Epidemiological Characteristics of Sedative-Hypnotics and Opioid Painkillers at High-Frequency Exposure / 法医学杂志

Drug poisoning has a high incidence and serious consequences in medical institutions; its epidemiological characteristics also directly affect the changes in national laws and policies and the implementation of local management policies. Chinese statistics on drug-related abnormal death cases generally come from judicial appraisal centers and medical units. However, due to differences in work content and professional restrictions, there are differences in information management forms, which makes it difficult for appraisers to conduct a professional and systematic analysis of drug-related cases. This article focuses on the analysis of epidemiological characteristics of sedative-hypnotics and opioid painkillers and their exposure patterns in cases of poisoning death by analyzing the annual report of the American Association of Poison Control Center, combined with the characteristics of drug exposure in China.

Regulation of Hypnotic Active Components of Cnidii Fructus on Melatonin Synthesis Rate-limiting Enzyme AANAT in Rats with PCPA-induced Insomnia / 中国实验方剂学杂志

Objective:To observe the effects of Cnidii Fructus hypnotic active components （CHC） on the behaviors of rats with p-chlorophenylalanine （PCPA）-induced insomnia and melatonin （MT） synthesis rate-limiting enzyme arylalkylamine <italic>N</italic>-acetyltransferase （AANAT）， and explore the protective mechanism of CHC on the pineal gland. Method:Male SD rats of SPF grade were randomly divided into a blank control group， a model group， a MT group， and high-， medium-， and low-dose CHC groups with 10 rats in each group. Except for the blank control group， other groups received 4.5% PCPA suspension at 10 mL·kg^-1， intragastric administration， for two consecutive days. After PCPA model of insomnia was established， normal and model groups were gavaged at the same volume of 2% Tween-80， MT control group （10 mg·kg^-1）， CHC was high， medium and low （60， 30， 15 mg·kg^-1）， 10 mL·kg^-1， once a day， for consecutive 7 days. Four days after administration， open field， elevated cross maze， and pentobarbital sodium-induced sleep tests were conducted， respectively. Serum MT was detected by enzyme-linked immunosorbent assay. The mRNA expression level of AANAT was determined by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The expression of AANAT protein in the pineal gland was detected by Western blot. Result:Compared with the results in the blank control group， the total distance of open field activity and standing times and duration in the central area were increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， the proportions of open arm entry （OE%） and open arm time （OT%） were decreased （<italic>P</italic><0.05）， and the sleep latency was prolonged （<italic>P</italic><0.01） in the model group. Compared with the model group， no significant difference was observed in the low-dose CHC group， while other groups exhibited reduced total distance of activity （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated OE% （<italic>P</italic><0.05）， shortened sleep latency， and prolonged sleep time （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the serum MT in the blank control group， that in the model group was decreased （<italic>P</italic><0.01）. Compared with the model group， no significant difference was observed in the low-dose CHC group， while other groups displayed increased serum MT （<italic>P</italic><0.05）. The mRNA and protein expression of AANAT was decreased in the model group as compared with that in the blank control group （<italic>P</italic><0.01）. Compared with the model group， the MT group and the high-dose CHC group showed up-regulated expression （<italic>P</italic><0.05）. Conclusion:CHC improved the behavioral indexes of PCPA-induced insomnia， increased the synthesis and secretion of MT in pineal cells， and elevated the serum MT level， which was related to the up-regulation of the mRNA and protein expression of AANAT in the pineal gland.

Appraising the Neurobehavioural Toxicity Potential of Aqueous Methanol Leaf Extract of Tapinanthus globiferus Growing on Azadirachta indica

The high prevalence and disease burden of anxiety disorders against the paucity and liabilities of existing anxiolytics indicates a need for the discovery of additional/new anti-anxiety agents. However, it is necessary to further screen these new/putative anxiolytic compounds/extracts to rule out the unwanted neurobehavioural toxicities inherent in the existing anti-anxiety drugs. Aqueous methanol leaf extract of Tapinanthus globiferusgrowing on Azadirachta indicahost tree has previouslydemonstrated significant (p<0.05) anxiolytic effects in mice. This study, therefore, set out to counter-screen this extract for locomotion-suppressant, acute amnesic, sedative (myorelaxant) and hypnotic effects using standard mouse behavioural and biochemical paradigms. The leaf extract (150, 500 and 1500 mg/kg) did not cause significant (p>0.05) alterations in spontaneous locomotor activity, motor coordination/balance, sleep onset or duration,but dose-dependent and significant (p<0.05) increases (63.28±5.63, 65.63±4.12 and 69.18±3.69) in novel object recognition indices of extract-treated compared to 51.54±4.03 and 61.06±2.91 scores in diazepam-and aqua-treated mice, respectively.These findings indicate the aqueous methanol leaf extract is mostly devoid of the evaluated neurobehavioural toxicities and may possess short-term memory enhancement property in mice. These findings may justifythe traditional use of Tapinanthus globiferusextracts for memory enhancement

Sedative and Hypnotic Effects and Transcriptome Analysis of Polygala tenuifolia in Aged Insomnia Rats / 中国结合医学杂志

OBJECTIVE@#To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia (PT) on treating aged insomnia rats.@*METHODS@#Sixty Sprague-Dawley male rats were divided into 6 groups by a random number table, including control group, model group, diazepam group (0.92 mg/kg), as well as PT low-, medium- and high-dose groups (0.0875, 0.175, 0.35 g/kg, respectively), 10 rats in each group. Aged insomnia rat model was established with subcutaneous injection of D-galactose for 42 days and then intraperitoneal injection of para-chlorophenylalanine for 3 days. PT and diazepam were respectively given to aged insomnia rats by intragastric administration for 7 days after model establishment. Then the rats were investigated by body weight, Morris water maze test, pentobarbital test, enzyme-linked immunosorbent assay, and transcriptome sequencing.@*RESULTS@#Compared with the model group, PT increased the body weight, improved memory ability, and prolonged pentobarbital-induced sleep time of aged insomnia rats (P<0.01 or P<0.05). The medium dose of PT also increased the neurotransmitter levels of 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA), and decreased the level of Glu in the hippocampus of aged insomnia rats (P<0.05 or P<0.01). Twenty-four differentially expressed genes (DEGs) were overlapped among model group, medium-dose PT group, and diazepam group in transcriptome analysis. Fuom and Pcp2 were down-regulated by the treatment of medium-dose PT (P<0.01 or P<0.05). The metabolic pathways of PT were relatively less than diazepam (91 vs. 104).@*CONCLUSIONS@#The sedative and hypnotic effects of PT in aged insomnia rats might be related to neuro, metabolism pathways, especially through GABAergic signaling pathway. It provided more effective herb choice for the treatment of senile insomnia.

Safety on Chloral Hydrate Oral Solution for Sedative and Hypnotic in Children ：A Systematic Review / 中国药房

OBJECTIVE：To systematically evaluate the safety of Chloral hydr ate（CH）oral solution for sedative and hypnotic in children，and to provide evidence-based reference for clinical use. METHODS ：Retrieved from 9 electronic databases （PubMed， Cochrane Library ，Embase，CINAHL，International Pharmaceuticals ，CNKI，CBM，Wanfang Database ，VIP），3 clinical trial registry platforms （Clinical Trials ，Cochrane Clinical Trial Database ，WHO Clinical Trial Database ）and 18 adverse drug reaction （ADR）monitoring systems （ADR monitoring websites of WHO ，USA，Switzerland，China and other countries/areas/international organizations），during the date of database establishment to March 2019，the reports of randomized controlled trials ，cohort studies，case-control studies ，case series studies ，case reports ， cross-sectional studies and adverse reactions monitoring network of chloral hydrate versus other interventions （blank 85503205。E-mail：chenzhehx@163.com control，placebo or other sedative hypnotics ）for children ’s sedative and hypnotic safety were collected. After data extraction of included literatures met inclusion criteria ，quality mail：zhanglingli@scu.edu.cn evaluation of included s tudies with Cochrane bias risk evaluation manual （RCT），Newcastle-Ottawa scale evaluation tool （Cohort study and case control study ），Australian JBI quality assessment tool （case series study and case report study ），Meta-analysis was performed by Rev Man 5.3 software，or descriptive analysis was conducted. RESULTS ：A total of 54 studies were included ，among which there were 13 RCTs，9 cohort studies ，17 case series studies ，13 case reports ，and 2 reports from ADR monitoring network. Based on the results of RCT and cohort studies ， the incidence of Chloral hydrate oral solution adverse events was 7.25％. There was no statistical significance in the incidence of digestive system [RR ＝0.87，95％ CI（0.14，5.42），P＝0.88]，nervous system [RR ＝0.13，95％ CI（0.01，2.41），P＝0.17]， cardiovascular system [RR ＝2.12，95％ CI（0.08，56.57），P＝0.65] adverse event between Chloral hydrate oral solution and midazolam. The incidence of respiratory system adverse events induced by Chloral hydrate oral solution was higher than that of midazolam [RR ＝3.07，95％CI（1.94，4.86），P＜0.01]. There was no statistical significance in the incidence of digestive system adverse events between Chloral hydrate oral solution and diazepam [RR ＝0.71，95％CI（0.47，1.10），P＝0.13]. There was no statistical significance in the incidence of digestive system ，nervous system and cardiovascular system adverse events between Chloral hydrate oral solution and barbiturates （P＞0.05）. CONCLUSIONS ：Chloral hydrate oral solution is similar to midazolam ， diazepam and barbiturates in terms of digestive ，nervous and cardiovascular systems adverse events ，but the incidence of respiratory system adverse events is higher than midazolam.

Hipnosis anestésica inducida por profesional de Enfermería. Reporte de un caso / Nursing staff induced anesthetic hypnosis: A case report / Hipnose anestésica induzida por profissional de Enfermagem. Relatório de um caso

Resumen Introducción: La hipnosis anestésica puede ser un recurso útil para procedimientos dolorosos. Desarrollo: Se reporta caso de una joven que requiere exodoncia de terceros molares, con uso de hipnosis como único anestésico. El proceso de enfermería inicia con la valoración según patrones funcionales, impresiona lo sana que se encuentra, sin antecedentes mórbidos relevantes ni contraindicación para anestesia química. Se selecciona diagnóstico NANDA de Disposición para mejorar el confort. Dentro del plan se incorporan el NIC 5920 Hipnosis y 5922 Facilitar la autohipnosis, con buena evolución según lo planificado. Resultados: La extracción con hipnosis anestésica se desarrolló de forma similar a la cirugía con anestesia química, la cual se realizó sin dolor. En posoperatorio, paciente practica autohipnosis, sin necesitar analgésicos y evolucionó favorablemente. Discusión: La hipnosis requiere mayor evidencia científica, pero su uso es prometedor. Se constataron los beneficios de la hipnosis en el abordaje del dolor. Conclusión: La hipnosis anestésica, fue útil como intervención de enfermería en cirugía dental. La autohipnosis contribuyó al buen resultado. El profesional de Enfermería entrenado en hipnosis está en condiciones de incorporarla en la gestión del cuidado. El caso resulta interesante, dado que la paciente opta por la hipnosis, sin contraindicación para anestesia química, ya que no se encontró otro reporte de hipnoanestesia inducida por profesional de Enfermería, como anestésico único. Anecdóticamente, durante la filmación del procedimiento, una periodista entra espontáneamente en trance, por lo que requiere intervención del profesional de Enfermería para salir de él.

Abstract Introduction: Anesthetic hypnosis can be a useful resource to address painful procedures. Development: The case is of a young female patient requiring third-molars exodontia who underwent it under anesthetic hypnosis. The nursing process began with the assessment according to functional patterns. The patient was found healthy and without relevant morbid antecedents nor drug-anesthesia contraindications. A comfort improving disposition NANDA diagnosis was selected. NIC 5922 and 5920 were incorporated to the intervention plan. Results: The extraction under anesthetic hypnosis was performed in a similar form in comparison to a drug-anesthesia extraction procedure. During the post operatory stage, the patient used self-hypnosis and responded favorably without analgesics. Discussion: While hypnosis requires more scientific evidence, its use appears to be promising. In this case, diverse benefits from using hypnosis to address a painful procedure were acknowledged. Conclusion: Anesthetic hypnosis proved being helpful in a dental-surgery related nursing intervention. Self-hypnosis also contributed to the favorable outcome. A nursing professional who is well trained in hypnosis can incorporate this kind of procedure into her care management approach. This particular case was interesting because the patient chose hypnosis over drug anesthesia, and no other report on a nursing staff induced anesthetic hypnosis was found. Anecdotally, during the filming of this procedure, a journalist suffered an emotional trance which required immediate nursing intervention.

Resumo Introdução: A hipnose anestésica pode ser um recurso útil para procedimentos dolorosos. Desenvolvimento: Informa-se o caso de uma garota que requer exodontia de terceiros molares, com uso de hipnoses como único anestésico. O processo de enfermagem inicia com a valoração segundo padrões funcionais, impressiona o saudável que se encontra, sem antecedentes mórbidos relevantes nem contraindicação para anestesia química. Seleciona-se diagnóstico NANDA de Disposição para melhorar o conforto. Dentro do plano se incorporam o NIC 5920 Hipnose e 5922 Facilitar a auto-hipnose, com boa evolução segundo o planejado. Resultados: A extração com hipnose anestésica desenvolveu-se de forma similar à cirurgia com anestesia química, a qual se realizou sem dor. Em pós-operatório, o paciente prática auto-hipnose, sem precisar analgésicos e evolucionou favoravelmente. Discussão: A hipnose requer maior evidencia científica, mas seu uso é promissor. Verificaram os benefícios da hipnose na abordagem da dor. Conclusão: A hipnose anestésica foi útil como intervenção de enfermagem em cirurgia dental. A auto-hipnose contribuiu para o bom resultado. O profissional de Enfermagem treinado em hipnose está em condições de incorporá-la na gestão do cuidado. O caso resulta interessante, dado que a paciente opta pela hipnose, sem contraindicação para anestesia química, já que não se encontrou outro relatório de hipnoanestesia induzida por profissional de Enfermagem, como anestésico único. Anedoticamente, durante a filmagem do procedimento, uma jornalista entrou espontaneamente em transe, pelo qual se requereu intervenção do profissional de Enfermagem para sair dele.

Determination of five neurotransmitters in the rat brain for the study of the hypnotic effects of Ziziphi Spinosae Semen aqueous extract on insomnia rat model by UPLC-MS/MS / 中国天然药物

Ziziphi Spinosae Semen (ZSS) has been used for treatment of insomnia in China for centuries. To reveal the influence of insomnia on the levels of the neurotransmitters including serotonin (5-HT), glutamic acid (Glu), γ-aminobutyric acid (GABA), noradrenaline (NE) and dopamine (DA), and to study the role of ZSS aqueous extract in the treatment of insomnia, an UPLC-ESI- MS/MS method was developed and validated for simultaneous determination of five neurotransmitters in the rat brain. The brain samples were pretreated by one-step direct protein precipitation with acetonitrile. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 10 min. The method showed a good linearity (R > 0.9967) with the other validation parameters were within acceptance range. The results indicated that the concentration of 5-HT, GABA and DA is significantly lower (P < 0.01) in para-chlorophenylalanine (PCPA)-induced insomnia rat model group, while Glu and NE significantly higher than those in control group (P < 0.01). Treatment with ZSS aqueous extract (4 or 8 g·kg·d for seven days) could ameliorate the symptoms of insomnia by significantly changing the levels of the neurotransmitter parameters mentioned above. The data obtained in this study demonstrate that ZSS aqueous extract could ameliorate the symptoms of insomnia by modulating the levels of monoamines and amino acid neurotransmitters in the brain.

Enrichment of flavonoid aglycones in licorice extract enhanced anti-inflammatory potential,but its hypnotic effect was not altered / 中国药理学与毒理学杂志

OBJECTIVE Licorice is used throughout the world as a traditional herbal remedy. Ac-cording to Chinese traditional medicine licorice alone can be used to treat inflammation.Although there have been some studies investigated the anti-inflammatory ingredients of licorice, but for the potency of flavonoid glycoside and their aglycones on inflammation are not evaluated.This study was designed to assess the contributions of licorice flavonoid glycosides and their aglycons to its anti-inflammatory and hypnotic effects. METHODS For the flavonoid aglycone's enrichment, the extract of licorice (EL) was fermented in submerged culture of the edible fungus Grifola frondosa HB0071 mycelia which can produce β-glucosidase and catalyze the flavonoid glycosides to aglycones.EL and fermented extract of licorice (FEL) were used in this study. The anti-inflammation test was carried out in arachidonic acid (AA)-induced ear edema model and the hypnotic test was performed by using electroencephalogram (EEG)analysis method in normal freely moving SD rats.The chemicals constituents were analyzed by HPLC.RESULTS During fermentation,the falvonoid glycosides of licorice were hydrolyzed by the time process.Along with fermentation time,the concentration of the major flavonoid glycosides,liquiritin and isoliquiritin were decreased obviously, and simultaneously their aglycons, liquiritigenin and isoliquiriti-genin were remarkably increased in FEL.Moreover,the content of another major constituent glycyrrhi-zic acid and glycyrrhetinic acid were not changed after the fermentation. In AA-induced mice ear ede-ma test,after topical application,FEL(effective dose range:5-20 μg·ear-1)showed more potent inhibito-ry activity than EL(effective dose range:25-100 μg·ear-1).On the other hand,oral administration of EL and FEL exhibited the same hypnotic potency and both enhanced the total sleep time including rapid eye movement (REM) sleep and non-REM sleep time. CONCLUSION These results suggested that the enrichment of flavonoid aglycons such as liquiritigenin and isoliquiritigenin enhanced the anti-inflam-matory potency of licorice extract,and this potentiation has nothing to do with glycyrrhizic acid or glycyr-rhetinic acid.In addition,enrichment of flavonoid aglycones did not alter the hypnotic effect of licorice.

Evaluation of antipyretic, sedative and hypnotic activities of methanol extract of Tabebuia hypoleuca (C. Wright ex Sauvalle) Urb. stems / [Evaluación de la actividad antipirética, sedante e hipnótica del extracto metanólico de los tallos de Tabebuia hypoleuca (C. Wright ex Sauvalle) Urb

Species of the genus Tabebuia are used in traditional medicine and are reported in the literature for their properties against various diseases. The objective of this study was to evaluate the antipyretic, sedative and hypnotic activities of methanol extract of Tabebuia hypoleuca stems (THME) using the Brewer's yeast induced pyrexia, Open field and Sodium thiopental-induced sleeping time tests, respectively. In the Brewer's yeast induced pyrexia test, THME at 500 mg/kg produced a significant (p<0.001) decrease of the fever as from the first hour after administration and was sustained for 4 h. In the Open-field test, THME did not cause any significant change in the number of crossings, rearing, preening and defecation, and either in the time of immobility. Moreover, THME did not produce changes in neither the sleeping latency nor the sleeping time induced by sodium thiopental. These results showed that THME administered orally at 500 mg/kg exerts antipyretic activity, probably mediated by the inhibition of the enzyme cyclooxygenase-2. This study also showed that THME does not exert sedative and hypnotic effects at the doses tested.

Especies del género Tabebuia se utilizan en la medicina tradicional y se reportan en la literatura por sus propiedades contra diversas enfermedades. El objetivo de este estudio fue evaluar la actividad antipirética, sedante e hipnótica del extracto metanólico de los tallos de Tabebuia hypoleuca (THME) utilizando las pruebas de pirexia inducida por levadura de cerveza, campo abierto y tiempo de sueño inducido por tiopental sódico respectivamente. En el ensayo de pirexia inducida por levadura de cerveza, THME a 500 mg/kg produjo una reducción significativa (p<0.001) de la fiebre a partir de la primera hora después de la administración y se mantuvo durante cuatro horas. En el ensayo de campo abierto, THME no causó ningún cambio significativo en el número de cruces, levantamientos, acicalamientos y defecación, ni en el tiempo de inmovilidad. Además, THME no produjo cambios ni en la latencia de sueño, ni en el tiempo de sueño inducido por tiopental sódico. Estos resultados mostraron que THME administrado oralmente en dosis de 500 mg/kg posee actividad antipirética, mediado probablemente a la inhibición de la enzima ciclooxigenasa-2. Este estudio también demostró que THME no posee actividad sedante e hipnótica en las dosis ensayadas.

Synthesis of mucunaguanide / 中国药科大学学报

The aim of this study was to synthesize 1-(5-(hydroxymethyl)-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-yl) guanidine (mucunaguanide),a pyrazinone alkaloid compound extracted from the seed of Stizotobium cochinchinensis.Starting from benzyloxy acetaldehyde,following four steps in reaction including condensation,cyclization,substitution and hydrogenation reaction,mucunaguanide was synthesized with total yield of 27.9％,and purity of more than 97.5％.Structures of all the intermediates and target compound were confirmed by IR,1H NMR and MS.This synthetic process was characterized with raw materials available,simple in operation with much milder reaction conditions,and was an ideal method of synthesis of this compound.

Pharmacodynamic study on Tianma Lingzhi Granules / 中草药

Objective: To study the pharmacodynamics of Tianma Lingzhi Granules (TLG). Methods: Mouth breathing experiment and hypoxia tolerance experiment under atmospheric pressure with mice, experiment of dizziness of guinea pigs caused by chloroform, and stimulus ischemic vertigo of model rats caused by rotating in water maze experiment was used to investigate the anti-vertigo effect of TLG; The experiment of autonomic activities of mice and hypnosis experiment of mice with pentobarbital sodium was used to investigate the sedative hypnotic effect of TLG; The experiments of torsion body and hot plate of mice was used to investigate the analgesic effect of TLG; The experiments of swimming and regulating immune experiment was used to investigate the anti-fatigue and immune regulation effect of TLG. Results: TLG could promote the supplying of oxygen in the brain, significantly reduce the times of autonomic activities of mice, increase the number of sleeping mice at the subthreshold dose of sodium pentobarbital, shorten the sleep latency of mice with hreshold dose of sodium pentobarbital and prolong the sleep time, significantly increase mice body torsion reaction latency by the acetic acid and reduce the body torsion times, and increase the spleen thymus index, clearance coefficient and phagocytic index of mice. Conclusion: TLG has the effect of treating dizziness, forgetfulness, waist and knee fatigue weakness and so on.

Iconicidade e Complexidade na Comunicação Hipnótica / Iconicity and Complexity in Hypnotic Communication

RESUMO O presente trabalho busca promover uma aproximação teórica entre a inconicidade, capacidade dos signos de transmitirem qualidades de um objeto, e uma perspectiva complexa da comunicação hipnótica. Essa discussão é desenvolvida em torno de três tópicos principais. O primeiro é a heterogeneidade semiótica dos processos comunicacionais da hipnose; o segundo consiste numa articulação entre o individual e o coletivo; e o terceiro, nas relações entre a noção de ethos e sentimento. O trabalho é concluído destacando que, malgrado as dificuldades conceituais, as relações entre iconicidade e complexidade proporcionam grandes contribuições no que diz respeito a temas importantes da comunicação hipnótica, como a subjetividade, a experiência do terapeuta, a pesquisa e o pertencimento.

ABSTRACT The present paper proposes a theoretical approximation between iconicity, which is the signs’ ability to transmit the resemblance with objects, and a complex perspective of hypnotic communication. The discussion is developed based on three main topics. The first is that of semiotic heterogeneity of communicative processes of hypnosis; the second consists of an articulation between the individual and the collective; and third, in the relation between the notions of ethos and sentiment. The paper concludes that in spite of conceptual difficulties the relationship between iconicity and complexity propitiate great contributions regarding important themes in hypnotic communication, such as subjectivity, the therapist’s experience, research, and belonging.

Research progress on Polygalae Radix / 中草药

Polygalae Radix used as Chinese materia medica has a long history. The main chemical constituents include triterpenoid saponins, xanthones, oligosaccharide esters, and so on. The study shows that Polygalae Radix has a wide range of pharmacological activities, such as sedative hypnotic, anticonvulsant, antiaging, antidementia, brain protection, cough expectorant, antidepressant, antibacterial, and anticancer. In this paper, through referring to the domestic and foreign relevant literatures on Polygalae Radix systematically, we summarize the chemical composition, pharmacological activity, and structure activity relationship of Polygalae Radix, which could provide the reference for the further investigation and development of this plant.

Nuclear magnetic resonance-based metabonomics for sedative and hypnotic effect of Banxia Houpo decoction / 中国中药杂志

Insomnia was a common disease, which might be correlated with γ-aminobutyric acid A (GABAA) receptor mechanism, cytokine regulatory mechanism, excitatory amino acid mechanism and hydroxytryptamine (5-HT) receptor mechanism, but the correlations between these independent mechanisms and pathological characterization were still unclear. To further explore the effect of Banxia Houpo decoction on known or unknown biological pathways during treatment of insomnia, the metabonomics method based on ¹H-NMR was developed for detecting the significant changes in metabolomics after the administration with Banxia Houpo decoction in pentobarbital sodium-induced rat sleeping experiment. Serum and urine samples were analyzed by ¹H-NMR. Principal component analysis (PCA) was carried out for endogenous small molecule metabolites in urine and serum. H-NMR spectroscopies and relevant metabolites were found and identified by Simca-p 17.0 (Umet-rics, Umea, Sweden) and Chenomx NMR Suite 7.1 (Chenomx, Inc., Edmonton, Alberta, Canada) software. The result suggests that Banxia Houpo decoction group and indiplon group had significant differences. The load diagram showed the biggest variation metabolites and intergroup significant differences among 10 metabolic substances. According to the experiment, Banxia Houpo decoction group and indiplon group can prolonge the sleeping time of pentobarbital sodium-induced sprague-dawley rats, with a synergistic effect. The significant changes of these biomarkers indicated that the Banxia Houpo decoction could aid sleep by adjusting the content of glutamine, creatine phosphate, 2-oxoglutarate, and reducing the activity of brain nerves.

Review for sedative and hypnotic mechanism of sedative traditional Chinese medicine and relative active components on neurotransmitters / 中国中药杂志

The sedative traditional Chinese medicine has a long history of clinical experience in treating insomnia. The main pharmacological effects of sedative agents are sedation, hypnosis, antianxiety and antidepression which might be related to certain neurotransmitters and cytokines and so on. This review summarized the mechanism of sedative traditional Chinese medicine and its active monomers based on neurotransmitters, including GABA, Glu, 5-HT, DA, NE and their metabolites 5-HIAA, HVA, DOPAC. The results showed that the most research about the sedative medicine at present was throught serotonergic and GABA ergic system. Study on Ziziphi Spinosae Semen was the most extensive, including its monomers, extracts and traditional Chinese patent medicines. It involved many sedative traditional Chinese medicine, such as Schisandrae Chinensis Fructus, Albiziae Flos, Polygalae Radix, Longan Arillus, Ganoderma, etc. It also systematically summarized the information which was useful for the further applications and research on sedative drugs and their active components.

Evaluation of the sedative and hypnotic effects of H057 / 中国药理学通报

Aim To investigate the sedative and hyp-notic effects of a novel compound H057 . Methods The sedative activity of H057 was investigated by re-cording the spontaneous locomotor activity in mice. The hypnotic property was evaluated by the latency and duration of loss of righting reflex( LORR) in mice and effect of H057 on the sleep onset in subthreshold dos-age of sodium pentobarbital treated mice. The extracel-lular levels of GABA and monoamine neurotransmitters in in cerebral cortex were measured by microdialysis in vivo. Results The spontaneous locomotor activity was decreased by 25% and 66% in H057 ( 5 , 25 mg · kg-1 ,i. p. ) treated mice, respectively. H057 ( 3, 5 mg·kg-1 ,i. p. ) increased the sleep onset to 62. 5%and 87. 5% in subthreshold dosage of sodium pentobar-bital(25 mg·kg-1,i. p. ) treated mice. H057(≥60 mg· kg-1 , i. p. ) could completely induce LORR in mice. The latency of LORR at dose of 60 mg · kg-1 was (24 ± 11) min and the duration of LORR was (96 ± 15 ) min. In vivo mircodialysis revealed that H057 (25 mg·kg-1 , i. p. ) could significantly increase the GABA level by 26% and decrease the 5-HT and NE levels by 50% and 38% in cerebral cortex in mice. Conclusion H057 has potent sedative and hypnotic effects, which may be closely related to the increased content of GABA and the decreased contents of 5-HT and NE in the extracellular fluid in cerebral cortex.

Hypnotic effects of a novel anti-insomnia formula on Drosophila insomnia model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants.</p><p><b>METHODS</b>Caffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period.</p><p><b>RESULTS</b>AIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants.</p><p><b>CONCLUSION</b>AIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.</p>

An Experimental Study on Pharmacodynamics and Mechanism of Sedative-hypnotic Effect ofTiaozhong Huatan Anshen Mixture / 中国中医药信息杂志

Objective To explore the mechanism ofTiaozhong Huatan Anshen Mixture (THAM). Methods A total of 200 healthy Kunming mice were randomly and equally divided into first, second, third and fourth major groups. Each major group was further equally divided into blank group, control group and high, medium, low dose THAM groups. Each group was given an equal volume of NS, estazolam, or high, medium, or low dose THAM by gavage for 7 d. For the first major group, the changes in number of spontaneous activities after administration were evaluated. For the second major group, 60 min after administration, each group was given pentobarbital sodium (30 mg/kg body weight, minimum dose for all mice sleeping) by intraperitoneal injection, and the sleep time was recorded. For the third major group, 60 min after administration, each group was given pentobarbital sodium (15 mg/kg body weight, maximum dose for 90%-100% of all mice having righting reflex) by intraperitoneal injection. The number of mice falling asleep was recorded, and the sleep rate was calculated. For the fourth major group, mice were sacrificed after continuous administration 15 d. They were quickly removed brain tissue;homogenates were taken out in batches;5-HT and 5-HIAA levels in brain tissues were determined according to fluorescence spectrophotometric.Results Compared with the blank group, all treated groups had a reduced number of spontaneous activities, a shortened sleep latency, a prolonged sleep time, and an increased sleep rate after administration (P0.05). Compared with the blank group, brain 5-HT and 5-HIAA levels in all treated groups increased in mice (P<0.01,P<0.05), with the most significant changes seen in the high-dose THAM group (P<0.05).Conclusion THAM has a significant sedative-hypnotic effect. The mechanism may be related to increasing brain 5-HT synthesis and metabolism.

Research on hypnotic and anticonvulsant activities of total alkaloids in leaves of eucommia ulmoides / 中草药·英文版

Objective: To study the hypnotic and anticonvulsant activities of the leaves of Eucommia ulmoides (LEU), the total alkaloids were extracted from LEU using water-acid method. Methods: Mice were divided into five groups, including groups contained total alkaloids in three different doses, negative and positive control groups. Direct hypnotic experiment in mice, pentobarbital sodium synergistic experiment, and anticonvulsant experiment were used. The numbers of spontaneous activities, sleep rate, sleep latency, sleep time, convulsion rate, and convulsion latency of the mice were recorded and analyzed. Results: The total alkaloids from LEU could increase the sleep rate, significantly lengthen the sleep time, and shorten the sleep latency of mice. Even the low dose of total alkaloids (0.33 g/kg) showed significantly different activities with negative control group (physiological saline) with the synergistic effect of the superthreshold dose of pentobarbital sodium. Furthermore, the total alkaloids efficiently inhibited the convulsion caused by nikethamide. Conclusion: The total alkaloids from LEU have the excellent sedative, hypnotic, and anticonvulsant activities in mice, with high safety and little drug side effects. Therefore, they have the protential development prospects in sedative-hypnotic drugs. © 2014 Tianjin Press of Chinese Herbal Medicines.