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Ethnopharmacological Relevance: Galphimia glauca is a Mexican medicinal plant used to treat anxiety, fear, phobia and stress as it possesses sedative properties which produce a calming effect. Although some chemical and pharmacological studies have already been carried out on G. glauca, there are still new chemical entities from this plant whose anxiolytic activity should be established., Aim of the Study: To validate the use of G. glauca growing in Cuernavaca, Morelos, as an anti-stress agent, through the purification and structural identification of its extracts' chemical constituents; the analysis of the biogenetic relationship of its chemical compounds, and its biological evaluation to demonstrate its traditional use as anxiolytic agents., Materials and Methods: The structures of all isolated compounds were established based on their spectroscopic and spectrometric data. The structure of compound 2 was corroborated through X-Ray. The anxiolytic and sedative-like activities were assessed by the open-field, hole-board and exploration cylinder test., Results: The nor-triterpenes glaucacetalin E (1) and galphimidin B (2) were isolated for the first time along with seven other known compounds, one of them galphimidin (3), from the CHCl 3 fraction of the aerial parts of Galphimia glauca. The biogenesis of the natural nor-triterpenes isolated from Galphimia glauca is delineated for the first time starting from the taraxasteryl cation. Oral administration of CHCl 3 fraction and 1-3 compounds produced significant attenuation in the anxiety-response in cylinder activity, decrease in the ambulatory activity and in head dipping when compared to the vehicle. However, only the extract enhanced the pentobarbital-induced hypnosis. Diazepam was used as a positive control., Conclusion: Our results suggest that G. glauca growing in Cuernavaca, Morelos, exerts anxiolytic-like activity due to the presence of the nor-triterpenes 1-3. These results reinforce the potential use of this species in the treatment of anxiety., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnobotanical field surveys revealed the use of fruits of Opuntia ficus indica (L.) Mill. for treating diabetes, burns, bronchial asthma, constipation, kidney stones, and rheumatic pains and as a sedative in Turkish folk medicine. This study aimed to verify the efficacy of the fruits of O. ficus indica experimentally and to define components responsible for the activity using bioassay-guided procedures. The crude methanolic extract of the fruits was sequentially fractionated into five subextracts: n -hexane, dichloromethane, ethyl acetate, n -butanol, and water. Further experiments were carried out on the most active subextract, that is, the ethyl acetate (EtOAc) subextract, which was further subjected to fractionation through successive column chromatographic applications on Sephadex LH-20. For activity assessment, each extract or fraction was submitted to bioassay systems; traction test, fireplace test, hole-board test, elevated plus-maze test, and open-field test were used for sedative and anxiolytic effects, and a thiopental-induced sleeping test was used for the hypnotic effect. Among the subextracts obtained from the methanolic extract, the EtOAc subextract showed significant sedative and anxiolytic effects in the bioassay systems. From the EtOAc subextract, major components were isolated, and their structures were determined as isorhamnetin, isorhamnetin 3- O -glucoside, isorhamnetin 3- O -rutinoside, and kaempferol 3- O -rutinoside using spectral techniques. In conclusion, this study confirmed the claimed use of the plant against anxiety in Turkish folk medicine.

Introduction: Peanut stems and leaves (PSL) have traditionally been used as both a special food and a herbal medicine in Asia. The sedative-hypnotic and anxiolytic effects of PSL have been recorded in classical traditional Chinese literature, and more recently by many other researchers. In a previous study, four sleep-related ingredients (linalool, 5-hydroxy-4',7-dimethoxyflavanone, 2'-O-methylisoliquiritigenin and ferulic acid), among which 5-hydroxy-4',7-dimethoxyflavanone and 2'-O-methylisoliquiritigenin were newly found in Arachis species, were screened by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS). In the current study, quantitative examination of the above four ingredients was conducted. Serious fundamental functional studies were done in mice, including locomotor activity, direct sleep tests, pentobarbital-induced sleeping time tests, subthreshold dose of pentobarbital tests and barbital sodium sleep incubation period tests, to determine the material base for the sedative-hypnotic and anxiolytic effects of aqueous extracts of PSL. Furthermore, neurotransmitter levels in three brain regions (cerebrum, cerebellum and brain stem) were determined using UHPLC coupled with triple-quadrupole mass spectrometry (UHPLC/QQQ-MS) in order to elucidate the exact mechanism of action., Results: Aqueous extract of PSL at a dose of 500 mg kg -1 (based on previous experience), along with different concentrations of the above four functional ingredients (189.86 µg kg -1 linalool, 114.75 mg kg -1 5-hydroxy-4',7-dimethoxyflavanone, 32.4mg kg -1 2'-O-methylisoliquiritigenin and 44.44 mg kg -1 ferulic acid), had a sedative-hypnotic effect by affecting neurotransmitter levels in mice., Conclusion: The data demonstrate that these four ingredients are the key functional factors for the sedative-hypnotic and anxiolytic effects of PSL aqueous extracts and that these effects occur via changes in neurotransmitter levels and pathways. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Background: Despite advances in the treatment of cardiovascular diseases in recent decades, patients experience high levels of depression, anxiety, stress, and insomnia. Since the calming effect of Melissa officinalis (MO) has been known, this study aimed to determine the effects of MO supplementation on depression, anxiety, stress, and sleep disturbances in patients with chronic stable angina (CSA)., Methods: In this double-blind placebo-controlled clinical trial, 80 patients with CSA were divided randomly into two groups (taking 3 g MO supplement or placebo daily for 8 weeks). The shortened 21-item version of the depression, anxiety and stress scale (DASS-21) test and Pittsburgh sleep quality index were done before and after the intervention., Results: At the end of the study, the intervention group receiving MO capsules had a significant reduction in scores of depression, anxiety, stress, and total sleep disturbance, compared with the placebo group (P < 0.05)., Conclusions: The results showed that 8-week supplementation with 3 g MO can decrease depression, anxiety, stress, and sleep disorder in patients with CSA., (Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: The superior genus Jacquemontia belongs to Convolvulaceae, with around 120 species, and is also considered taxonomically difficult. The aim of this experiment was to assess the sedative and hypnotic activities of methanol extract from the leaves of Jacquemontia paniculata (Burm.f.) Hallier f., Methods: The sedative and hypnotic activities were evaluated by hole-cross, open field, hole-board, elevated plus maze (EPM), and thiopental sodium-induced sleeping time determination tests in mice at doses of 200 and 400 mg/kg., Results: In this investigation, we found that methanol extract of Jacquemontia paniculata (MEJP) produced a significant dose-dependent inhibition of spontaneous activity of mice both in hole-cross and open field tests. In addition, it also decreased the number of head dips in hole-board test. In the case of EPM test, this crude extract induced an anxiogenic-like effect rather than anxiolytic effect in mice. Moreover, MEJP significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium., Conclusions: To conclude, these results suggest that the MEJP leaves possess potent sedative and hypnotic activities, which supported its therapeutic use for sleep disorders like insomnia.

Context: Myrtus communis L. (Myrtaceae), myrtle, is an evergreen shrub with strong antibacterial, anti-inflammatory, antihyperglycemic and antioxidant activities. Also, it is used as a sedative-hypnotic plant in Iranian traditional medicine., Objective: This study evaluates the effect of 80% ethanolic extract of M. communis leaves on sleep and anxiety in mice and rats., Materials and Methods: Male NMRI mice were subjected to open field, righting reflex, grip strength and pentylentetrazole-induced seizure tests. Male Wistar rats were used to evaluate the alterations in rapid eye movement (REM) and non-REM (NREM) sleep. They were treated with 25-400 mg/kg doses of the extract intraperitoneally., Results: The applied doses (50-200 mg/kg) of M. communis extract increased vertical (ED50 = 40.2 ± 6.6 mg/kg) and vertical and horizontal activity (ED50 = 251 ± 55 mg/kg), while treatment with 200 and 400 mg/kg attenuated muscle tone significantly compared to vehicle treated animals (p < 0.001 for all) in a dose-independent manner. Also, a significant hypnotic and not anticonvulsant effect was observed when animals were treated with 200 mg/kg of the extract (p < 0.01). In this regard, electroencephalography results showed that REM sleep time was decreased (2.4 ± 0.5%), while total and NREM sleep times were increased significantly compared to the control group of mice (82.5 ± 7.6%)., Discussion and Conclusion: The data show the anxiolytic and muscle relaxant effect of the extract without anticonvulsant activities. The anxiolytic, myorelaxant and hypnotic effects without effect on seizure threshold are in line with the effect of a alpha 2 GABA receptor agonist.

Ethnopharmacological Relevance: Tilia tomentosa Moench bud extracts (TTBEs) is used in traditional medicine for centuries as sedative compound. Different plants belonging to the Tilia genus have shown their efficacy in the treatment of anxiety but still little is known about the mechanism of action of their bud extracts., Aim of the Study: To evaluate the action of TTBEs as anxiolytic and sedative compound on in vitro hippocampal neurons., Material and Methods: The anxiolytic effect of TTBEs was assayed by testing the effects of these compounds on GABAA receptor-activated chloride current of hippocampal neurons by means of the patch-clamp technique and microelectrode-arrays (MEAs)., Results: TTBEs acutely administered on mouse hippocampal neurons, activated a chloride current comparable to that measured in the presence of GABA (100 µM). Bicuculline (100 µM) and picrotoxin (100 µM) blocked about 90% of this current, while the remaining 10% was blocked by adding the benzodiazepine (BDZ) antagonist flumazenil (30 µM). Flumazenil alone blocked nearly 60% of the TTBEs activated current, suggesting that TTBEs binds to both GABAA and BDZ receptor sites. Application of high-doses of TTBEs on spontaneous active hippocampal neurons grown for 3 weeks on MEAs blocked the synchronous activity of these neurons. The effects were mimicked by GABA and prevented by picrotoxin (100µM) and flumazenil (30 µM). At minimal doses, TTBEs reduced the frequency of synchronized bursts and increased the cross-correlation index of synchronized neuronal firing., Conclusions: Our data suggest that TTBEs mimics GABA and BDZ agonists by targeting hippocampal GABAergic synapses and inhibiting network excitability by increasing the strength of inhibitory synaptic outputs. Our results contribute toward the validation of TTBEs as effective sedative and anxiolytic compound., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Agastache mexicana subspecies mexicana (Amm) and xolocotziana (Amx) are used in Mexican traditional medicine to relief cultural affiliation syndromes known as "susto" or "espanto", for "nervous" condition, and as a sleep aid. Despite its intensive use, neuropharmacological studies are scarce, and the chemical composition of the aqueous extracts has not been described. Aims of the study are: (1) To analyze the chemical composition of aqueous extracts from aerial parts of Amm and Amx. (2) To evaluate the anxiolytic-like, sedative, antidepressant-like effects. (3) Analyze the general toxic effects of different doses., Materials and Methods: Anxiolytic-like and sedative effects were measured in the avoidance exploratory behavior, burying behavior and the hole-board tests. The antidepressant-like actions were studied in the forced swimming and tail suspension tests. Finally, general activity and motor coordination disturbances were evaluated in the open field, inverted screen and rota-rod tests. The acute toxicity of Amm and Amx was determined by calculating their LD50 (mean lethal dose). The chemical analyses were performed employing chromatographic, photometric and HPLC-ESI-MS techniques., Results: Low doses of Amm and Amx (0.1σ1.0mg/kg) induced anxiolytic-like actions; while higher doses (over 10mg/kg) induced sedation and reduced the locomotor activity, exerting a general inhibition in the central nervous system (CNS)., Conclusions: Results support the use of Amm and Amx in traditional medicine as tranquilizers and sleep inducers. Additionally, this paper contributes to the knowledge of the chemical composition of the aqueous extracts of these plants., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This study investigated the hypnotic, anti-convulsant and anxiolytic effects of 1-nitro-2-phenylethane (BPNE) obtained from the oil of Dennettia tripetala G. Baker (Annonaceae) and established its mechanism of action. The essential oil (EO) from the leaf, fruit and seed was obtained by hydrodistillation, followed by isolation of BPNE purified to 99.2% by accelerated gradient chromatography on silica, and identified by NMR and GC-MS. The pure BPNE and EO of the dried seed (93.6%) were comparatively evaluated for hypnotic, anticonvulsant and anxiolytic effects in mice. The acute toxicity of BPNE was determined and the LD50 was 490 mg/kg, intrapritonealy. The hypnotic activities of the EO and BPNE (50-400 mg/kg, i.p.) were assessed by loss of righting reflex, while sodium pentobarbitone (PBS) and diazepam (DZM) were used as positive controls. The anticonvulsant and anxiolytic effects of the EO and BPNE were evaluated in mice. Both BPNE and EO at doses ≥100 mg/kg induced spontaneous hypnosis with loss of righting reflex, significantly decreased sleep latency (SL) and also increased total sleeping time (TST) dose-dependently. They had comparable activity with NAP in TST. The BPNE exhibited higher hypnotic potency than EO at the same dose levels. The EO and BPNE offered comparable dose-related protections against PTZ- and strychnine-induced convulsions. Flumazenil (2 mg/kg) blocked the hypnotic and anticonvulsant (PTZ-convulsions) effects of both EO and BPNE. The essential oil at 5-20 mg/kg dose levels significantly (p<0.05) increased the percentage time spent and number of entries into the open arms. While at the same dose range BPNE significantly (p<0.05) increased the percentage time spent and the number of entries into the open arms respectively. The study concluded that 1-nitro-2-phenylethane exhibited dose dependent significant hypnotic, anticonvulsant and anxiolytic effects and it is the compound largely responsible for the neuropharmacological effects of the oil., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

The gamma-amino butyric acid (GABA) type A (GABA(A)) receptor represents a crucial target for clinical agents in the treatment of anxiety and insomnia. Using the two-microelectrode voltage clamp technique on recombinant α₁β₂γ(2S) GABA (A) receptors, effusol (1) and dehydroeffusol (2) were isolated in a bioactivity-guided approach from the pith of Juncus effusus L. Both compounds concentration-dependently enhanced GABA induced chloride currents (I(GABA)) by a maximum 188 ± 20 (1) and 239 ± 18 % (2), independent of the benzodiazepine (BZ) binding site. This activity on the GABA (A) receptor may explain the traditional use of J. effusus as a sedative and anxiolytic agent in Chinese medicine., (© Georg Thieme Verlag KG Stuttgart · New York.)

This study evaluated possible CNS effects of a hexane extract of leaves from Rollinia mucosa (Jacq.) Baill. (Annonaceae). This plant extract induced anxiolytic-like actions similar to those induced by diazepam in the avoidance exploratory behavior paradigm. Its significant activity was shown at doses from 1.62 to 6.25 mg/kg. It also enhanced pentobarbital-induced hypnosis time, and at high doses produced motor coordination impairment. The benzodiazepine (BDZ) receptor binding, evaluated by in vitro autoradiography following a single administration of R. mucosa, revealed that this plant extract reduced BDZ binding in the hippocampus (29%), amygdala (26%), and temporal cortex of mice (36%). In conclusion, the present findings support the proposal that R. mucosa may induce central nervous system (CNS) depressant effects, presumably through an interaction with the GABA/benzodiazepine receptor complex.

Citrus aurantium L. is commonly used as an alternative treatment for insomnia, anxiety and epilepsy. Essential oil from peel (EOP) and hydroethanolic (70% w/v) extract (HE) from leaves were obtained. Hexanic (HF), dichloromethanic (DF) and final aqueous (AF) fractions were obtained from HE by successive partitions. Swiss male mice (35-45 g) were treated orally with 0.5 or 1.0 g/kg of these preparations 30 min before the experiments for the evaluation of the sedative/hypnotic activity (sleeping time induced by sodium pentobarbital - SPB: 40 mg/kg, i.p.), anxiolytic activity (elevated plus maze--EPM) and anticonvulsant activity (induced by pentylenetetrazole--PTZ: 85 mg/kg, sc or by maximal electroshock--MES: 50 mA, 0.11 s, corneal). The results showed that EOP (0.5 g/kg) increased the latency period of tonic seizures in both convulsing experimental models. This effect was not dose-dependent. Treatment with 1.0 g/kg increased the sleeping time induced by barbiturates and the time spent in the open arms of the EPM. Specific tests indicated that the preparation, in both doses used, did not promote deficits in general activity or motor coordination. HF and DF fractions (1.0 g/kg) did not interfere in the epileptic seizures, but were able to enhance the sleeping time induced by barbiturates. The results obtained with EOP in the anxiety model, and with EOP, HF and DF in the sedation model, are in accord with the ethnopharmacological use of Citrus aurantium L., which could be useful in primary medical care, after toxicological investigation.