Anxiolytic Effects Research Articles

Evaluation of ethanolic extract of Piper methysticum leaves on anxiolytic activity of mice

The ethanol extract of Piper methysticum, commonly known as kava, has shown promising results in reducing anxiety. Studies suggest it may have anxiolytic effects, potentially offering a natural alternative to conventional anxiety treatments. The ethanolic extract of Piper methysticum can increase the duration of action. It can also increase the time spent in open arm, entry in open arm (in elevated plus model) as well as increase the time spent in light field (in Light Dark field) thus we can conclude that it can also possesses Anxiolytic action. The ethanolic extract of Piper methysticum possesses an anxiolytic like activity without sedative side effect. The corticosterone level in mice is increased when they got anxiety. So when the plasma corticosterone level of mice is checked in control group its turn out to be 10.28±0.52. It gets decreased with increase in doses. When treated with low dose of Aqueous extract is 7.28±1.44 is less effective than low dose of Ethanolic extract that is 6.22±1.28. Same as that high dose of extract shows the corticosterone level was 6.24±2.28 which was also less effective than high dose of ethanolic extract which was 5.52±0.32. Most effectively stress was decreased when treated with the Standard drug (Alprazolam) which shows plasma corticosterone level was 1.24±0.36. The mice of Piper methysticum extract (300 &600 mg/kg/ p.o.) treated group showed significantly (p<0.05) increased in body water intake as compared to the control group. Results showed that synthesized extract is very effective for the treatment of anxiety. Keywords: Piper methysticum; anxiolytic activity; Anthraquinones; Light Dark model

Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states.

Psychedelics hold promise as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated the specific neurons modulated by a psychedelic to determine their role in driving behavior. Using a light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive neurons in the medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that the psychedelic drove network-level activation of multiple cell types beyond just those expressing 5-hydroxytryptamine 2A receptors. We labeled psychedelic-responsive mPFC neurons with an excitatory channelrhodopsin to enable their targeted manipulation. We found that reactivation of these cells recapitulated the anxiolytic effects of the psychedelic without driving its hallucinogenic-like effects. These findings reveal essential insight into the cell-type-specific mechanisms underlying psychedelic-induced behavioral states.

Reversal Potentials of Tween 20 in ABC Transporter-Mediated Multidrug-Resistant Cancer and Treatment-Resistant Depression Through Interacting with Both Drug-Binding and ATP-Binding Areas on MDR proteins

Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters in vitro and to evaluate its potential for overcoming drug resistance in two models: an in vitro cancer MDR model and an in vivo TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the in vivo depression-like behavior model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both in vitro and in vivo, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.

Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats

AimsWe aimed to investigate the anxiolytic effect of darbepoetin alpha (DEPO), an erythropoietin derivative, in a neuroinflammation model regarding different behaviors and biological pathways.MethodsForty adult male Wistar albino rats were divided into four groups (control, LPS, DEPO, and DEPO + LPS). The rats were treated with 5 µg /kg DEPO once a week for four weeks, after which neuroinflammation was induced with 2 mg/kg lipopolysaccharide (LPS). The elevated plus maze, open-field, and light‒dark box tests were conducted to assess anxiety levels. Harderian gland secretions were scored via observation. Tumor necrosis factor alpha (TNF-α), Interleukin-1-beta (IL-1β), brain-derived growth factor (BDNF), serotonin, cortisol, total antioxidant/oxidant (TAS/TOS), and total/free thiol levels were measured in the prefrontal cortex, striatum, and serum.ResultsDEPO had a potent anxiolytic effect on both DEPO and DEPO + LPS groups. Compared to the control group, DEPO administration caused an increase in serotonin and BDNF levels and decreased basal cortisol and TNF-α levels in naive rats. IL-1β did not alter after DEPO administration in naive rats. Prophylactic DEPO treatment remarkably downregulated cortisol, IL-1β, and TNF-α in the DEPO + LPS group. In addition, prophylactic DEPO administration significantly attenuated the decrease in serotonin and BDNF levels in the DEPO + LPS group. Furthermore, DEPO ameliorated excessive harderian gland secretion in the DEPO + LPS group. Compared with those in the control group, the free thiol content in the serum increased after DEPO administration. No similar effect was seen in the DEPO + LPS group receiving prophylactic DEPO. TAS showed no difference among all experimental groups. DEPO administration increased TOS and OSI in the serum and prefrontal cortex but not in the striatum. This effect was not seen in the DEPO + LPS group.ConclusionDarbepoetin alpha had an anxiolytic effect on many physiological mechanisms in a neuroinflammation model and naive rats.

Metabolomic Analysis Reveals the Linkage between Sleep-Enhancing Effects and Metabolite Biomarkers and Pathways of Different Casein Hydrolysates in Chronic Unpredictable Mild Stressed Mice.

Casein hydrolysates have been proven to exert varying sleep-enhancing and anxiolytic effects due to their distinct release of potential peptides. However, their underlying sleep-enhancing mechanisms at the metabolic level remain unclear. This study aims to investigate the potential sleep-enhancing mechanism of casein hydrolysates through an integrated approach of untargeted and targeted metabolomics in CUMS-induced anxiety mice for the first time. The results showed seven potential biomarkers were identified and screened using orthogonal partial least-squares discriminant analysis, random forest model, and pathway analysis, including ornithine, l-proline, l-prolinamide, inhibitory neurotransmitters gamma-aminobutyric acid, 5-HIAA, fumaric acid, and 4-oxoglutaramate. Moreover, casein hydrolysates exerted sleep-enhancing effects through multiple metabolic pathways, mainly including the GABAergic system, tryptophan metabolism, and cAMP response signaling pathway, which was validated by targeted metabolomics and vital protein expressions. It was interesting that casein hydrolysates with diverse representative peptide compositions exhibited varying activity, which could be attributed to distinct alterations in metabolites via different pathways.

Xylopia parviflora (A. rich.) benth. Mitigates anxiety behavior and chronic mild stress-induced depression-like behavior in mice: The involvement of biogenic amine neurotransmitters, cyclooxygenase-2 and stress biomarkers in its antidepressant activity

BackgroundXylopia parviflora is a novel botanical in Modern Chinese Medicine that contains bioactive constituents including alkaloids, flavonoids, and terpenoids, which are the pharmacologically active components in various Chinese herbal formulations such as Coptis chinensis (alkaloid-rich herbs), Ginkgo biloba (flavonoid-rich herbs) and Artemisia annua (terpenoid-rich herbs). ObjectiveThis investigation sought to evaluate the anxiolytic and antidepressant-like effects of the hydroethanol leaf extract of Xylopia parviflora using mouse models. We elucidated the roles of noradrenaline, serotonin, cyclooxygenase-2, and reactive oxidative species in mediating its antidepressant effects, providing a fresh perspective on the pharmacological activity of Xylopia parviflora. MethodsThe acute toxicity of XPE was assessed following OECD guideline 420. Established behavioral tests were used to evaluate the anxiolytic (including the hole-board, open field, elevated plus maze, and light/dark exploration assessments) and antidepressant (encompassing the forced swim and tail suspension tests) effects of the extract. Mice received treatments of distilled water (10 mL/kg, serving as the negative control), fluoxetine (20 mg/kg, acting as the reference medication), and XPE (at doses of 50, 100, and 200 mg/kg). The concentrations of noradrenaline, serotonin, and COX-2 within the brain tissue were quantified using ELISA kits. The levels of antioxidant biomarkers were evaluated using standardized commercial assay kits. ResultsThe oral/intraperitoneal LD50 for the extract was established at 2000 mg/kg. In the behavioral assessments designed to measure anxiolytic effects, XPE significantly mitigated anxiety levels in mice, as evidenced by an increase in exploratory behaviors (including head dips, sectional crossings, general square crossings, rearing, and assisted rearing) and an increased time spent in the brightly illuminated compartments. Concerning the antidepressant evaluations, XPE significantly reduced depression-like behaviors in mice, which was indicated by an increased latency to immobility and a decrease in the duration of immobility. XPE was found to modulate noradrenaline and serotonin transmissions, attenuate oxidative species, and inhibit COX-2 activity. ConclusionThe findings above demonstrate that Xylopia parviflora possesses anxiolytic and antidepressant-like activities. The antidepressant property of XPE, as revealed in this study, may be attributable to the enhancement of biogenic amines (specifically noradrenaline and serotonin), the suppression of oxidative species, and the inhibition of COX-2 activity.

Impact d’HypnoVR©, associé à une anesthésie locale, sur la douleur et l’anxiété ressenties lors d’une ponction ovocytaire

Objective : Virtual reality with Snow World shows a 45% decrease in painful peaks during the care of burn victims. Hypnosis has anxiolytic effect and modulate the response to pain. HypnoVR© is based on many concepts recognized in medicine accessible without specific training. In our practice, 95% of oocyte pick-up are made with local anesthesia and simple premedication, whereas conscious sedation is recommanded in Europe. HypnoVR© is systematically offered during oocyte pick-up. Our study had to compare the pain felt between the 2 group with or without HypnoVR©, also anxiety, tolerance and satisfaction of patients.Method : It was a prospective comparative, non-randomized, single-center, open-label study. We included all patients who were to benefit from an oocyte pick-up from 18 to 43 years-old. The usual protocol of pick-up was used and it was possible to add HypnoVR©. A questionnaire was distributed to each patient to collect their opinion.Results : A total of 112 patients were included, 60 without HypnoVR© and 52 with HypnoVR© ; 2 were excluded from the main analysis for missing data. There is no statistically significant difference in pain and anxiety between the groups. Patients are satisfied : 90.20% (n=46/52) would like to use it again and 98.04% (n=50/52) would recommend it.Conclusion : Despite the absence of a statistically significant difference, patients are satisfied with HypnoVR© and tolerance is good. It seems interesting to be able to offer it during oocyte pick-up.

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

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

L’intoxication au protoxyde d’azote : un nouveau défi pour la biologie médicale

AbstractNitrous oxide (N2O) is a gas used in medicine for its anesthetic and analgesic properties, and in industry as an oxidizing gas or propellant. This gas is also available on self-service for food use. In recent years, its use has been increasingly diverted to recreational purposes. Between 2020 and 2021, the number of serious cases of intoxication increased by 320% in France, demonstrating a major public health concern. It is also a problem for road safety, with an increase in the number of road accidents linked to the consumption of this gas. Nitrous oxide causes both short-term effects (euphoria, disorientation, etc.) and long-term effects (sensory and motor neurological disorders and thrombosis). This gas acts on the central nervous system, inducing anxiolytic, anesthetic, antidepressant and analgesic effects. Nitrous oxide is difficult to quantify because of its rapid elimination. Biological investigation is thus based on secondary anomalies linked to vitamin B12 inactivation: increased methylmalonic acid and homocysteine levels. However, these two biological markers are not specific to nitrous oxide intoxication. To improve patient support, we need to find new biological markers that are more specific to nitrous oxide intoxication.

Unilateral and bilateral theta burst stimulation for treatment-resistant depression: Follow up on a naturalistic observation study

ObjectivesTheta burst stimulation (TBS) is a novel and faster modality of transcranial magnetic stimulation, which is showing promise as a treatment-resistant depression (TRD) treatment. Though TBS can be applied unilaterally or bilaterally, few studies have compared the effectiveness of both approaches in a naturalistic clinical sample. In this retrospective chart review, we aimed to: (1) replicate previous bilateral sequential TBS effectiveness in a larger cohort of patients at a single centre, (2) present treatment outcome data between unilateral and bilateral TBS approaches, (3) investigate baseline factors associated with our observed outcomes, and (4) examine the sustainability of response, with follow-up data up to 6 months from patients. MethodsWe included 161 patients who received TBS (unilateral: n = 64 (40%), 45.55 ± 14.25 years old, 55% females; bilateral: n = 97 (60%), 47.67 ± 15.11 years old, 58% females). ResultsFirstly, we observed 47% response and 34% remission in the bilateral group, replicating findings from a smaller naturalistic study from our group; patients receiving unilateral TBS displayed 36% response and 26% remission, with no significant differences found between unilateral and bilateral TBS in remission and response rates. Secondly, bilaterally stimulated patients needed fewer treatments than those stimulated unilaterally (27 vs 29 on average respectively, t [159] = 3.31, p = .001), and had significantly lower anxiety symptoms post treatment (GAD-7) relative to patients receiving unilateral stimulation, F (1,148) = 3.95, p = .049. Thirdly, no baseline factors were found to predict treatment outcomes. Lastly, after six months, 69% of patients who met the response criteria did not require additional treatment or a change in medication. ConclusionsOur findings support the efficacy and tolerability of TBS in TRD and indicate that bilateral TBS may have a superior anxiolytic effect and offer a slightly faster time to response.

Trans-Ferulic acid reduces the sedative activity of diazepam in thiopental sodium-induced sleeping mice: A potential GABAergic transmission.

trans-Ferulic acid (TFA), a bioactive compound found in many plants, has been recognized for its diverse pharmacological activities, including potential neurological benefits. Previous studies suggest that TFA exerts anxiolytic effects via GABAergic pathways. This study aimed to investigate the sedative effects of TFA and its possible molecular mechanisms through in vivo and in silico approaches. Adult Swiss mice were randomly divided into six groups (n=7): control (vehicle), standard (DZP: Diazepam at 3mg/kg, p.o.), three test groups (TFA at 25, 50, and 75mg/kg, p.o.), and a combination group (TFA: 50mg/kg with DZP: 3mg/kg, p.o.). Thirty minutes post-treatment, thiopental sodium (TS) at 40mg/kg was administered to induce sedation, and latency as well as duration of sleep, were observed for up to 4h. In silico studies were conducted with GABAA receptor subunits (α1 and β2) to elucidate the possible molecular interactions. The results demonstrated that TFA significantly reduced latency and extended sleep duration in a dose-dependent manner compared to the control. Additionally, TFA combined with DZP further significantly (p<0.001) enhanced these effects. In silico analysis revealed that TFA and DZP exhibited strong binding affinities with the GABAA receptor subunits (α1 and β2) in the identical binding sites, with binding energies of -6.8 and-8.7kcal/mol, respectively. Collectively, TFA exerted a mild sedative effect in TS-induced sleeping mice and modulated the activity of DZP, likely through interactions with GABAA receptors. TFA showed promising activity as a potential candidate for managing sleep disorders such as insomnia.

Dopamine D4 receptors in the lateral habenula regulate anxiety-related behaviors in a rat model of Parkinson's disease

Although the output of the lateral habenula (LHb) controls the activity of midbrain dopamine (DA) and 5-hydroxytryptamine (5-HT) containing systems, which are implicated in the pathophysiology of anxiety, it is not clear how activation and blockade of LHb D4 receptors affects anxiety-like behaviors, particularly in Parkinson’s disease related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) in rats induced anxiety-like behaviors, which attribute to hyperactivity of LHb neurons and decrease in the level of DA in the medial prefrontal cortex (mPFC), amygdala and ventral hippocampus (vHip) compared to sham-operated rats. Intra-LHb injection of D4 receptor agonist A412997 induced or increased the expression of anxiety-like behaviors, while injection of D4 receptor antagonist L741742 showed anxiolytic effects in sham-operated and the SNc-lesioned rats. However, the doses producing behavioral effects in the lesioned rats were higher than those of sham-operated rats. Intra-LHb injection of A412997 increased firing rate of LHb neurons, and decreased levels of DA and 5-HT in the mPFC, amygdala and vHip; conversely, L741742 decreased firing rate of LHb neurons, and increased levels of DA and 5-HT in two groups of rats. Compared to sham-operated rats, the duration of A412997 and L741742 action on the firing rate of neurons was markedly shortened in the lesioned rats. Collectively, these findings suggest that D4 receptors in the LHb are involved in the regulation of anxiety-like behaviors, and degeneration of the nigrostriatal pathway down-regulates function and/or expression of these receptors.

The Effect of Music Distraction on Dental Anxiety During Invasive Dental Procedures in Children and Adults: A Meta-Analysis.

Background: Dental anxiety and odontophobia are common issues, leading to challenges with oral hygiene and dental health. Music distraction offers an effective and side effect-free solution to alleviate pain and increase the acceptability of dental treatments. Our meta-analysis aimed to assess the efficacy of music distraction in reducing patient anxiety during invasive dental procedures in children and adults. Methods: The PubMed, Web of Science, and Embase databases were searched for clinically controlled trials, using the keywords "music" and "dental anxiety". The main outcome measured was the anxiety score. A meta-analysis was conducted using a random-effects model to estimate the standardized mean differences (SMDs). The subgroup analyses were conducted based on age groups, music preferences, and music styles. The research protocol has been registered with PROSPERO (Registration ID: CRD42022357961). Results: A total of 24 controlled clinical trials involving 1830 participants met the inclusion criteria for the meta-analysis. Music distraction significantly reduced dental anxiety during invasive procedures under local anesthesia (SMD, -0.50; 95% CI, -0.80 to -0.21; p = 0.0009; I2 = 83%). Our subgroup analysis revealed that music distraction was more effective in adults (SMD, -0.51; p = 0.0007) than in children (SMD, -0.47; p = 0.13) in reducing dental anxiety. Regarding music selection, music chosen by the participant (SMD, -1.01; p = 0.008) demonstrated more anxiolytic effects than by the author (SMD, -0.24; p = 0.02). Regarding music styles, classical music (SMD, -0.69; p = 0.009) was associated with better anxiolytic effects in adults. Conclusions: Our meta-analysis supports the use of music to alleviate dental anxiety during invasive procedures. Listening to classical or customized music can serve as an effective adjunct to outpatient surgical care in dental clinics.

O IMPACTO DA REGULAÇÃO DO SISTEMA ENDOCANABINOIDE NA FARMACOTERAPIA DA ANSIEDADE E DO ESTRESSE

This article addresses the impact of regulation of the endocannabinoid system on the pharmacotherapy of anxiety and stress, topics of increasing relevance in neuroscience and pharmacology. The endocannabinoid system, composed of receptors, endocannabinoids and enzymes responsible for their synthesis and degradation, plays a fundamental role in modulating several physiological functions, including the regulation of stress and anxiety. Cannabidiol (CBD), a phytocannabinoid, has stood out for its anxiolytic and modulating effects on the endocannabinoid system, presenting itself as a promising therapeutic alternative for anxiety disorders. The objective of the study was to analyze the therapeutic effects of regulating the endocannabinoid system in the treatment of anxiety and stress, focusing on the benefits and limitations of using CBD. To this end, a bibliographic review of studies published between 2010 and 2024 was carried out, using databases such as PubMed, SciELO and Google Scholar. Inclusion criteria involved peer-reviewed studies that addressed the relationship between the endocannabinoid system and anxiety disorders. The results showed that CBD can significantly reduce symptoms of anxiety and stress, with few side effects. However, there are still gaps regarding optimal dosage and drug interactions, which limits its widespread clinical adoption. Regulation of the medicinal use of cannabis has also proven to be an obstacle in several countries. It is concluded that, despite the challenges, the use of cannabinoids such as CBD represents a promising approach, requiring greater investment in clinical research and adequate regulation.

Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways.

Anxiety is a natural response to stress, characterized by feelings of worry, fear, or unease. The current research was conducted to investigate the anxiolytic effect of indirubin (IND) in different behavioral paradigms in Swiss albino mice. To observe the animal's behavioural response to assess anxiolytic activity, different tests were performed, such as the open-field (square cross, grooming, and rearing), swing, dark-light, and hole cross tests. The experimental mice were administered IND (5 and 10 mg/kg, p.o.), where diazepam (DZP) and vehicle were used as positive and negative controls, respectively. In addition, a combination treatment (DZP+IND-10) was provided to the animals to determine the modulatory effect of IND on DZP. Molecular docking approach was also conducted to determine the binding energy of IND with the GABAA receptor (α2 and α3 subunits) and pharmacokinetics were also estimated. The findings revealed that IND dose-dependently significantly (p<0.05) reduced the animal's movement exerting calming behavior like DZP. IND also demonstrated the highest docking score (-7.7 kcal/mol) against the α3 subunit, while DZP showed a lower docking value (-6.4 kcal/mol) than IND. The ADMET analysis revealed that IND has proper drug-likeness and pharmacokinetic characteristics. In conclusion, IND exerted anxiolytic effects through GABAergic Pathways.

Silexan in anxiety, depression, and related disorders: pharmacological background and clinical data.

We present a narrative review of clinical trials investigating the anxiolytic and antidepressant effects of silexan, an active substance derived from lavender oil and summarize nonclinical findings from pharmacological studies supporting its therapeutic use. Six studies investigated the efficacy of the lavender oil in patients with subthreshold and generalized anxiety disorders as well as in mixed anxiety and depressive disorder (MADD). Furthermore, we present data indicating that silexan may influence sleep quality as well as anxiety or depressive disorders in individuals with post-COVID-19. Silexan taken orally at a daily dose of 80mg for 10 weeks was significantly superior to placebo in reducing psychic and somatic symptoms of anxiety and was as effective as 0.5mg/d lorazepam and 20mg/d paroxetine. In patients with mild or moderate major depression, silexan was superior to placebo and comparably effective to 50mg/d sertraline. Significant antidepressant effects were also observed in MADD and depression co-morbid with anxiety. The herbal product had a beneficial effect on activities of daily living and health-related quality of life. Adverse events associated with silexan in clinical trials were limited to eructation and mild, transient gastrointestinal complaints. The herbal product was not associated with drug interactions, sedation, sleep disturbance, dependence and abuse potential, sexual dysfunction, weight gain or withdrawal symptoms. Silexan was therefore safe and effective in subthreshold and syndromal anxiety disorders and in major depression.

Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors

Background/Objectives: In post-traumatic stress disorder (PTSD), anxiety-like symptoms are often associated with elevated noradrenaline levels and decreased serotonin. Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat anxiety, but elevated serotonin has been observed in some anxiety disorders. This study investigates stress-induced anxiety as an immediate effect of chronic stress exposure using the predator stress paradigm. Methods: We examined serotonin levels, serotonin transporter (SERT), and 5-HT3A receptor gene expression in response to stress. The effects of SSRIs (paroxetine, sertraline) and resveratrol on these parameters were also analyzed, alongside co-treatment with resveratrol and sertraline. Results: Chronic stress exposure led to a significant increase in serotonin levels and upregulation of SERT and 5-HT3A receptor expression. SSRIs failed to prevent anxiety or reduce serotonin levels, partly due to suppressed SERT expression. Resveratrol downregulated SERT and 5-HT3A expression less than SSRIs but effectively reduced anxiety and restored serotonin, likely by upregulating MAO-A expression. Co-treatment with resveratrol and sertraline produced the strongest anxiolytic effect. Conclusions: Elevated serotonin and increased expression of SERT and 5-HT3A receptor genes are key factors in stress-related anxiety. Resveratrol and SSRIs target these mechanisms, suggesting potential therapeutic strategies for anxiety disorders. Future research will focus on further elucidating the serotonergic mechanisms involved and identifying new anxiolytic drug targets.

General anesthesia activates a central anxiolytic center in the BNST

Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects, but the underlying mechanisms remain unclear. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that are activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNSTGA). The majority of ovBNSTGA neurons express neurotensin receptor 1 (Ntsr1) and form circuits with brain regions known to regulate anxiety and stress responses. Optogenetic activation of ovBNSTGA or ovBNSTNtsr1 neurons significantly attenuated anxiety-like behaviors in both naive animals and mice with inflammatory pain, while inhibition of these cells elevated anxiety. Activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety by modulating autonomic responses. Our study identifies ovBNSTGA/ovBNSTNtsr1 neurons as a common neural substrate mediating the anxiolytic effect of low-dose anesthetics and a potential therapeutic target for treating anxiety-related disorders.

Perceived Changes in Anxiety Symptom Burden During Treatment with Bryophyllum pinnatum: A Prospective, Single-Arm Study

Background/Objectives: Bryophyllum spp. preparations are widely used in Anthroposophic Medicine, most often for mental and behavioral disorders, including anxiety. Studies in animals revealed various anxiolytic and neurosedative effects for Bryophyllum pinnatum. We set out to investigate the effectiveness of Bryophyllum 50% chewable tablets, a product registered without indication by means of notification in Switzerland, in the treatment of anxiety symptoms in psychiatric and psychosomatic patients. Methods: A total of 99 patients with anxiety symptoms were recruited from the waiting list for an inpatient stay at the hospital “Klinik Arlesheim”, Department of Psychiatry and Psychosomatics; of these, 54 completed the study and returned fully completed questionnaires. Patients were treated with Bryophyllum 50% chewable tablets (350 mg tablets, made from leaf press juice, 3 × 2 per day; Weleda AG Arlesheim, Switzerland) and filled out questionnaires at baseline and after two and three weeks of tablet intake. The primary endpoint of the study was the change in anxiety symptoms measured with the Beck Anxiety Inventory (BAI). Results: A clinically relevant decrease in BAI score from baseline (27.4 ± 12.0) to after two (22.4 ± 12.1; p &lt; 0.001) and three (20.6 ± 12.9; p &lt; 0.001) weeks of treatment was observed. Additional improvements were observed in the secondary endpoints (including in depression, sleep quality, and stress); tolerability and compliance were very good. Conclusions: The results suggest that Bryophyllum 50% chewable tablets have beneficial effects on anxiety-related symptoms. Since the study design does not allow us to conclude causality between treatment and observed improvements, a randomized clinical trial is urgently needed.

An optimized whole-body corticosteroid hormones quantification method by LC-MS/MS for assessing stress levels in European glass eels (Anguilla anguilla)

The European eel (Anguilla anguilla) juvenile stage exhibits facultative estuarine migration. The causes of this behavior are yet unknown but it may have an impact on the population's fate by altering the sex ratio of the population. Recent studies have highlighted potential stress-related issues in glass eels settling in estuaries but studying stress response in small organisms requires sensitive, accurate and precise analytical methods. The aims of the present study are (i) to develop a whole-body Liquid Chromatography-Mass Spectrometry (LC-MS/MS) method for the simultaneous determination of several stress hormones in low-body mass fish; (ii) to apply this method to glass eels to study their responses to acute stress (iii) to test the effect of anxiolytics (diazepam) on these responses. Our results showed that enhanced LC-MS/MS analysis reduced detection limits and improved accuracy and precision for the quantification at the individual level. Following an acute stress, cortisol concentration significantly increased in glass eels and a 15 h diazepam exposure significantly reduced cortisol levels highlighting a marked anxiolytic effect on this species.