The Study of TRPV1 Channels of the Central Nervous System and Their Effect on Anxiety in ICR Mice.

The TRPV1 channel is actively involved in various neuronal processes and is found in various structures of the nervous system, including peripheral and central neurons, sensory ganglia, spinal cord, and various parts of the brain. Due to its ability to respond to various stimuli, TRPV1 can have a significant impact on the body's responses to stress. Studies indicate the involvement of TRPV1 in the regulation of anxiety behavior. Suppression of TRPV1 activity leads to a decrease in the level of anxiety in animals, which indicates the importance of this channel in psychoemotional regulation. A promising compound for inhibiting this channel is the APHC3 peptide, which is a selective receptor antagonist. The results obtained this study show that this peptide has a pronounced anxiolytic effect, reducing the level of anxiety in the studied animals.

Daidzein ameliorates nonmotor symptoms of manganese-induced Parkinsonism in zebrafish model: Behavioural and biochemical approach.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a prevalent neurodegenerative movement disorder characterized by motor dysfunction. Environmental factors, especially manganese (Mn), contribute significantly to PD. Existing therapies are focused on motor coordination, whereas nonmotor features such as neuropsychiatric symptoms are often neglected. Daidzein (DZ), a phytoestrogen, has piqued interest due to its antioxidant, anti-inflammatory, and anxiolytic properties. Therefore, we anticipate that DZ might be an effective drug to alleviate the nonmotor symptoms of Mn-induced Parkinsonism. EXPERIMENTAL APPROACH: Naïve zebrafish were exposed to 2 mM of Mn for 21 days and intervened with DZ. Nonmotor symptoms such as anxiety, social behaviour, and olfactory function were assessed. Acetylcholinesterase (AChE) activity and antioxidant enzyme status were measured from brain tissue through biochemical assays. Dopamine levels and histology were performed to elucidate neuroprotective mechanism of DZ. KEY RESULTS: DZ exhibited anxiolytic effects in a novel environment and also improved intra and inter fish social behaviour. DZ improved the olfactory function and response to amino acid stimuli in Mn-induced Parkinsonism. DZ reduced brain oxidative stress and AChE activity and prevented neuronal damage. DZ increased DA level in the brain, collectively contributing to neuroprotection. CONCLUSION AND IMPLICATIONS: DZ demonstrated a promising effect on alleviating nonmotor symptoms such as anxiety and olfactory dysfunction, through the mitigation of cellular damage. These findings underscore the therapeutic potential of DZ in addressing nonmotor neurotoxicity induced by heavy metals, particularly in the context of Mn-induced Parkinsonism.

Midazolam for Anesthetic Premedication in Children: Considerations and Alternatives.

Premedication in anesthesia has long been used to reduce patient anxiety, increase patient compliance, and supplement the overall anesthetic. In pediatric populations, premedication also has the indirect benefits of reducing parental anxiety as well as both the incidence and severity of emergence delirium. Oral midazolam, selected for its ease of administration, short duration of action, and reliable anxiolytic and amnestic effects, has been a favorite choice in this role for decades. The side effect profile of midazolam is also relatively benign, heavily dose-dependent, and easily managed in the perioperative setting. While midazolam appears to be an ideal adjunct in the anesthetic care of pediatric patients, there is a growing body of evidence suggesting prolonged benzodiazepine exposure causes neurodevelopmental changes in infants. This evidence, along with the 2017 Food and Drug Administration (FDA) warning labels for the use of select anesthetic medications, including midazolam in children under the age of three, has led to some debate in the anesthetic community over the continued use of this anesthetic for premedication in pediatric populations. This article aims to educate the reader on the history of midazolam as a premedication agent in pediatric populations and examine the evidence supporting and against its continued use in this role.

Anxiolytic-like Effects by trans-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways.

Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light-dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent.

Pomegranate (Punica granatum L.) and its phytochemicals as anxiolytic; an underreported effect with therapeutic potential: A systematic review.

Anxiety is a mental disorder characterized by excessive concern about possible future threats that, if prolonged, becomes a pathology that must be controlled through psychotherapy and medication. Currently, the pharmacological treatment for anxiety involves the use of antidepressants and benzodiazepines; however, these treatments often come with adverse effects. Thus, there is a need to seek natural compounds that can help alleviate anxiety and reduce these side effects. On the other hand, pomegranate (PG) fruit is known to have important health benefits, which have been compiled in several reviews. However, its anxiolytic effect has not been thoroughly studied, and clinical research on this topic is lacking. The aim of this work was to conduct a systematic review of studies exploring the anxiolytic-like effect of PG and its phytochemicals. Databases such as Pubmed, ScienceDirect, Springer link, Google scholar, Worldwide science, and Web of science were searched for articles using predetermined terms. Inclusion criteria were established, and original articles that met these criteria were selected. The data collected included information on PG part and variety, species, sample size, anxiety model, dose, route and time of administration, reference drug, main results, and the mechanisms of action. Fifty-nine studies were found that reported the anxiolytic-like effect of PG and its phytochemicals such as anthocyanins, flavonoids, tannins, organic acids, and xanthonoids. The literature suggests that the mechanisms of action behind this effect involved the inhibition of the GABAergic receptor, NMDA, CaMKII/CREB pathway; the reduction of oxidative stress, inhibiting TLR4 and nNOS; modulation of cytokines and the expression of NFkB, GAD67, and iNOS, as well as the activation of Nrf2 and AMPK. PG and some of its phytochemicals could be considered as a novel alternative for the treatment of pathological anxiety. This review is the first to document the anxiolytic-like effect of PG.

Anxiolytic, Analgesic and Anti-Inflammatory Effects of Peptides Hmg 1b-2 and Hmg 1b-4 from the Sea Anemone Heteractis magnifica.

Acid-sensing ion channels (ASICs) have been known as sensors of a local pH change within both physiological and pathological conditions. ASIC-targeting peptide toxins could be potent molecular tools for ASIC-manipulating in vitro, and for pathology treatment in animal test studies. Two sea anemone toxins, native Hmg 1b-2 and recombinant Hmg 1b-4, both related to APETx-like peptides, inhibited the transient current component of human ASIC3-Δ20 expressed in Xenopus laevis oocytes, but only Hmg 1b-2 inhibited the rat ASIC3 transient current. The Hmg 1b-4 action on rASIC3 as a potentiator was confirmed once again. Both peptides are non-toxic molecules for rodents. In open field and elevated plus maze tests, Hmg 1b-2 had more of an excitatory effect and Hmg 1b-4 had more of an anxiolytic effect on mouse behavior. The analgesic activity of peptides was similar and comparable to diclofenac activity in an acid-induced muscle pain model. In models of acute local inflammation induced by λ-carrageenan or complete Freund's adjuvant, Hmg 1b-4 had more pronounced and statistically significant anti-inflammatory effects than Hmg 1b-2. It exceeded the effect of diclofenac and, at a dose of 0.1 mg/kg, reduced the volume of the paw almost to the initial volume. Our data highlight the importance of a comprehensive study of novel ASIC-targeting ligands, and in particular, peptide toxins, and present the slightly different biological activity of the two similar toxins.

Poststress social isolation exerts anxiolytic effects by activating the ventral dentate gyrus.

After aversive stress, people either choose to return to their previously familiar social environment or tend to adopt temporary social withdrawal to buffer negative emotions. However, which behavior intervention is more appropriate and when remain elusive. Here, we unexpectedly found that stressed mice experiencing social isolation exhibited less anxiety than those experiencing social contact. Within the first 24 h after returning to their previous social environment, mice experienced acute restraint stress (ARS) displayed low social interest but simultaneously received excessive social disturbance from their cage mates, indicating a critical time window for social isolation to balance the conflict. To screen brain regions that were differentially activated between the poststress social isolation and poststress social contact groups, we performed ΔFosB immunostaining and found that ΔFosB + signals were remarkably increased in the vDG of poststress social isolation group compared with poststress social contact group. There were no significant differences between the two groups in the other anxiety- and social-related brain regions, such as prelimbic cortex, infralimbic cortex, nucleus accumbens, etc. These data indicate that vDG is closely related to the differential phenotypes between the poststress social isolation and poststress social contact groups. Electrophysiological recording, further, revealed a higher activity of vDG in the poststress social isolation group than the poststress social contact group. Chemogenetically inhibiting vDG excitatory neurons within the first 24 h after ARS completely abolished the anxiolytic effects of poststress social isolation, while stimulating vDG excitatory neurons remarkably reduced anxiety-like behaviors in the poststress social contact group. Together, these data suggest that the activity of vDG excitatory neurons is essential and sufficient to govern the anxiolytic effect of poststress social isolation. To the best of our knowledge, this is the first report to uncover a beneficial role of temporal social isolation in acute stress-induced anxiety. In addition to the critical 24-h time window, activation of vDG is crucial for ameliorating anxiety through poststress social isolation.

[A role of neurosteroids in the pathogenesis of psychiatric disorders]. / Rol' neirosteroidov v patogeneze psikhicheskikh rasstroistv.

Despite the proven importance of neurosteroids in many physiological processes, their role in the pathogenesis of the most of psychiatric disorders remains relatively understudied. This article reviews the current clinical evidence on the effects of neurosteroids on the formation and treatment of anxiety disorder, depression, bipolar disorder, and schizophrenia. In particular, the article points out the ambivalent nature of the effects of neurosteroids on GABAA- and other receptors. We are especially interested in the anxiolytic and anxiogenic effects of some neurosteroids, the antidepressant effect of allopregnanolone in treating postpartum and other forms of depression, and the nature of short- and long-term mechanisms of antidepressant effects of neurosteroids of different types. The currently unproven hypothesis about the effect of changes in the level of neurosteroids on the course of bipolar disorder is also discussed, with an analysis of the scientific evidence on the development of schizophrenic symptomatology in relation to changing neurosteroid levels in the context of positive and cognitive symptoms.

GABAA and serotonergic receptors participation in anxiolytic effect of chalcones in adult zebrafish.

The prevalence of anxiety is a significant public health problem, being the 24th leading cause of disability in individuals affected by this disorder. In this context, chalcones, a flavonoid subclass obtained from natural or synthetic sources, interact with central nervous system (CNS) receptors at the same binding site as benzodiazepines, the primary drugs used in the treatment of anxiety. Thus, our study investigates the anxiolytic effect of synthetic chalcones derived from the natural product 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from Croton anisodontus Müll.Arg. in modulating anxiolytic activity via GABAergic and serotoninergic neurotransmission in an adult zebrafish model. Chalcones 1 and 2 were non-toxic to adult zebrafish and showed anxiolytic activity via GABAA receptors. Chalcone 2 also had its anxiolytic action reversed by the antagonist granisetron, indicating the participation of serotonergic receptors 5HTR3A/3B in the anxiolytic effect. In addition, molecular docking results showed that chalcones have a higher affinity for the GABAA receptor than DZP and binding in the same region of the DZP binding site, indicating a similar effect to the drug. Furthermore, the interaction of chalcones with GABAA and 5-HT3A receptors demonstrates the anxiolytic effect potential of these molecules.Communicated by Ramaswamy H. Sarma.

Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.

Anxiolytic effect of Korean Red Ginseng through upregulation of serotonin and GABA transmission and BDNF expression in immobilized mice.

Background: Anxiolytic properties of Korean Red Ginseng (KRG) have been previously reported. However, the exact mechanism(s) of action remains to be elucidated. The present study investigated the effect of KRG on immobilization-induced anxiety-like behaviors in mice and explored the involvement of the serotonin and GABA systems and BDNF in the anxiolytic action. Methods: Mice were orally administered with KRG (200 mg/kg/day) for 4 weeks and immobilized once daily for 2 h. p-Chlorophenylalanine (p-CPA) was intraperitoneally injected on day 22-28, and flumazenil or bicuculline was injected on day 25-28. After behavioral evaluations, brains were dissected for biochemical analyses. Results: KRG improved immobilization-induced anxiety-like behaviors in mice, as assessed by the elevated plus maze (EPM) and marble burying tests (MBT). The anxiolytic effect of KRG was comparable to that of fluoxetine, a reference drug clinically used for anxiety disorders. A serotonin synthesis inhibitor, p-CPA, blocked the effect of KRG in the EPM and MBT, indicating the requirement of serotonin synthesis for anxiolytic action. In addition, the anxiolytic effect of KRG was inhibited by bicuculline (a GABAA antagonist) in MBT, implying the involvement of GABA transmission. Western blotting analyses revealed that KRG upregulated the expression of tryptophan hydroxylase and GABAA receptor in the brain, which was blocked by p-CPA. Enhanced BDNF expression by KRG in the hippocampus was also indicated to mediate the anxiolytic action of KRG in immobilized mice. Conclusion: KRG exhibited the anxiolytic effect in immobilized mice by multiple mechanisms of action, involving enhanced serotonin and GABA transmissions and BDNF expression.

Anxiolytic Effect of Satureja montana Dry Extract and its Active Compounds Rosmarinic Acid and Carvacrol in Acute Stress Experimental Model.

BACKGROUND: Anxiety disorders are an important not only medical, but also social problem, affecting approx. 300 million people worldwide in 2019. Medications used in the treatment of anxiety are associated with many adverse reactions, which explains the increased use of herbal products as anxiolytics. METHODS: An anxiolytic activity of Satureja montana, rosmarinic acid and carvacrol after 14-day long administration on an animal model of acute stress was studied. For measurement of anxiolytic effect elevated plus maze, social interaction and Vogel tests were provided as well as examination of locomotor activity. RESULTS: The dry extract of Satureja montana at both tested doses significantly increased locomotor activity as well as the time spent in the social recognition, compared to the control groups. The extract reduced the time in the closed arms and the proportion of entries into open arms to total entries and increased the time in the open arms of elevated plus maze compared to the positive control group. Likewise, rosmarinic acid and carvacrol increased significantly the time spent with a new congener in the social interaction test. Both compounds reduced the ratio of entries into open arms to total entries similarly to the dry extract of Satureja montana. Only rosmarinic acid increased the time in the open arms and reduced the time in the closed arms. CONCLUSIONS: Satureja montana at both experimental doses exerted a significant anxiolytic activity in almost all the tests employed for evaluating anxious behavior. Carvacrol and rosmarinic acid showed a moderate anxiolytic effect.

Anxiolytic Effect of Peptides from Sea Anemone Heteractis crispa, Modulators of TRPV1 and ASIC Channels.

A number of studies confirmed the involvement of transient receptor potential vanilloid (TRPV) and acid-sensing (ASIC) ion channels in the physiological processes associated with the development of anxiety disorders. This makes their ligands new potential anxiolytic agents. We examined the efficacy of two peptides from the sea anemone Heteractis crispa, Hcr 1b-2 and HCRG21, affecting ASIC1a and TRPV1 channels, respectively, in the open field and elevated plus maze tests. According to the obtained data, HCRG21 significantly decreases both the level of anxiety and stimulates the activity of animals at doses of 0.01-1 mg/kg, whereas Hcr 1b-2 has a weak anxiolytic effect only at a dose of 0.1 mg/kg. The pharmacodynamic study showed that the HCRG21 has an anxiolytic effect for 2 h, and its effectiveness is higher than that of the reference drug.

GABAA receptor participation in anxiolytic and anticonvulsant effects of (E)-3-(furan-2-yl)-1-(2hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one in adult zebrafish.

Anxiety is a mental disorder that affects 25% of patients with epilepsy, and treatments for anxiety and seizures involve the use of benzodiazepines, a class of drugs that have many adverse effects such as decreased motor coordination, drowsiness, and sedation. Thus, new types of drugs with minimal side effects are of immediate requirement. Chalcones comprise a class of compounds with important therapeutic potential and have recently been investigated for their potential as anxiolytic and anticonvulsant agents. Therefore, this study aimed to evaluate the anxiolytic and anticonvulsant effects of the synthetic chalcone (E)-3-(furan-2-yl)-1-(2hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one (FURCHAL) using adult zebrafish as an animal model. Anxiolytic potential was assessed using the light/dark test and the anticonvulsant effect in 3-stage pentylenetetrazol (PTZ)-induced seizure tests. The mechanisms of the anxiolytic effect were analyzed using γ-aminobutyric acid (GABA) and the serotoninergic system. The anxiolytic effect of FURCHAL was verified by a reduction in fish locomotion, similar to diazepam (DZP), which may involve the GABAA receptor, as there was no reversal in the anxiolytic behavior of animals treated with FURCHAL by serotonergic antagonists. In addition, pretreatment with flumazenil blocked the anticonvulsant effect of FURCHAL and DZP at all three stages, indicating that FURCHAL also has anticonvulsant effects and that the presence of the α,ß unsaturated aromatic system and heterocyclic moiety in FURCHAL provided greater affinity for the GABAA receptors. Molecular docking revealed that the interactions involved in the formation of the protein-binding complex FURCHAL-GABAA are formed by three H-bonds involving the oxygen atoms of FURCHAL, and notably, complexes operated in the same region of the DZP site. Thus, this study adds new evidence and highlights that FURCHAL can potentially be used to develop compounds with anxiolytic and anticonvulsant properties.

Prophylactic Effect of Bovine Colostrum on Intestinal Microbiota and Behavior in Wild-Type and Zonulin Transgenic Mice.

The microbiota-gut-brain axis (MGBA) involves bidirectional communication between intestinal microbiota and the gastrointestinal (GI) tract, central nervous system (CNS), neuroendocrine/neuroimmune systems, hypothalamic-pituitary-adrenal (HPA) axis, and enteric nervous system (ENS). The intestinal microbiota can influence host physiology and pathology. Dysbiosis involves the loss of beneficial microbial input or signal, diversity, and expansion of pathobionts, which can lead to loss of barrier function and increased intestinal permeability (IP). Colostrum, the first milk from mammals after birth, is a natural source of nutrients and is rich in oligosaccharides, immunoglobulins, growth factors, and anti-microbial components. The aim of this study was to investigate if bovine colostrum (BC) administration might modulate intestinal microbiota and, in turn, behavior in two mouse models, wild-type (WT) and Zonulin transgenic (Ztm)-the latter of which is characterized by dysbiotic microbiota, increased intestinal permeability, and mild hyperactivity-and to compare with control mice. Bioinformatics analysis of the microbiome showed that consumption of BC was associated with increased taxonomy abundance (p = 0.001) and diversity (p = 0.004) of potentially beneficial species in WT mice and shifted dysbiotic microbial community towards eubiosis in Ztm mice (p = 0.001). BC induced an anxiolytic effect in WT female mice compared with WT female control mice (p = 0.0003), and it reduced anxiogenic behavior in Ztm female mice compared with WT female control mice (p = 0.001), as well as in Ztm male mice compared with WT BC male mice (p = 0.03). As evidenced in MGBA interactions, BC supplementation may well be applied for prophylactic approaches in the future. Further research is needed to explore human interdependencies between intestinal microbiota, including eubiosis and pathobionts, and neuroinflammation, and the potential value of BC for human use. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

Assessment of yogic relaxation techniques for its anxiolytic effects in patients requiring endodontic treatment: A prospective, randomized controlled study.

BACKGROUND: The aim of the study is to assess the anxiolytic effects of yogic relaxation technique (YRT) in patients requiring root canal treatment (RCT). MATERIALS AND METHODS: In this prospective, randomized, placebo-controlled study, 30 patients undergoing RCT with baseline visual analog scale for anxiety (VAS-A) of score >4 were divided into Group 1: YRTs; Group 2: alprazolam (0.25 mg/0.5 mg), and Group 3: placebo. After 30 min of completion of YRT, endodontic treatment was performed. Reduction in anxiety was analyzed using state anxiety score (domain) of the state-trait anxiety inventory scale. RESULTS: There was no significant difference in anxiety score 1 h before RCT between groups (P = 0.401). Ten minutes before (P < 0.0001) and after RCT (P < 0.0001), there was significant difference between groups (yogic relaxation vs. alprazolam [P < 0.0001]; yogic relaxation vs. placebo [P < 0.0001]). Ten minutes before RCT, yoga relaxation showed significant difference in anxiety score for pain versus alprazolam and placebo (P < 0.0001 for both). Ten minutes after RCT, the change from baseline in mean anxiety score for pain was significantly different with yogic relaxation (versus alprazolam [P = 0.043]; versus placebo [P = 0.002]). As per the global assessment of efficacy, the response was excellent in 9 (90%), 2 (20%), and 1 (10%) patients in yoga relaxation group, alprazolam group, and placebo group, respectively. Difference in response between three groups was significant (P < 0.0001). There was no significant difference in the global assessment of tolerability between three groups (P = 0.535). No adverse events were reported. CONCLUSION: Before RCT, YRT is an effective alternative to anxiolytic agents, alprazolam.

Anxiolytic-like effect of brominated compounds from the marine sponge Aplysina fulva on adult zebrafish (Danio rerio): Involvement of the GABAergic system.

Benzodiazepines are commonly used to treat disorders of the central nervous system, including anxiety. However, due to their adverse effects, there is a continuing interest in discovering new safe and effective drugs. Marine natural products have emerged as a prolific source of bioactive nitrogenated compounds. Aiming to discover new biologically active natural compounds, the marine sponge Aplysina fulva, a nitrogen-bearing heterocyst producer, was investigated. The main isolated compounds (4, 6, and 9) were evaluated on adult zebrafish (Danio rerio). A group of fishes (n = 6) was preliminarily subjected to acute toxicity, and open field tests using 0.1, 0.5, and 1.0 mg/mL (v. o.) of those compounds was performed. The anxiolytic effect was further investigated in the light/dark assay based on the locomotor response at zebrafish. Interactions through the GABAergic system were investigated using flumazenil, a silent modulator of GABA receptors. To improve the results, a study of molecular docking using the GABAA receptor also was performed. Based on the results, the bromotyrosine derivative compounds 4, 6, and 9 exhibited anxiolytic-like effects mediated by the GABAergic system.

A Review Focused on Molecular Mechanisms of Anxiolytic Effect of Valerina officinalis L. in Connection with Its Phytochemistry through in vitro/in vivo Studies.

Valeriana officinalis L. (Valerianaceae) is one of the most reputed ancient medicinal plants used in modern phytotherapy and traditional medicine. Its root extract is one of the most effective herbal sedatives and tranquilizers, where the plant is also used for the treatment of gastrointestinal spasms. V. officinalis has complex phytochemistry consisting of the esterified iridoid derivatives known as valepotriates (e.g., valtrate, didrovaltrate, isovalerenic acid), sesquiterpenes (e.g., valerenic acid), flavonoids (e.g., linarin, apigenin), lignans (e.g., pinoresinol, hydroxypinoresinol), alkaloids (e.g., actinidine, valerine), triterpenes (e.g., ursolic acid), monoterpenes (e.g., borneol, bornyl acetate). Among them, valerenic acid is a marker compound for standardization of the root extracts of the plant and has been reported in many in vitro/in vivo studies to be responsible for anxiolytic action of the plant. Although modulation of gamma-aminobutyric acid (GABA) receptors has been revealed to be the leading mechanism of the plant-based on the existence of valerenic acid, several studies described the interaction of valerenic acid with glutamergic receptors. In addition to valerenic acid, isovaleric acid, didrovaltrate, borneol, and some lignans have also been proposed to contribute to the anxiolytic effect of the plant. In the current review, the data selectively scrutinized from the in vitro/in vivo studies about identifying anxiolytic molecular mechanisms of V. officinalis is focused.

Anxiolytic effect of an extract of Salvia miltiorrhiza Bunge (Danshen) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has demonstrated in modern studies for its pharmacological activities in treatments of CNS disorders like insomnia, dysphoria. However, its application on anxiolytic effect from the ethanol extract of Salvia miltiorrhiza Bunge (SMEtOH) has not yet been reported. MATERIALS AND METHODS: This study investigated the anxiolytic effect of the SMEtOH using the elevated plus-maze test (EPM) and the hole-board test (HBT) with diazepam and buspirone as positive controls. Also, the spontaneous locomotor activity of mice had been investigated in the open field. Further, we have illustrated the anxiolytic mechanisms of SMEtOH with its influencing upon GABAergic and/or serotonergic nervous systems via a method that SMEtOH was co-administered with flumazenil, a benzodiazepine (BZD) antagonist, or a drug (WAY-100635), a selective 5HT1A receptor antagonist. RESULTS: In hole-board test, results presented that SMEtOH increased head-dip counts and duration time. On the other hand, a decrease in spontaneous locomotor activity was observed. In the EPM test, SMEtOH increased the percentage of open-arm entries and the percentage of time spent in open arms. However, when SMEtOH co-administered with flumazenil or WAY-100635, the anxiolytic effect of SMEtOH was significantly counteracted. CONCLUSION: From these results, we can conclude that the anxiolytic mechanism of SMEtOH is exerted through an activation of the BZD and 5HT1A receptors.

Neuroprotective Potency of Saffron Against Neuropsychiatric Diseases, Neurodegenerative Diseases, and Other Brain Disorders: From Bench to Bedside.

The increasing morbidity rates of brain disorders and conditions such as anxiety, depression, Alzheimer's disease, and Parkinson's disease have become a severe problem in recent years. Although researchers have spent considerable time studying these diseases and reported many positive outcomes, there still are limited drugs available for their treatment. As a common traditional Chinese medicine (TCM), saffron was employed to treat depression and some other inflammatory diseases in ancient China due to its antioxidant, anti-inflammatory, and antidepressant properties. In modern times, saffron and its constituents have been utilized, alone and in TCM formulas, to treat neuropsychiatric and neurodegenerative diseases. In this review, we mainly focus on recent clinical and preclinical trials of brain disorders in which saffron was applied, and summarize the neuroprotective properties of saffron and its constituents from chemical, pharmacokinetic, and pharmacological perspectives. We discuss the properties of saffron and its constituents, as well as their applications for treating brain disorders; we hope that this review will serve as a comprehensive reference for studies aimed at developing therapeutic drugs based on saffron.