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Background: Veterinary drugs are widely used in animal production to prevent infections and treat diseases but, this may cause a risk to consumers. Due to the high number of food samples required to monitor yearly, simple, fast, sensitive and selective analytical methods are needed in control laboratories to ensure consumers safety. Nevertheless, many analytical methodologies available in these laboratories include multiple steps and therefore are time-consuming and hinder the analysis throughput requiring significant amounts of solvents and reagents., Results: This work developed a 96-well plate solid phase extraction (SPE) method for the extraction of seven sedatives and a β-blocker in animal kidney by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The developed method was validated based on Implementing Regulation (EU) 2021/808 in kidney, meat and fish. The performance characteristics of the validation (1-5 μg kg -1 ) showed good linearity (R 2  > 0.998) while decision limits (CCα) were between 1 and 1.2 μg kg -1 . Trueness and precision were determined at three levels (n = 7) and the results showed values ranging from 85 to 103 % and from 1 to 9 %, respectively. The feasibility of the method was demonstrated for the residue control requirement established by EU. Method was applied to 201 samples of kidney, meat and fish., Significance: This study is the first to present an optimized and validated holistic method for sedatives and β-blocker using 96-well plate SPE and UHPLC-MS/MS. The method showed good performance in kidney, meat and fish samples being an universal method for any species along the same type of sample. The fast, easy, efficient, reliable and universal method showed high throughput and so reduced the analysis time by nine-fold and the required solvent amount by four times fulfilling the green chemistry principals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Mulberry leaf (Folium Mori) is a dried leaf of the dicotyledonous mulberry tree and is a homologous food and medicine. Treating insomnia with it is a common practice in traditional Chinese medicine. But still, its potential sleep-improving mechanism remains to be elucidated., Aim of Review: Potential bioactive components and mechanisms of the sleep-improving effect of purified flavone from mulberry leaves (MLF) were explored through in vivo experiments, network pharmacology analysis, and molecular experimental validation., Materials and Methods: The mice model was established by pentobarbital sodium induction to evaluate the sleep-improving effect of MLF. The MLF's chemical composition was identified through a liquid chromatograph quadrupole time-of-flight mass spectrometer (Q-TOF LC/MS) to elucidate its sleep-improving active ingredient. At last, the underlying mechanism of MLF's sleep-improving effect was elucidated through neurotransmitter detection (ELISA), network pharmacology analysis, and molecular experimental validation (quantitative real-time PCR and western blotting)., Results: MLF could dramatically reduce sleep latency by 35%, prolong sleep duration by 123%, and increase the sleep rate of mice through increasing γ-aminobutyric acid (GABA) and serotonin (5-HT) release in serum, hypothalamus, and hippocampus. Q-TOF LC/MS identified 17 flavonoid components in MLF. Network pharmacological analysis suggested that the key sleep-improving active ingredients in MLF might be quercetin, kaempferol, morin, and delphinidin. The key path for MLF to improve sleep might be the tryptophan metabolism and neuroactive ligand-receptor interaction, and the key targets might be gamma-aminobutyric acid type A receptor subunit alpha2 Gene (GABRA2) and serotonin 1A (5-HT1A) receptors., Conclusions: MLF has shown significant sleep-improving effects in mice and may take effect through regulating the GABA and 5-HT receptors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Atractylis aristata batt., as an endemic plant from the Asteraceae family, holds a significant position in the Ahaggar region of southern Algeria's traditional medicine. The aerial parts of Atractylis aristata was used to cure inflammation, fever, and stomach disorders., Aim of the Study: The objective of the present investigation was to ascertain the overall bioactive components and phytochemical components and examine the antioxidant, antidiabetic, anti-inflammatory, acute toxicity, and sedative properties of the crude extract obtained from the aerial portions of Atractylis aristata (AaME)., Materials and Methods: The AaME's antioxidant activity was assessed by the use of pyrogallol autoxidation, (1,1 diphenyl-2-picrylhydrazyl) (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power (RP) techniques. 1 mg/mL of AaME was used to evaluate the antidiabetic activity by applying the enzyme α-amylase inhibitory power test. At the same time, the bovine serum albumin (BSA) denaturation method was employed to quantify the in vitro anti-inflammatory activity at different concentrations (1.5625, 0.78125, 0.390625, 0.1953125 and 0.09765625 mg/mL). In contrast, following the Organization for Economic Co-operation and Development (OECD) guideline No. 423, which covers acute oral toxicity testing protocols, the limit dosage test was employed to assess in vivo acute toxicity. At the dose of 0.08 mg/mL, the carrageenan-induced paw edema approach was used to assess the anti-inflammatory efficacy in vivo, and the sedative activity was carried out at the dose of 0.08 mg/mL using the measurement of the locomotor method. Different bioactive compounds were identified within AaME using LC-MS/MS and HPLC-UV analysis., Results: The acute toxicity study showed no fatalities or noticeable neurobehavioral consequences at the limit test; this led to their classification in Globally Harmonized System (GHS) category Five, as the OECD guideline No 423 recommended. At a concentration of 0.08 mg/mL (2000 mg/kg), AaME showed apparent inhibition of paw edema and a significant (p = 0.01227) reduction in locomotor activity compared to the control animals. Our findings showed that AaME exhibited considerable antioxidant (IC 50  = 0.040 ± 0.003 mg/mL (DPPH), IC 50  = 0.005 ± 5.77 × 10-5 mg/mL (ABTS), AEAC = 91.15 ± 3.921 mg (RP) and IR% = 23.81 ± 4.276 (Inhibition rate of pyrogallol) and rebuts antidiabetic activities (I% = 57.6241% ± 2.81772). Our findings revealed that the maximum percentage of BSA inhibition (70.84 ± 0.10%) was obtained at 1.562.5 mg/mL. Thus, the AaME phytochemical profile performed using phytochemical screening, HPLC-UV, and LC-MS/MS analysis demonstrated that A. aristata can be a valuable source of chemicals with biological activity for pharmaceutical manufacturers., Conclusion: The phytochemical profiling, determined through HPLC-UV and LC-MS/MS applications, reveals this plant's therapeutic value. The aerial parts of Atractylis aristata contain bioactive molecules such as gallic acid, ascorbic acid, and quercetin, contributing to its significant antioxidant capabilities. Furthermore, identifying alizarin, the active compound responsible for its anti-inflammatory properties, could provide evidence supporting the anti-inflammatory capabilities of this subspecies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Traditional Chinese medicine believes that depression syndrome has become one of the core pathogenesis of insomnia. The pharmacology of traditional Chinese medicine points out that Perilla frutescens has the effect of regulating Qi and relieving depression, promoting Qi circulation to relieve pain, so Perilla frutescens may have the potential therapeutic effect on insomnia. Related studies have reported the sedative and hypnotic effects of Perilla frutescens, but these studies have not yet explored the mechanism of sedative and hypnotic effects of Perilla frutescens essential oil (PFEO) through inhalation administration., Aim of the Study: The purpose of this study is to explore the underlying sedative and hypnotic mechanisms of PFEO through the GABAergic system pathways., Materials and Methods: Established the PCPA insomnia model of mice, The open field test, pentobarbital-induced falling asleep rate, latency of sleeping time, and duration of sleeping time experiments were used to evaluate the behavior of mice, the enzyme-linked immunosorbent assay was used to analyze the content of 5-HT and GABA in hypothalamus and cerebral cortex. Immunohistochemical experiment, Western blot experiment and RT-PCR experiment were used to study the mechanism of PFEO through GABAergic pathway to regulate insomnia. The main volatile constituents of PFEO were analyzed by gas chromatography-mass spectrometry (GC-MS)., Results: The inhalation of PFEO has sedative and hypnotic effects, which reduce significantly the autonomic activity of PCPA insomnia mice, increase falling asleep rate, shorten latency of sleeping time, and prolong duration of sleeping time; the results of enzyme-linked immunosorbent assay show that PFEO increase the content of 5-HT and GABA in hypothalamus and cerebral cortex. The results showed that inhalation of PFEO increase the expression of GABAAα1 and GABAAα2 positive cells, increase the level of GABAAα1 and GABAAα2 protein and also increase the level of GABAAα1 mRNA and GABAAα2 mRNA in the hypothalamus and cerebral cortex. The highest content of PFEO is Perillaldehyde (54.37%), followed by 1,4-Cineole (7.42%), Acetaldehyde diethyl acetal (6.61%), D-Limonene (5.09%), Eucalyptol (4.94%), etc. CONCLUSION: The inhalation of PFEO has sedative and hypnotic effects, it is speculated that the mechanism of which may be the sedative and hypnotic effects through the GABAergic pathway., (Copyright © 2020 Elsevier B.V. All rights reserved.)

About 30% of epileptic patients continue to have seizures. The present study investigates the anticonvulsant and sedative effects of an aqueous extract of C. schweinfurthii in mice. Anticonvulsant effects of C. schweinfurthii aqueous extract (0.01-300 mg/kg, p.o.) were tested against 4-aminopyridine (4-AP, 15 mg/kg, i.p.) -, pilocarpine (PILO, 380 mg/kg, i.p.) - and pentylenetetrazole (PTZ, 75 mg/kg, i.p.) -induced seizures, while sedative effects were tested on diazepam (35 mg/kg, i.p.)-induced sleep. Afterward, the most effective dose of the extract (11.9 mg/kg) was antagonized with N-methyl-β-carboline-3-carboxamide or flumazenil. In another set of experiments, mice were sacrificed for the estimation of GABA content and GABA-T activity in the cerebral cortex. The dose of the extract that protected 50% of mice (ED 50 ) against 4-AP, PILO, and PTZ was respectively 4.43 mg/kg (versus 12.01 for phenobarbital), 9.59 mg/kg (vs 8.67 for diazepam), and 2.12 mg/kg (vs 0.20 for clonazepam). Further, the ED 50 of the extract that increased the duration of sleep was 0.24 mg/kg (vs 0.84 for phenobarbital). N-methyl-β-carboline-3-carboxamide or flumazenil antagonized (p < 0.001) the anticonvulsant effect of C. schweinfurthii in PTZ-induced seizures and diazepam-induced sleep when compared to the negative control group. The extract at all doses increased (p < 0.001) the GABA content and decreased (p < 0.001) GABA-T activity. These findings suggest that C. schweinfurthii possesses anticonvulsant and sedative effects. These effects seem to be mediated via the modulation of the GABA neurotransmission. These data explain the use of this plant to treat epilepsy in Cameroon traditional medicine., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Agarwood is known to have a sedative effect and the less studied volatile aromatic constituents it contains may have contribution to the activity. In this study, two Kyara grade (highest-grade agarwood in Japan) samples were extracted using headspace-solid phase microextraction (HS-SPME) and analyzed through gas chromatography-mass spectrometry (GC-MS). Six low molecular weight aromatic compounds (LACs) and one structurally simple compound (diethylene glycol monoethyl ether) present in the aromas were individually evaluated for inhalational sedative activity in mice through open field test. Doses of 0.0001 g/L to 1 g/L were prepared for each compound and administered to mice ( n = 6/dose/compound). Results revealed all compounds decreased spontaneous motor activity at almost all doses. Strongest sedative activity of each compound reduced total spontaneous motor activity by more than half against control, demonstrating their contribution to agarwood aroma and potential as independent sedating agents. Mixtures of compounds using their most effective dose were made and evaluated again for inhalational sedative effect. Interestingly, the combination of all compounds showed no significant effect and even caused stimulation in mice movements. This result suggests antagonistic-like interaction between the compounds, which is probably due to structural similarities. Consequently, it implies the other constituents present in agarwood, along with LACs, are also important to the overall sedative activity.

Background: Sleep disorders are among the most common psychiatric and medical conditions. Herbal medicine appears to be effective in the treatment of sleep disorders which have been valued by many of publications and patents., Objective: The present study aimed at investigating the hypnotic activity of the hydro-alcoholic extract of Capparis spinosa (HAE) in mice., Methods: Three doses of HAE (30, 60 and 120 mg/kg) and three fractions of it, namely n-hexane fraction (NHF), water fraction (WF), and ethyl acetate fraction (EAF), were given in comparison with diazepam (3 mg/kg body weight i.p.) as a positive control and saline as a negative control. After 30 min, pentobarbital (30 mg/kg body weight i.p.) was administered. In addition, LD50 of HAE was examined and the cytotoxicity of HAE was assessed in l929 cells using the MTT assay. Moreover, for motorcoordination ability, 30 mins after administration of HAE, the rotarod test was performed., Results: The results exhibited that the HAE and all the fractions significantly augmented pentobarbital induced sleeping time, which was comparable to that of induced by diazepam. The LD50 value was 2.4 g/kg. The extract did not induce any cytotoxic effects in L929 fibroblast cells. HAE did not affect the animals' performance on the rotarod test., Conclusion: Our finding suggests that the hydro-alcoholic extract of C. spinosa possesses a hypnotic potential that may require further scientific investigations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ethnopharmacological Relevance: Lingzhi or Reishi - Ganoderma lucidum (Fr.) P. Karst is an extensively used medicinal mushroom in folklore and traditional medicine in south East Asia to treat a number of diseases. Lingzhi is known as 'mushroom of immortality' in Chinese folklore. In Traditional Chinese Medicine it is considered as a panacea to cure all diseases., Aim of the Study: This study aims to evaluate antinociceptive effect of Gano oil, a novel fatty acid rich extract obtained from G. lucidum and identification of the active principle., Materials & Methods: Gano oil extracted from Ganoderma lucidum was evaluated for inhibition of formalin-induced paw oedema on Swiss albino mice by oral administration as well as topical application. Antinociceptive activity of Gano oil was tested by acetic acid - induced abdominal writhing test as well as hot plate test. Free radical scavenging activity was determined by DPPH assay. COX enzyme inhibiting activity was assayed using different concentrations of Gano oil exposed to LPS stimulated RAW 264.7 cell line. NF-kB inhibiting activity of Gano oil was assayed using Lentix-293T P65 Ds Red stable cell line by fluorescent imaging and flow cytometry analysis. Chemical profile of Gano oil was ascertained by HPTLC analysis and active principle was identified by HRLCMS analysis., Results: The oral administration of Gano oil at doses of 10,25, 50 mg/kg b.wt showed 42, 58 and 73% inhibition of paw oedema while topical applications at dose of 1,5 and 10% reduced 33, 50 and 58% oedema respectively. Acetic acid writhing test showed that Gano oil inhibited 44.44% contortions (p < 0.001) and while in hot plate method Gano oil at 25 mg/kg b. wt showed response latency of 30.0 ± 2.08 s for 120 min compared to base 1.65 ± 0.32 s (p < 0.01). Gano oil at 100 μg/ml inhibited 50% COX enzyme activity (p < 0.01). High throughput flurescent imaging and flow cytometry assay revealed marked ability of Gano oil to inhibit NF-kB activity. Gano oil was found to possess dose dependent free radical scavenging activity as evident from DPPH assay. HPTLC analysis of Gano oil indicated the chemical figure print. HR LC-MS analysis showed the major chemical components were fatty acid amides namely, Oleamide, C 18 H 35 NO, M + 281, Hexadecanamide, C 16 H 33 NO, M + 255 and 9-oxo-10 (E) Octadecadienoic acid, C 18 H 30 O 3 M + 294., Conclusion: Fatty acid rich Gano oil extracted from G.lucidum is a novel antinociceptive agent capable to inhibit oedema by oral administration as well as topical application. The results indicate the pharmacological interest, clinical significance and therapeutic use. The finding suggests that Gano oil might be a potent natural product based analgesic. The effect might be assigned to the fatty acid amide constituents especially oleamide which has been demonstrated to have analgesic and hypnotic actions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Traditional Persian Medicine (TPM) has been established as a valuable source of medicinal plants for the treatment of insomnia for thousands of years. Accordingly, oil extracts from plants' parts have been widely used to alleviate central nervous system (CNS) ailments including sleep disorders. A number of preparations have been recommended by TPM for the treatment of insomnia. Among them, an intranasal formulation containing oily macerates of Viola odorata L., Crocus sativus L. and Lactuca sativa L. stands out., Aim of the Study: In the present double-dummy, double-blind placebo controlled clinical trial, we aim to evaluate the effectiveness of a combination of violet oil, saffron oil, and lettuce seeds oil nasal drop compared with the placebo (sesame oil)., Materials and Methods: Fifty patients with primary chronic insomnia were randomly assigned in TPM-treatment or placebo groups, received either two drops of the herbal oil or placebo into each nostril every noon and evening for 8 weeks. Before the study commencement and after 1, 4 and 8 weeks of treatment, Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires were completed by all patients. The primary outcome measure was considered as any changes in ISI scores between the first visit and after 8 weeks. Changes in PSQI scores during the study and possible side effects were also assessed. The multicompound herbal oil was standardized using HPLC analysis and contained 0.02 mg/mL crocin and 4 μg/mL isoquercitrin., Results: Our study revealed a significant reduction in the ISI and PSQI scores from baseline by the study endpoint (P ≤ 0.01). The mean ISI scores in week 8 decreased significantly for the intervention group (P = 0.001) and also the placebo group (P < 0.01) when compared with baseline. Moreover, the use of hypnotic drugs in the intervention group was significantly reduced (P < 0.001), while in the control group was maintained at baseline level., Conclusions: It seems that intranasal use of the multi-herbal preparation can be used to improve chronic insomnia and to reduce the dose of conventional hypnotic medications in insomniac patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of this study was to develop a new approach to sample preparation of biological material based on a combination of the Dried Blood Spot (DBS) method and capillary electrophoresis coupled with mass spectrometry (CE-MS) for the analysis of blood samples collected in vivo or post-mortem. The proposed approach allowed the identification of typical drugs from different groups, such as tricyclic antidepressants (amitriptyline, imipramine), selective serotonin reuptake inhibitors (citalopram), benzodiazepines (tetrazepam) and hypnotics (zolpidem). In this study, a blood sample was spotted on FTA DMPK C cards, then dried, and 6-mm discs were cut out. The sample preparation procedure involved microwave-assisted extraction (MAE). Various extraction agents, temperatures and durations of extraction were examined in order to achieve the highest efficiency of the process. The method was subjected to a validation procedure. Limits of detection (LOD = 1.76 - 14.7 ng/mL) and quantification (LOQ = 5.25 - 49.0 ng/mL), inter- (CV = 1.31 - 9.43%) and intra- (CV = 3.26 - 18.52%) day precision of the determinations, recovery (RE = 85.0-105.4%) and matrix effect on ionization of analytes (ME = 98.6-105.5%) were determined. Furthermore, the developed DBS/MAE/CM-MS method was selective and analytes present in the blood applied on DBS cards were found to be stable after 7 and after 14 days. Moreover, the developed method was successfully applied to the analysis of both post-mortem samples and blood samples taken from patients treated with the analyzed drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.)

Rationale: Sedatives, which are prone to cause residues in animals, have been abused in modern animal husbandry. Long-term consumption of contaminated meat products would be unfavorable to the human nervous system. Taking into account public health and food safety, it was essential to develop an effective method for the enrichment and detection of sedatives in meat., Methods: Fe 3 O 4 @TbBd@ZIF-8 composites were synthesized by using Fe 3 O 4 nanoparticles as a magnetic core and 1,3,5-triformylbenzene (Tb) and benzidine (Bd) as two building blocks to form Fe 3 O 4 @TbBd. Furthermore, the zeolitic imidazolate framework-8 (ZIF-8) was modified on the surface of the Fe 3 O 4 @TbBd. In addition, Fe 3 O 4 @TbBd@ZIF-8 was used as a magnetic solid-phase extraction (MSPE) adsorbent of typical animal sedatives in pork samples. Mass spectrometry analysis was conducted by electrospray ionization triple-quadrupole mass spectrometry in positive-ion multiple reaction monitoring mode., Results: By combining the optimized MSPE approach with high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS), an accurate and sensitive method for the determination of sedatives was developed. The method exhibited good linearity in the range of 0.03-70 μg/kg with the correlation coefficient (R 2 ) ranging from 0.9982 to 0.9999, high sensitivity with limits of detection (LODs) ranging from 0.04 to 0.2 μg/kg, and high precision with relative standard deviation (RSD) less than 5.5%. The adsorption behaviors of Fe 3 O 4 @TbBd@ZIF-8 towards sedatives were more suitably described by a pseudo-second-order kinetic and Freundlich isotherm model., Conclusions: The proposed MSPE-HPLC/MS/MS method was successfully applied to the determination of sedatives in real samples and showed excellent applicability. Several sedatives were detected in the selected meat samples. The developed method was shown to be facile, sensitive and accurate for sedative detection and also showed great prospects for determination of sedatives from other complex samples., (© 2020 John Wiley & Sons, Ltd.)

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.

Lactuca L. species belong to the Asteraceae family and these plants are traditionally used for therapeutic purposes around the world. The dried milky latex of L. serriola is known as "lettuce oil" and is used as a sedative in Turkey. This study aimed to evaluate the sedative effects and analyze the chemical compositions of latexes obtained from some Lactuca species growing in Turkey. The sedative effects were evaluated through various behavioral tests on mice. For this purpose, latexes were obtained from L. glareosa Boiss., L. viminea (L.) J. Presl and C. P, L. mulgedioides (Vis and Panćić) Boiss. and Kotschy ex. Boiss., L. saligna L., and L. serriola L. The latex from L. saligna showed the highest sedative effects, whilst L. serriola and L. viminea latexes also displayed significant sedative effects compared to the control group at a dose of 100 mg/kg. However, the latexes from L. glareosa and L. mulqedioides did not exhibit any sedative effects on mice. Characteristic sesquiterpene lactones (lactucin, lactucopicrin, 11,13β-dihydrolactucin, and 11,13β-dihydrolactucopicrin) were determined qualitatively and quantitatively by high-performance liquid chromatography (HPLC). Lactucin was identified as the main component.

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lack of a safe and convenient disposal method for expired and unused medications may lead to many problems such as accidental exposure, intentional misuse, and food and water contamination. Activated carbon can offer safe disposal of medications due to its highly porous structure, which exerts strong physical adsorption forces with chemicals. This study aimed to evaluate the efficiency of an activated carbon-based drug disposal system for deactivating three model sedative prescription medications. Deactivation was performed by mixing the medication, activated carbon, and tap water. Desorption was evaluated by exposing the deactivation system to wash-out solutions. Rapid, precise, accurate, and sensitive HPLC-UV method for each drug was successfully developed, validated and employed. Results of the 28-day deactivation study showed that on average, more than 94.00% of drugs were rapidly deactivated within 8 hours. All drugs reached more than 99.00% deactivation by the end of 28-day period. Desorption study demonstrated that all medications were retained by the system, with insignificant amount of drug (0.25%) leached into the washout solutions within 24 hours. In conclusion, activated carbon rapidly and successfully deactivated the medications tested, suggesting activated carbon-based drug disposal system provides a convenient, secure, and effective method for unused medication.

Studies using silver catfish (Rhamdia quelen) as experimental models are often applied to screen essential oils (EO) with GABAergic-mediated effects. However, the expression of GABAa receptors in the silver catfish brain remains unknown. Thus, we assessed whether silver catfish express GABAa receptor subunits associated with sedation/anesthetic process and/or neurological diseases. Additionally, we evaluated the brain expression of GABAa receptor subunits in fish sedated with Nectandra grandiflora EO and its isolated compounds, the fish anesthetic (+)-dehydrofukinone (DHF), and dehydrofukinone epoxide (DFX), eremophil-11-en-10-ol (ERM) and selin-11-en-4-α-ol (SEL), which have GABAa-mediated anxiolytic-like effects in mice. The expression of the subunits gabra1, gabra2, gabra3, gabrb1, gabrd and gabrg2 in the silver catfish brain were assessed after a 24h-sedation bath by real time PCR. Since qPCR data rarely describes mechanisms of action, which are usually found through interactions with receptors, we also performed an antagonist-driven experiment using flumazenil (FMZ). Real-time PCR detected the mRNA expression of all targeted genes in R. quelen brain. The expression of gabra1 was decreased in fish sedated with ERM; EO increased gabra2, gabra3, gabrb1 and gabrg2 expression; SEL increased gabrb1, gabrd and gabrg2 expression. EO and compounds DFX, SEL and ERM induced sustained sedation in fish and FMZ-bath prompted the recovery from ERM- and DFX-induced sedation. Our results suggest that the EO, SEL, ERM and DFX sedative effects involve interaction with the GABAergic system. Our findings support the use of the silver catfish as robust and reliable experimental model to evaluate the efficacy of drugs with putative GABAergic-mediated effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cinnabar is an attractive mineral with many different uses. It is reported that cinnabar is one of the traditional Chinese's medicines extensively use. The main objective of this critical review is to identify the current overview, concept and chemistry of cinnabar, which includes the process developments, challenges, and diverse options for pharmacology research. It is used as a medicine through probable toxicity, especially when taking overdoes. This review is the first to describe the toxicological effects of cinnabar and its associated compounds. Nuclear magnetic resonance (NMR) dependent metabolomics could be useful for examination of the pharmaceutical consequence. The analysis indicated that the accurate preparation methods, appropriate doses, disease status, ages with drug combinations are significant factors for impacting the cinnabar toxicity. Toxicologically, synthetic mercury sulfide or cinnabar should be notable for mercuric chloride, mercury vapor and methyl mercury for future protection and need several prominent advancements in cinnabar research.

Insomnia is a state defined as trouble with sleep; it is a chronically disabling condition and is now significantly prevalent, imposing enormous health and economic burdens both on individuals and on society. This state includes trouble in falling asleep, problems staying asleep, fragmented sleep (repeatedly awakening at night), and/or awakening before time in the morning. This difficulty in sleeping causes feeling exhausted during the day and trouble with daytime activities including driving, family responsibilities, and completion of valued daily routines. Different types of synthetic sedative drugs are used to handle nervous system changes, but repeated use of sedatives caused tolerance in the human body. After a while, people had to take a heavy dose of sedative to make them feel sleepy, which imposes extra toxic effects on vital organs of the body. Medicinal plants are gaining more and more attention as sedative agents because herbs contained different types of natural bioactive metabolites with not well reported side effects. In addition, medicinal plants have economic, high efficacy and are easy available. So in current review plants possessing sedative activities have been compiled with their constituents responsible to manage insomnia. Review of the literature indicated that medicinal plants from various systems of medicine have been reported to possess sedative activity. This review suggests that medicinal plants are efficacious for insomnia; further laboratory and clinical studies are required.

Galphimia glauca is a plant that is endemic to Mexico and has been commonly used since pre-Hispanic times to treat various illnesses, including central nervous system disorders and inflammation. The first studies investigating a natural population of G. glauca in Mexico showed that the plant has anxiolytic and sedative activities in mice and humans. The plant's bioactive compounds were isolated and identified, and they belong to a family of nor-secofriedelanes called galphimines. The integration of DNA barcoding and thin-layer chromatography analysis was performed to clarify whether the botanical classification of the populations in the study, which were collected in different regions of Mexico, as G. glauca was correct or if the populations consist of more than one species of the genus Galphimia. We employed six DNA barcodes (matK, rbcL, rpoC1, psbA-trnH, ITS1 and ITS2) that were analyzed individually and in combination and then compared each other, to indicate differences among the studied populations. In the phylogenetic analysis, ITS1 and ITS2 markers as well as the combination of all DNA regions were the most efficient for discriminating the population studied. The thin-layer chromatography analysis exhibited four principal chemical profiles, one of which corresponded to the populations that produced galphimines. DNA barcoding was consistent and enabled us to differentiate the populations that produce galphimines from those that do not. The results of this investigation suggest that the studied populations belong to at least four different species of the genus Galphimia. The phylogenetic analysis and the thin-layer chromatography chemical profiles were convenient tools for establishing a strong relationship between the genotype and phenotype of the studied populations and could be used for quality control purposes to prepare herbal medicines from plants of the genus Galphimia., Competing Interests: The authors have declared that no competing interests exist.

The study is conducted to observe and investigate the effects of oral dosing of methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) on neuropharmacological activities of mice. Methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) were soluble in Dimethyl sulphoxide (DMSO) i.e. an organic solvent, so it is used in this study. Screening for anxiolytic and antidepressant effects were performed using open field test, head dip test, stationary rod test, cage crossing test, light and dark box and swimming- induced depression test. Thirty animals were divided into three groups of 10 animals each and numbered as 1 (control, on DMSO), 2(on methanolic extract of Cuminum nigrum (L), 3 (on methanolic extract of Centratherum anthelminticum (L). The extracts and DMSO were administered orally for 60 days. Any possible change in animal behavior was evaluated on day 15, 30 and 60 of dosing. The groups 2 and 3 showed significant increase (p<0.001, p<0.01) in open field activity and light and dark box test respectively, while significantly decreased activity was observed in head dip and cage crossing activity (p<0.01) after 60 days of dosing. Based on above findings, it is suggested that the extracts of Centratherum anthelminticum (L) and Cuminum nigrum (L) have antidepressant and anxiolytic potential with sedative effects.

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.)

Benzodiazepines (BZD) and Z-hypnotics are frequently analyzed in forensic laboratories, and in 2012, the designer benzodiazepines (DBZD) emerged on the illegal drug scene. DBZD represent a particular challenge demanding new analytical methods. In this work, parallel artificial liquid membrane extraction (PALME) is used for sample preparation of DBZD, BZD, and Z-hypnotics in whole blood prior to UHPLC-MS/MS analysis. PALME of BZD, DBZD, and Z-hypnotics was performed from whole blood samples, and the analytes were extracted across a supported liquid membrane (SLM) and into an acceptor solution of dimethyl sulfoxide and 200 mM formic acid (75:25, v/v). The method was validated according to EMA guidelines. The method was linear throughout the calibration range (R 2  > 0.99). Intra- and inter-day accuracy and precision, as well as matrix effects, were within the guideline limit of ± 15%. LOD and LLOQ ranged from 0.10 to 5.0 ng mL -1 and 3.2 to 160 ng mL -1 , respectively. Extraction recoveries were reproducible and above 52%. The method was specific, and the analytes were stable in the PALME extracts for 4 and 10 days at 10 and - 20 °C. No carry-over was observed within the calibration range. PALME and UHPLC-MS/MS for the determination of DBZD, BZD, and Z-hypnotics in whole blood are a green and low-cost alternative that provides high sample throughput (96-well format), extensive sample clean-up, good sensitivity, and high reproducibility. The presented method is also the first method incorporating analysis of DBZD, BZD, and Z-hypnotics in whole blood in one efficient analysis. Graphical abstract.

The aim of this study was to investigate the sedative activity of the aqueous leaf extract of Passiflora quadrangularis, a species that is widely cultivated and consumed in South America, and to identify its main constituents and elucidate the involvement of the GABAergic pathway in its mechanism of action. The bioguided fractionation of the crude extract showed a positive relationship between the sedative activity of the extract and its flavonoids. The methods employed to identify and isolate its main flavonoids resulted in the identification of vitexin-2''-O-xyloside, vitexin-2''-O-glucoside, orientin-2''-O-xyloside and orientin-2''-O-glucoside. Vitexin-2"-O-xyloside, the major flavonoid of the extract, showed sedative activity after oral administration in mice., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The aim of this study was to investigate the beneficial effect of Valerian/Cascade mixture on sleeping in mammal models. In pentobarbital-induced sleep model, Valerian, Cascade, and Valerian/Cascade mixture significantly reduced the latency time for sleeping, and total sleeping time effectively increased in these sample groups compared with the control. Valerian/Cascade mixture increased sleep duration by 37%. The mixture significantly increased the non-rapid eye movement (NREM) sleep time by 53% compared with the control, while REM sleeping time was decreased by 33% with Valerian/Cascade mixture, in Electroencephalography (EEG) analysis, resulting in the increase of total sleep time and the decrease of awakening. This sleep-promoting effect was obvious in caffeine-induced awakening model; Valerian, Cascade, and the mixture significantly enhanced NREM and total sleep time, which were reduced by caffeine. Caffeine-induced increase of awakening was effectively deceased to the normal level by these three samples. In particular, delta wave responsible for deep sleep in NREM was greatly increased by the mixture in both normal and caffeine-induced awake models. This sleep-promoting effect of Valerian/Cascade mixture was shown to be due to the upregulation of gamma-aminobutyric acid A receptor (GABA A R). Valerian/Cascade mixture showed 91% binding capacity to GABA A -BZD receptor. Two compounds, Valerenic acid and Xanthohumol, were shown to significantly contribute to the binding activity of Valerian/Cascade mixture on the GABA receptor., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Two new sesquiterpenes, trivially named ricinusoids A (1) and ricinusoids B (2), were isolated from ethyl acetate fraction of Ricinus communis. The structures of new compounds were elucidated by detailed spectroscopic techniques, including 1D- and 2D-NMR, UV, IR spectroscopy, and mass spectrometry. The compounds (1-2) were also assessed for in-vivo sedative and analgesic like effects in open field and acetic acid induced writhing tests respectively at 5, 10, and 20 mg·kg -1 i.p. Pretreatment of both test compounds caused significant (P ≤ 0.05) reduction in locomotive activity like sedative agents and abdominal constrictions like analgesics. Both compounds (1-2) possessed marked sedative and antinociceptive effects in animal models., (Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Context: Papaver rhoeas L. (Papaveraceae) corn poppy, widely distributed in Turkey, is used to make a cough syrup for children, as a tea for disturbed sleep, for pain relief and as a sedative in folk medicine., Objective: Samples of P. rhoeas collected from eight different locations in Turkey and three from northern Cyprus were investigated for their alkaloid content and screened for their antimicrobial activities., Materials and Methods: From the aerial parts of P. rhoeas samples, alkaloids were isolated by column and preparative thin-layer chromatography. The alkaloids were identified by comparing their spectral data (UV, IR and 1 H-NMR) and TLC Rf values with those of authentic samples. The antimicrobial study was carried out by microbroth dilution technique against six strains of bacteria and three strains of fungi., Results: Twelve different alkaloids belonging to proaporphine (mecambrine), aporphine (roemerine), promorphinan (salutaridine), protopine (coulteropine and protopine) and rhoeadine (epiglaucamine, glaucamine, glaudine, isorhoeadine, isorhoeagenine, rhoeadine and rhoeagenine) groups were isolated. The most significant activity was observed with the alkaloid extract of P8 against Staphylococcus aureus with a MIC value of 1.22 μg/mL and against Candida albicans with a MIC value of 2.4 μg/mL., Discussion: The results indicate that P. rhoeas samples (P8 and P9), which contain roemerine as their major alkaloid, were the most active extracts.

This study aimed to verify the sedative and anaesthetic effect of the essential oils of basil (Ocimum basilicum) (EOOB) and lemongrass (Cymbopogum flexuosus) (EOCF) in Nile tilapia juveniles. The fish were transferred to aquaria containing different concentrations of each essential oil: 10, 25, 50, 100, 200, 400 and 600 μL L-1. The time of sedation ranged from 7 to 31 seconds and the recommended concentration was 10 or 25 μL L-1 for both essential oils. The best times for anaesthesia and recovery were found for the concentrations of 400 μL L-1 for EOOB (135.2 and 199.1 seconds, respectively) and 600 μL L-1 for EOCF (327.1 and 374.8 seconds, respectively). In conclusion, we recommend the use of EOOB and EOCF for the sedation and anaesthesia of Nile tilapia at concentrations of 10-25 (for both), 400 and 600 μL L-1, respectively.

Bridelia micrantha is traditionally used in tropical Africa to treat a wide range of human and animal diseases. The aim of this study was to summarise the research that has been done on the ethnomedicinal uses, phytochemistry and pharmacological properties of B. micrantha so as to understand its importance and potential value in primary healthcare systems. The literature search for information on ethnomedicinal uses and pharmacological activities of B. micrantha was undertaken using databases such as Web of Science, Scopus, Google Scholar, Science Direct, BioMed Central (BMC), PubMed and Springerlink. Other relevant literature sources included books, book chapters, websites, theses, conference papers and other scientific publications. This study showed that B. micrantha is used as herbal medicine in just over half (57.3%) of the countries in tropical Africa where it is indigenous. A total of 54 ethnomedicinal uses of B. micrantha have been recorded with a high degree of consensus on burns, wounds, conjunctivitis, painful eyes, constipation, gastric ulcers, cough, headache, rheumatism, painful joints, dysentery, ethnoveterinary medicine, malaria, sexually transmitted infections, stomach ache, tape worms and diarrhoea. Different plant parts, aqueous and organic extracts exhibited anthelmintic, antimicrobial, anticonvulsant and sedative, antidiabetic, antidiarrhoeal, antinociceptive, antioxidant, antiplasmodial, antischistosomal, hepatoprotective, insecticidal and β-lactamase inhibitory activities., Competing Interests: The author declares no conflict of interest.

The sedative effects of volatile components in the essential oil of Artemisia montana ("Yomogi") were investigated and measured using gas chromatography-mass spectrometry (GC-MS). Major components identified included 1,8-cineol, camphor, borneol, α-piperitone, and caryophyllene oxide. Among them, 1,8-cineol exhibited the highest flavor dilution (FD) value in an aroma extract dilution analysis (AEDA), followed by borneol, o-cymene, β-thujone, and bornyl acetate. The sedative effects of yomogi oil aroma were evaluated by sensory testing, analysis of salivary α-amylase activity, and measurement of relative fluctuation of oxygenated hemoglobin concentration in the brain using near-infrared spectroscopy (NIRS). All results indicated the stress-reducing effects of the essential oil following nasal exposure, and according to the NIRS analysis, 1,8-cineol is likely responsible for the sedative effects of yomogi oil.

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.

Present study was conducted on crude methanolic extract of stem and root of Taverniera glabra. In Pakistan T. glabra is found in the region of Balochistan only. T. glabra has numerous therapeutic uses in traditional medicine and it is also used for the pain relief. Current study was carried out to evaluate acute toxicity, analgesic and CNS depressant activity of the plant. Acute toxicity was carried out by oral administration of the T. glabra extract from 250 to 2000mg/kg oral dose. Analgesic activity was carried out by acetic acid induced writhing test and formalin test. Central Nervous System (CNS) depressant activity was carried out by exploratory activities (open field activity, cage crossing activity, rearing test) and forced swimming test. Oral administration of the methanolic extract of T. glabra was nontoxic at the dose of 1500mg/kg in the acute toxicity test. Exploratory behavior of mice treated with the methanolic extract of T. glabra showed sedative effects (P<0.05) in open field, cage crossing, traction and rearing test, particularly at the dose of 500mg as compared with standard drug Diazepam. In forced swimming test, mobility time was significantly (P<0.05) increased at 500mg/kg oral dose, and results were significant as compared with control. Methanolic extract of T. glabra produced significant (P<0.05) analgesic effects at the dose of 500mg/kg in the acetic acid induced writhing test and the formalin test. In conclusion, results show that the crude methanolic extract of T. glabra possess sedative as well as potent analgesic effects. Present pharmacological studies are the first ever studies conducted on the methanolic extract of T. glabra.

Context Coriandrum sativum L. (Apiaceae) (coriander) is an herb grown throughout the world as a culinary, medicinal or essential crop. In traditional medicine, it is used for the relief of anxiety and insomnia. Systemic hydro-alcoholic and aqueous extract from aerial parts and seeds had anxiolytic and sedative action in rodents, but little is known about its central effect in chicks. Objective To study the effects of intracerebroventricular administration of essential oil from coriander seeds and its major component linalool on locomotor activity and emotionality of neonatal chicks. Materials and methods The chemical composition of coriander essential oil was determined by a gas-chromatographic analysis (> 80% linalool). Behavioural effects of central administration of coriander oil and linalool (both at doses of 0.86, 8.6 and 86 μg/chick) versus saline and a sedative diazepam dose (17.5 μg/chick, standard drug) in an open field test for 10 min were observed. Results Doses of 8.6 and 86 μg from coriander oil and linalool significantly decreased (p < 0.05) squares crossed number, attempted escapes, defecation number and distress calls, and significantly increased (p < 0.05) the sleeping posture on an open field compared with saline and were similar to the diazepam group. Discussion and conclusion The results indicate that intracerebroventricular injection of essential oil from Coriandrum sativum seeds induced a sedative effect at 8.6 and 86 μg doses. This effect may be due to monoterpene linalool, which also induced a similar sedative effect, and, therefore, could be considered as a potential therapeutic agent similar to diazepam.

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.

The first step for identification of medicinal plants and their therapeutic effects is to determine their use by local people, traditional medicine books and personal experiences. The aim of this study was to document the medicinal plants used as analgesic, sedative or narcotic agents by local residents of Dehloran, Iran. Interviews conducted with 53 informants (38 male and 15 female) revealed that a total of 32 medicinal plants belonging to 22 families are used in Dehloran as narcotic, sedative and analgesic agents. The most utilized plant families were Asteraceae, Rosaceae and Fabaceae. Approximately 74% of the utilized plants was attributed to herbs, followed by trees (13%) and shrubs (13%). Sixty-six percent of the medicinal plants used in the study area were perennial and the rest were annual or biannual. The most widely used plant parts were flowers (34%) followed by leaves (24%) and fruits (14%). Thirty-nine percent of the medicinal plants were used as sedatives, 39% as analgesics, and 24% as narcotics. Recommended plants in this study can be good candidates for further clinical and laboratory trials on diseases that are associated with pain, suffering, stress and depression. They also can be used to develop new sedative, narcotic and analgesic drugs.

Date-rape drugs have the potential to be used in drug-facilitated sexual assault, organ theft and property theft. Since they are colorless, tasteless and odorless, victims can drink without noticing, when added to the beverages. These drugs must be detected in time, before they are cleared up from the biofluids. A simultaneous extraction and determination method in urine for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin (an anticonvulsant and antiepileptic drug) with LC-MS/MS was developed for the first time with analytically acceptable recoveries and validated. A 4 steps liquid-liquid extraction was applied, using only 1.000mL urine. A new age commercial C18 poroshell column with high column efficiency was used for LC-MS/MS analysis with a fast isocratic elution as 5.5min. A new MS transition were introduced for barbital. 222.7>179.8 with the effect of acetonitrile. Recoveries (%) were between 80.98-99.27 for all analytes, except for GHB which was 71.46. LOD and LOQ values were found in the ranges of 0.59-49.50 and 9.20-80.80ngmL(-1) for all the analytes (except for GHB:3.44 and 6.00μgmL(-1)). HorRat values calculated (between 0.25-1.21), revealed that the inter-day and interanalist precisions (RSD%≤14.54%) acceptable. The simultaneous extraction and determination of these 8 analytes in urine is challenging because of the difficulty arising from the different chemical properties of some. Since the procedure can extract drugs from a wide range of polarity and pKa, it increases the window of detection. Group representatives from barbiturates, z-drugs, ketamine, phenytoin and polar acidic drugs (GHB) have been successfully analyzed in this study with low detection limits. The method is important from the point of determining the combined or single use of these drugs in crimes and finding out the reasons of deaths related to these drugs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Terminalia ivorensis A. Chev (Combretaceae) is a medicinal plant used in folk medicine in the management of pain, rheumatic condition, gastroenteritis and as a tranquilizer in psychotic disorder., Objective: We evaluated neurobehavioural and analgesic properties of the ethanol bark extract of T. ivorensis (EBETI)., Materials and Methods: Effects of EBETI (1.25, 2.5, and 5 mg/kg) on novelty-induced behaviours were determined using open field test. Anxiolytic effect of EBETI (1.25, 2.5, and 5 mg/kg) was assessed using hole-board and elevated-plus maze paradigms. Analgesic property of EBETI (2.5, 5, and 10 mg/kg) was evaluated using acetic acid induced writhing, formalin and tail immersion tests. The extract was administered once intraperitoneally., Results: The LD50 of EBETI was 173 mg/kg. EBETI (1.25, 2.5, and 5 mg/kg) significantly reduced rearing (142.3±1.6, 83.5±1.9, 39.3±1.5) and grooming (33.8±3.4, 28.4±3.0, 18.2±1.7) as compared with controls (180.5±4.9; 52.4±5.2). Treatment with EBETI (1.25, 2.5, and 5 mg/kg) significantly reduced head-dipping on hole-board (9.4±2.3, 6.2±1.9, 5.4±2.9) as compared with control (26.8±1.9). However, there was no anxiolytic effect on EPM. EBETI (2.5, 5, and 10 mg/kg) significantly inhibited abdominal constriction in writhing assay (21.8.0±2.4, 12.2±1.6, 5.8±2.1) as compared with control (35.0±1.7). Inhibition of neurogenic and inflammatory phases of formalin test was notice. However, the extract could not alter response to thermal stimulus in tail immersion test., Discussion and Conclusion: EBETI is sedative and has analgesic effect, thus supporting its folkloric use in pain management and as a tranquilizer in psychosis., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.)

Spikenard, the dried roots of Nardostachys chinensis, contains sesquiterpenoids and is widely used as an herbal tranquilizer. We previously demonstrated that spikenard vapor showed a sedative effect when administered by inhalation, and we identified hydrocarbon sesquiterpenoids as active components. Here we investigated the other components that contribute to the effects of spikenard. Six oxygenated sesquiterpenoids, including aristolane- and guaiane-types, were isolated from an acetone extract of spikenard. We evaluated the sedative activities of these oxygenated compounds using an inhalation administration method in a caffeine-treated excitatory mouse model. We identified aristolen-1(10)-en-9-ol and patchouli alcohol as highly effective sedative components. These compounds inhibited locomotion in mice by approximately 60% at a dose of 300 µg/cage. In addition, aristolen-1(10)-en-9-ol prolonged pentobarbital-induced sleep to the same extent as 1 mg/kg diazepam. This effect completely disappeared with the administration of the GABAA-benzodiazepine receptor antagonist flumazenil (3 mg/kg), suggesting that the sedative effect of aristolen-1(10)-en-9-ol is expressed via the GABAergic system. Furthermore, differently from diazepam, inhalation of aristolen-1(10)-en-9-ol for 1 h did not affect the motor coordination in the rota-rod test. In the present study, we identified active components and provided evidence supporting the traditional sedative use of spikenard. Our research suggests that aristolen-1(10)-en-9-ol may be an effective aromatherapy, providing mild sedation., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Characterization of sedative, possible anticonvulsant, and protective effects of Acacetin-7-O-glucoside (7-ACAG)., Methods: 7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. Brains of each group of rats were prepared for histological analysis., Results: Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro, similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus., Conclusions: 7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound's being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries.

A novel method using ultra-high performance liquid chromatography coupled to hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap) was developed and validated for the simultaneous screening, identification and quantification of sedative-hypnotics in dietary supplements. Chromatographic conditions were optimised and a full data-dependent MS(2) scan (MS/dd-MS(2)) in positive and negative ion mode was used. A single injection was sufficient to perform the simultaneous screening and identification/quantification of samples. The response showed a good linear relationship with analyte concentrations over wide ranges (e.g., 1.0-1000 ng g(-1) for diazepam) with all the determination coefficients (r(2)) > 0.9985. The method was validated, obtaining accuracy (intra- and inter-day) in the range of 94.5-105.3% and precision (intra- and inter-day) in the range of 0.4-8.9%, respectively. The detection limits (LODs) were in the range of 0.3-1.0 ng g(-1) for different analytes. Recoveries were performed and ranged from 74.1% to 90.2%, while all matrix effects were over the range of 85.4-93.6%. Finally, this method was used to detect sedative-hypnotics in commercial dietary supplements. Of a total of 45 batches of dietary supplements, only three batches were found to be positive samples with concentrations of diazepam, clonazepam and alprazolam at high levels (≥ 8.22 mg g(-1)).

This paper describes a method for the determination of eight sedative hypnotics (benzodiazepines and barbiturates) in sewage sludge using pressurized liquid extraction and liquid chromatography with tandem mass spectrometry. Pressurized liquid extraction operating conditions were optimized and maximum recoveries were reached using methanol under the following operational conditions: 100ºC, 1500 psi, extraction time of 5 min, one extraction cycle, flush volume of 60% and purge time of 120 s. Pressurized liquid extraction recoveries were higher than 88% for all the compounds except for carbamazepine (55%). The repeatability and reproducibility between days, expressed as relative standard deviation (n = 5), were lower than 6 and 10%, respectively. The detection limits for all compounds were lower than 12.5 μg/kg of dry weight. The method was applied to determine benzodiazepines and barbiturates in sewage sludge from urban sewage treatment plants, and carbamazepine showed the highest concentration (7.9-18.9 μg/kg dry weight)., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The present study describes the isolation of linalool from the essential oil of Lippia alba (Mill.) N. E. Brown, and its anesthetic effect in silver catfish (Rhamdia quelen) in comparison with essential oil. The potentiation of depressant effects of linalool with a benzodiazepine (BDZ) and the involvement of GABAergic system in its antagonism by flumazenil were also evaluated., Study Design: Prospective experimental study., Animals: Juvenile silver catfish unknown sex weighing mean 9.24 ± 2.83 g (n = 6 for each experimental group per experiment)., Methods: Column chromatography was used for the isolation of S-(+)-linalool. Fish (n = 6 for each concentration) were transferred to aquaria with linalool (30, 60, and 180 μL L(-1)) or EO of L. alba (50, 100, and 300 μL L(-1)) to determine the induction time for anesthesia. After induction, the animals were transferred to anesthetic-free aquaria to assess their recovery time. To observe the potentiation, fish were exposed to linalool (30, 60, and 180 μL L(-1)) in the presence or absence of BDZ (diazepam 150 μm). In another experiment, fish exposed to linalool (30 and 180 μL L(-1) or BDZ were transferred to an anesthetic-free aquaria containing flumazenil (5 μm) or water to assess recovery time., Results: Linalool had a similar sedation profile to the essential oil at a proportional concentration in silver catfish. However, the anesthesia profile was different. Potentiation of linalool effect occurred only when tested at low concentration. Fish exposed to BDZ showed faster anesthesia recovery in water with flumazenil, but the same did not occur with linalool., Conclusions and Clinical Relevance: The use of linalool as a sedative and anesthetic for silver catfish was effective at 30 and 180 μL L(-1), respectively. The mechanism of action seems not to involve the benzodiazepine site of the GABAergic system., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

The methanol-soluble extract from the root of Ipomoea tyrianthina was studied in order to isolate compounds with activity on the central nervous system and vasorelaxant effects. Chromatographic methods were used to isolate and purify seven new glycolipids (2-8). The structures of compounds 1-8 were elucidated by a combination of NMR spectroscopy and mass spectrometry. Tyrianthinoic acid (1) is a glycosidic acid composed of a linear pentasaccharide core bonded to a 11-hydroxyhexadecanoic acid. The structure of tyrianthinic acids III (2), IV (3), and V (4) consists of a partially acylated tyrianthinoic acid. Tyrianthinic acid VI (8) is a tetrasaccharide core bonded to a jalapinolic acid, acylated by a 2-methyl-3-hydroxybutanoic acid. Tyrianthins C (5), D (6), and E (7) are ester-type heterodimers of scammonic acid A with different acylating residues in the two monomeric units. The macrolactonization site was located at C-3 of the rhamnose unit. The position of the ester linkage for monomeric unit B on the macrocyclic unit A was established at C-4 of the terminal quinovose. Compounds 5-7 increased the sleeping time induced by pentobarbital and the release of gamma-aminobutyric acid in brain cortex. In addition, compounds 5-7 showed significant in vitro relaxant effects on aortic rat rings, in endothelium- and concentration-dependent manners.

The fruits of Schisandra chinensis have been used for the treatment of insomnia in oriental countries for more than thousands of years. However, the pharmacological properties and the mechanism of sedative and hypnotic effects have not yet been studied. Gomisin N is one of the major bioactive constituents from the fruits of Schisandra chinensis, and in this paper we reported a detailed study on the effects and mechanisms of Gomisin N on its sedative and hypnotic activity for the first time. These results implied that Gomisin N possessed weak sedative effects on locomotion activity in normal mice, and produced a dose-dependent(5-45 mg/kg, i.p.) increase in sleep duration in pentobarbital-treated mice, thus, itself did not induce sleep at higher dose which was used in this experiment (45 mg/kg, i.p.). It also can reverse the rodent models of insomnia induced by p-chlorophenylalanine (PCPA) and caffeine, which could exhibit a synergistic effect with 5-hydroxytryptophan (5-HTP) as well; furthermore, the hypnotic effects of Gomisin N were inhibited by flumazenil (a specific GABAA-BZD receptor antagonist). Altogether, these results indicated that Gomisin N produced beneficial sedative and hypnotic bioactivity, which might be mediated by the modification of the serotonergic and GABAergic system., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Valerian root and lemon balm extracts have previously shown efficacy and excellent tolerability in children<12 years suffering from restlessness and insomnia. We now examined whether treatment with a fixed combination of both may also improve concentration, hyperactivity and impulsiveness., Methods: 169 primary school children suffering from hyperactivity and concentration difficulties but not meeting ADHS criteria were treated in an observational study by 27 office based pediatricians with a recommended daily dose of 640 mg valerian root extract WS(®) 1014 and 320 mg lemon balm extract WS(®) 1303 (Sandrin(®)), and evaluated by pediatricians and parents using standardized questionnaires at baseline, weeks 2 and 7., Results: The fraction of children having strong/very strong symptoms of poor ability to focus decreased from 75% to 14%, hyperactivity from 61% to 13%, and impulsiveness from 59% to 22%. Parent rated social behavior, sleep and symptom burden showed highly significant improvements. Only in two children mild transient adverse drug reactions were observed., Conclusion: In primary school children with restlessness, concentration difficulties and impulsiveness treatment with WS(®) 1014 and WS(®) 1303 (Sandrin(®)) provides a viable option in addition to counseling and education., (Copyright © 2014. Published by Elsevier GmbH.)

A new caryophyllane derivative, caryophyllenol A, and a new germacrane derivative, isovolvalerenal D, together with 11 known sesquiterpenoids, were isolated from a petroleum ether partition of the roots and rhizomes of Valeriana amurensis. Structure elucidation of caryophyllenol A and isovolvalerenal D was accomplished on the basis of various spectroscopic techniques including HRESIMS and 2D NMR analyses. The structure of caryophyllenol A was further confirmed by X-ray crystallography and using quantum-chemical ECD calculation adopting TDDFT method. Caryophyllenol A and other eight sesquiterpenoids were evaluated for sedative activity with the model of Drosophila melanogaster, and eight of them showed the effect of prolonging the total sleeping time (TST) of D. melanogaster, displaying significant sedative action., (Copyright © 2014 Elsevier B.V. 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.)

Bangladesh is a good repository of medicinal plants. Traditional healers utilize them for treating many pathological states. Unfortunately, very few of them have been scientifically evaluated to know about the deep inside. The current study here is designed to evaluate the in vivo sedative activity of the leaves of Glochidion multiloculare (Rottler ex Willd) Voigt. With this purpose, the plant leaves were collected and powdered for extraction with methanol. Initially, the plant extract was subjected to brine shrimp lethality bioassay to monitor the presence of bioactive molecules. Later on, different neuropharmacological studies including hole cross, open field, thiopental-sodium induced sleeping time and Elevated-Plus Maze (EPM) tests were conducted to investigate sedative action. In the brine shrimp lethality bioassay, the LC50 value of the extract was found 37.19 μg mL(-1), whereas the standard vincristine sulphate showed the LC50 10.50 μg mL(-1). The moderate toxicity of the extract on brine shrimp indicated the existence of bioactive secondary metabolites in this extract. Besides, the extract decreased the locomotor activity of mice in hole cross, open field and EPM test indicating the CNS depression capability of the plant. Moreover, the extract was very much effective for prolonging the sleeping time (103 min) with quick onset of action (22 min) in comparison to the control group. The efficacy of the plant extract was found closer to the common sedative drug diazepam. Further investigations are required to explore the underlying mechanism of the sedative action and isolate bioactive principles.