Anxiolytic Effect of Increased NREM Sleep after Acute Social Defeat Stress in Mice / 神经科学通报·英文版

Social defeat stress (SDS) plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression. Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS. However, the effect of acute SDS on sleep/wake behavior in mice varies between studies. In addition, whether sleep changes in response to stress contribute to anxiety is not well established. Here, we first investigated the effects of acute SDS on sleep/wake states in the active period in mice. Our results showed that total sleep time (time in rapid eye-movement [REM] and non-REM [NREM] sleep) increased in the active period after acute SDS. NREM sleep increased mainly during the first 3 h after SDS, while REM sleep increased at a later time. Then, we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS. Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state, while in mice with ad libitum sleep the anxiety rapidly faded away. Altogether, our findings suggest an anxiolytic effect of NREM sleep, and indicate a potential therapeutic strategy for anxiety.

Anxiolytic and free radical scavenging potential of Chinese celery (Apium graveolens) extract in mice

Objective To elucidate the anxiolytic and free radical scavenging effect of methanolic extract of Apium graveolens (A. graveolens) in adult C57BL/6 mice. Methods Sixty male mice were divided into 6 groups: control, vehicle, positive control and A. graveolens (125, 250 and 500 mg/kg). Different behavioral models of elevated plus maze, open field, light/dark, hole-board and pentobarbital-induced sleep were used to assess anxiety-like behavior. Biochemical parameters including monoamine oxidase-A (MAO-A) activity, lipid peroxidation, % inhibition of superoxide anion and glutathione peroxidase activity were measured. Histologic studies were also examined. Results Mice receiving various doses of A. graveolens (125, 250 and 500 mg/kg) showed an alleviation of anxiety-like behavior as evidenced by the battery of behavioral tests. Likewise, A. graveolens treatment was found to significantly decrease MAO-A activity, lipid peroxidation as well as cause a significant increase of % inhibition of superoxide anion and glutathione peroxidase activity in both cortex and striatum. The total number of survival neurons found in the frontal cortex and striatum was significantly higher than that of the vehicle-treated group. Conclusions Taken together, we showed that A. graveolens improve the behavioral changes which might be related to the inhibition of free radicals and modulation of MAO-A activity resulting in an increased number of survival neurons. Our findings suggest the therapeutic potential of A. graveolens in the treatment of anxiety.

Review on anxiolytic effect of natural small-molecule phenols / 中国中药杂志

Phenolic compounds have multiple bioactivities, such as anti-oxidant, anti-tumor, anti-bacterial, and anti-inflammatory activities. Recent literatures have demonstrated that flavonoids have a significant anti-anxiety effect on the central nervous system. In addition, studies showed that flavonoids acted as pro-drugs, which were transformed into smaller phenols through intestinal microflora. The small phenolic metabolites were crucial for the anxiolytic effects of these flavonoids, indicating that natural small-molecule phenols(NSMP) generally have anxiolytic activities. In this paper, the supporting evidences (before June 2016) from SciFinder database have been summarized. Furthermore, NSMPs were classified according to chemical structures; their anxiolytic effects, mechanisms, and the structure-activity relationships were also discussed.

Anxiolytic and free radical scavenging potential of Chinese celery (Apium graveolens) extract in mice

Objective: To elucidate the anxiolytic and free radical scavenging effect of methanolic extract of Apium graveolens (A. graveolens) in adult C57BL/6 mice. Methods: Sixty male mice were divided into 6 groups:control, vehicle, positive control and A. graveolens (125, 250 and 500 mg/kg). Different behavioral models of elevated plus maze, open field, light/dark, hole-board and pentobarbital-induced sleep were used to assess anxiety-like behavior. Biochemical parameters including monoamine oxidase-A (MAO-A) activity, lipid peroxidation,%inhibition of superoxide anion and glutathione peroxidase activity were measured. Histologic studies were also examined. Results: Mice receiving various doses of A. graveolens (125, 250 and 500 mg/kg) showed an alleviation of anxiety-like behavior as evidenced by the battery of behavioral tests. Likewise, A. graveolens treatment was found to significantly decrease MAO-A activity, lipid peroxidation as well as cause a significant increase of%inhibition of su-peroxide anion and glutathione peroxidase activity in both cortex and striatum. The total number of survival neurons found in the frontal cortex and striatum was significantly higher than that of the vehicle-treated group. Conclusions: Taken together, we showed that A. graveolens improve the behavioral changes which might be related to the inhibition of free radicals and modulation of MAO-A activity resulting in an increased number of survival neurons. Our findings suggest the therapeutic potential of A. graveolens in the treatment of anxiety.

Advanced in studies on anxiolytic effects of natural flavonoids / 中国中药杂志

Anxiety is one of the most common diseases endangering human health. Its pathogenesis is complex, the studies on the mechanisms of anxiety disorder are concentrated on neurotransmitter, neuroendocrine, immunologic system. Flavonoids are a kind of compounds which possess a variety of physiological activity, used in plenty of diseases. In recent years, researches of natural flavonoids on anti-anxiety were increasing, but contents were incomplete. It was just involved several neurotransmitters in research area. This paper is based on different anxiolytic effect mechanisms and structure-activity relationships of natural flavonoids, summarizing the researches of domestic and foreign, which can serve as a reference for further studies on anxiolytic effects of natural flavonoids.

PHYTOTHERAPY OF ANXIETY DISORDERS / Монголын эм зүй, эм судлал

The experiments on white Wistar rats have shown that Cimicifuga dahurica (TURCZ) Maxim. tincture and Schizonepeta multifi da (L.)Briq. extract have anxiolytic effect. Cimicifuga dahurica tincture stimulates exploratory activity of animals in the open fi eld test increasing the number of rearings and entries in the central area of the open fi eld and decreasing the number of boles and grooming acts. The Schizonepeta multifi da dry extract in the range of 50 to 300 mg/kg increases the number of water intake in the Vogel confl ict test. The effi cacy of the tested remedies – Cimicifuga dahurica tincture (at the doses of 0.5 and 1.0 ml/kg) and Schizonepeta multifi da extract (in the range of 100-300 mg/ kg) was higher on some parameters than that of valerian preparations. Key words: anxiolytic effect, Cimicifuga dahurica (TURCZ) Maxim. tincture, Schizonepetam multifi da (L.) Briq. extract. Introduction The development of medicinal remedies for the correction of functional impairments of the nervous system is important due to the prevalence of neuro-psychic diseases. At the same time, widely used anxiolytics negatively affect the human body causing hyper-sedation, myorelaxation, etc. [1, 3, 8]. Therefore, the plant remedies which have few side effects are prospective for pharmacological correction of the nervous system disturbances as alternative therapy or auxiliary remedy for increasing the effi cacy of receptor preparations [2, 5]. In this context the perennial plants Cimicifuga dahurica (TURCZ) Maxim. and Schizonepeta multifi da (L.) Briq. used in folk medicine as sedatives and for headaches are of great interest in the therapy of anxiety disorders [6, 7]. The aim of the study was to evaluate the infl uence of Cimicifuga dahurica tincture and Schizonepeta multifi da dry extract on the behavior of white rats in test systems characterizing anxiolytic effect of the medicinal remedy.

Anxiolytic effects of Dolichandrone falcata Seem., Bignoniaceae, stem-bark in elevated plus maze and marble burying test on mice / Efeitos ansiolíticos das cascas de Dolichandrone falcata Seem., Bignoniaceae, em teste do labirinto em cruz elevada e teste de esconder esferas, em camundongos

Dolichandrone falcata Seem., Bignoniaceae, is a deciduous tree commonly known as Medshingi in local areas of Toranmal region of Maharashtra, India. Its bark paste is applied on fractured or dislocated bones, used as a fish poison; bark juice is used in cases of menorragia and leucorrhoea. The leaves of the plant have afforded chrysin-7-rutinoside. The present study was carried out to investigate the anxiolytic effects of methanol extract (DFBM), ethyl acetate extract (DFBEA) and isolated compound DFB (V+VI) of D. falcata stem-bark using animal models. Anxiolytic effects were studied by elevated plus maze (EPM) and marble burying test (MBT) assay. The crude dried DFBM and DFBEA extract was prepared in doses of 100, 200 and 400 mg/kg whereas DFB (V+VI) compound was prepared in doses of 50, 100 and 200 mg/kg and were administered orally to mice for evaluation of anxiolytic activity. DFBEA 400 and DFB (V+VI) 200 mg/kg produced highly significant (p <0.01) anxiolytic effects in dose dependent manner by increasing the time spent on and the number of entries into the open arms of the EPM and by decreasing the number of marbles buried by mice in MBT test. This study showed that the DFBM, DFBEA extracts and DFB (V+VI) isolated compound possesses potential pharmacological active constituents flavonoids (like chrysin) which may be responsible for the anxiolytic activity.

Dolichandrone falcata Seem., Bignoniaceae, é uma árvore do tipo decidua, comumente conhecida como "Medshingi" na da região Toranmal de Maharashtra, na Índia. Uma pasta da casca é aplicada em fraturas ou luxação dos ossos e usada como veneno de peixe; o suco da casca é usada em casos de menorragia e leucorréia. Das folhas da planta foi isolado crisina-7-rutinoside. O presente estudo foi realizado para investigar os efeitos ansiolíticos do extrato metanólico (DFBM), acetato de etila (DFBEA) e compostos isolados DFB (V + VI) de D. falcata utilizando a casca do tronco em modelos animais. Os efeitos ansiolíticos foram estudados por labirinto em cruz elevada (EPM) e o ensaio de esconder esferas de mármore (MBT). Os extratos bruto e seco DFBM DFBEA foram preparados em doses de 100, 200 e 400 mg/kg, enquanto que o composto DFB (V + VI) foi preparado em doses de 50, 100 e 200 mg/kg e foram administrados em camundongos para avaliação da atividade ansiolítica. DFBEA 400 and DFB (V+VI) 200 mg/kg produziram efeitos ansiolíticos significantes (p<0.01), de maneira dose-dependente, por aumentar o tempo despendido e o número de entradas nos braços abertos do EPM e por diminuir o número de esferas escondidas pelos camundongos no teste do MBT. Este estudo mostrou que os extratos DFBM, DFBEA e o composto isolado DFB (V + VI), contendo flavonóides com potencial farmacológico (como a crisina) podem ser o responsável pela atividade ansiolítica.

Anxiolytic and sedative effects of a combined extract of Passiflora alata Dryander and Valeriana officinalis L. in rats / Efeito ansiolítico e sedativo do extrato combinado de Passiflora alata Dryander e Valeriana officinalis L. em ratos

Este trabalho investigou o efeito do extrato combinado de Passiflora alata Dryander e Valeriana officinalis L. (EPV) em ratos submetidos aos testes do labirinto em cruz elevado (LCE) e campo aberto (TCA). Nenhum efeito foi detectado após o tratamento agudo ou repetido por 3 ou 7 dias com EPV (5, 10 or 20 mg/kg, gavagem) no LCE e TCA. Entretanto, ratos tratados por 15 dias com EPV (20 mg/kg) mostraram aumento na porcentagem de entradas e tempo gasto nos braços abertos no LCE, sem alterar a atividade locomotora no TCA, comparado ao controle. Diazepan (droga de referência, i.p.), aumentou os mesmos parâmetros analisados no LCE e OFT após o tratamento agudo ou por 15 dias. O tratamento agudo com 300 ou 600 mg/kg do EPV diminuiu significativamente a atividade locomotora no TCA. Estes resultados mostram que EPV produz efeito ansiolítico e sedativo, com ampla margem de segurança para o efeito ansiolítico.

This work investigated the effects of a combined extract of Passiflora alata Dryander and Valeriana officinalis L. (EPV) in rats under going elevated plus maze (EPM) and open- test (OFT). No effects were detected after acute or repeated (3 or 7-days) treatment with EPV (5, 10 or 20 mg/kg, by gavage), on the EPM or the OFT. However, rats treated for 15 day (20 mg/kg) with EPV showed increased percentage of entries and time spent in the open arms on the EPM without alter locomotor activity in the OFT compared to control group. Acute or a 15 day administration of diazepam (2 mg/kg, i.p.), increased the same parameters on the EPM and OFT. Acute treatment with 300 or 600 mg/kg of EPV, decreased the locomotor activity in the OFT. Results suggest anxiolytic and sedative effects for the EPV and reveal a wide dose range for the anxiolytic effect.