositions with a low ratio and shared compounds. L. alba and L. gracilis showed higher amounts of phenols and flavonoids, respectively. All extracts and essential oils presented antibacterial activity, especially those obtained from L. sidoides. On the other hand, L. alba extract presented the most significant antibiotic-enhancing effect. The samples were not toxic after 96 h of exposure, but showed an anxiolytic effect through modulation of the GABAA receptor, while L. alba extract acted via modulation of the 5-HT receptor. This new pharmacological evidence opens horizons for therapeutic approaches targeting anxiolytic and antibacterial therapies and food conservation using these species and their constituents. [ABSTRACT FROM AUTHOR]

Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Neurada procumbens Linn. possesses a wide range of phytochemical and bioactive entities such as flavonoids and polyphenols that decrease the oxidative stress and enhance synaptic plasticity, resulting in accelerated healing processes. Almost all parts of the plant have been used in the traditional system of medicine for various disorders including its use as an anticonvulsant, sexual tonic, and anti-rheumatic agent. This study is designed to evaluate the anxiolytic and antidepressant activities of the methanolic crude extract of N. procumbens (Np.Cr) based on its use in traditional medicine and presence of the phytochemical constituents. Aqueous methanolic extract of Np.Cr was prepared under reduced pressure using rotary evaporator, and different chemical constituents were identified by phytochemical screening. Light/dark exploration, elevated plus maze (EPM), and hole board tests were used to assess the anxiolytic activity, while forced swim and tail suspension tests were used to assess the antidepressant potential of the crude extract. Treatment groups treated individually with 3 different doses; i.e., 50, 100, and 200 mg/kg of Np.Cr, showed a dose-dependent increase in time spent in light compartment and in open arms as well as increased number of head poking by the experimental animals. Np.Cr showed significant antidepressant potential (P <.05) as evident from marked decrease in behavioral despair. Findings of the present study assure that N. procumbens possess significant anxiolytic and antidepressant potential with the demands of further investigations to identify the active compound(s) responsible for these pharmacological effects. Graphical Abstract [ABSTRACT FROM AUTHOR]

Lavender essential oil is economically important and widely used in aromatherapy perfumery, food industry and pharmacy. Bulgaria is a global leader in lavender cultivation overtaking countries such as France, UK, China, India, and Spain during the last few years. The aim of this research is: 1) to characterize a lavender essential oil sample obtained from agricultural plantation near Pomorie, Bulgaria; 2) to perform descriptive statistical test based on a data set of 13 samples available in 4 publications, 3) to compare the varieties regarding the quantity of the most important components such as linalool and linalyl acetate 4) to summarize the pharmacological effects of the main components. As a result of GS/MS analysis of the essential oil sample obtained from agricultural plantation near Pomorie, we identified 44 compounds. The major constituents were linalyl acetate (27.5%) linalool (24.1%), E-β-ocimene (7.0%), terpinen-4-ol (5.1%) caryophyllene (4.5%), carvacrol (4.4%), lavandulyl acetate (3.5%), Z-β-farnesene (3.3%), and -Z-β-ocimene (3.2%). Linalool and linalyl acetate are the main ingredients based on which the quality of the essential oil is evaluated. In the studied samples they fluctuated between varieties depending on the year of extraction and the locations of origin in Bulgaria. Some varieties were characterized by a more stable ratio of linalool – linalyl acetate, compared to others. The main other components of our sample as well as the other examined Bulgarian samples fit the standards according to the requirements of ISO (2002) and the of European Pharmacopoeia (10th edn., Council of Europe 2020) with few exceptions. Lavender oil has numerous pharmacological applications based on its anxiolytic, sedative, antioxidant, anti-inflammatory, antitumor and antimicrobial activities. Although linalool and linalyl acetate largely contribute to these effects, the overall efficacy of lavender oil is proven to be due synergistic relationships between the components. [ABSTRACT FROM AUTHOR]

Abstract Ortho-eugenol is a synthetic derivative from eugenol, the major compound of clove essential oil, which has demonstrated antidepressant and antinociceptive effects in pioneering studies. Additionally, its effects appear to be dependent on the noradrenergic and dopaminergic systems. Depression and anxiety disorders are known to share a great overlap in their pathophysiology, and many drugs are effective in the treatment of both diseases. Furthermore, high levels of anxiety are related to working memory deficits and increased oxidative stress. Thus, in this study we investigated the effects of acute treatment of ortho-eugenol, at 50, 75 and 100 mg/kg, on anxiety, working memory and oxidative stress in male Swiss mice. Our results show that the 100 mg/kg dose increased the number of head-dips and reduced the latency in the hole-board test. The 50 mg/kg dose reduced malondialdehyde levels in the prefrontal cortex and the number of Y-maze entries compared to the MK-801-induced hyperlocomotion group. All doses reduced nitrite levels in the hippocampus. It was also possible to assess a statistical correlation between the reduction of oxidative stress and hyperlocomotion after the administration of ortho-eugenol. However, acute treatment was not able to prevent working memory deficits. Therefore, the present study shows that ortho-eugenol has an anxiolytic and antioxidant effect, and was able to prevent substance-induced hyperlocomotion. Our results contribute to the elucidation of the pharmacological profile of ortho-eugenol, as well as to direct further studies that seek to investigate its possible clinical applications.

Absract: Drymaria cordata subsp. diandra (Sw.) J.A. Duke is one of the most important medicinal plants used by various tribes throughout India and the world. It is a traditional herbal medication that is used to treat peptic ulcers, female sterility, headaches, glomerulonephritis, sleeping problems, convulsions, and febrile illnesses in children as an ingredient in many local poly herbal formulations, as well as other major or minor ailments such as cold, headache, coryza, bronchitis, leprosy, tumors, and so on. The plant has been shown to contain a variety of secondary plant metabolites such as alkaloids, flavonoids, tannins, saponins, phenols, and terpenoids which have been proved to show Anti-bacterial, analgesic and anti-pyretic, anti-tussive, anxiolytic, anti-oxidant, anti-diabetic, sinusitis and cytotoxic activities. All the records associated with this plant was accrued from distinctive treatise including reference books, and databases like PubMed, Science Direct, Scopus, Web of Science, Google Scholar, Researchgate, Publons etc. The goal of this paper is to give an outline and critical analysis of the stated traditional uses, anatomy, phytochemistry, pharmacological actions, and toxicology studies of D. cordata, as well as to find the remaining holes and provide a base for further research. The review also tries to get people and academics interested in the wide range of medicinal qualities of the plant so that it can be used better in the future.

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.

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.

PICO question In hospitalised dogs or dogs confined postsurgery, does administration of trazodone reduce stress related behaviours compared to no treatment with trazodone? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three papers were critically reviewed. One was a prospective, randomised, blinded observational study, another was a randomised, placebo-controlled clinical trial, and the last was a non-randomised prospective, open-label clinical trial. Strength of evidence Weak. Outcomes reported The administration of trazodone to hospitalised dogs reduced several observed stress related behaviours compared to a control group that was environmentally matched to the treatment group (Gilbert-Gregory et al., 2016). In dogs subjected to postsurgical confinement at home, trazodone administration was not more effective at reducing stress related behaviours compared with a placebo in one study (Gruen et al., 2017); however, it was effective when observed in a non-placebo controlled clinical trial (Gruen et al., 2014). Further investigation with a larger sample size would assist in strengthening the evidence of an association between trazodone administration and a reduction in the behavioural signs of stress in dogs. Conclusion The available evidence weakly supports the hypothesis that administration of trazodone is an effective treatment in reducing stress related behaviours in hospitalised dogs and dogs confined post-surgery, and further studies are required to confirm its efficacy. The quality of the evidence when hospitalised dogs was studied was moderate (Gilbert-Gregory et al., 2016), however in dogs studied that were confined postsurgery, the evidence is weaker (Gruen et al., 2014; Gruen et al., 2017). Different trazodone doses were evaluated in the studies and so further studies focusing on dose effects are required to determine appropriate dose rates. Further studies also need to be conducted to evaluate the appropriate length of time that trazodone should be given prior to a stressful event, as well as whether trazodone needs to be used in conjunction with other anxiolytic drugs to optimise efficacy. 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.

The case of a 42-year-old female patient with pronounced itching and exanthema, mainly in the area of the trunk and lower limbs, is presented. Previously, the patient took antihistamines without effect, was treated for scabies, but the itching remained pronounced and led to rash and excoriations. From the anamnesis, it was found that the patient has a high level of stress. According to the Hospital Anxiety and Depression Scale, the anxiety of the patient reached 14 points, and depression 1 point. Functional (psychogenic) itching was suspected. Since the patient refused dermatologist consultation, therapy with the anxiolytic temgicoluril, topical antipruritic agents and nonpharmacological methods of treatment were recommended at the initial stage. The patient felt a significant relief of itching symptoms on the first day of anxiolytic usage, she withdrew topical antipruritic agents after 5 days of anxiolytic treatment, in 15 days she began to reduce the dose of temgicoluril, and at the end of the third week she stopped treatment with anxiolytic due to a significant positive effect. In three weeks, practically all elements of the rash, except for the largest wounds from scratching, disappeared. The peculiarity of the case is that functional itching was completely eliminated during anxiolytic therapy without other systemic medications, which emphasizes the importance of eliminating the component of stress and anxiety in the treatment of such patients.