The anxiolytic and circadian regulatory effect of agarwood water extract and its effects on the next generation; zebrafish modelling.

Anxiety is one of the most common psychiatric symptoms worldwide. Studies show that there is an increase of >25 % in the prevalence of anxiety with the onset of the COVID-19 pandemic process. Due to the various side effects of drugs used in the treatment of anxiety, interest in natural therapeutic alternatives has increased. Agarwood is a plant used as a natural therapeutic due to its sedative effect as well as many effects such as antioxidant and antibacterial. Although there are many studies with agarwood, comprehensive behavioral studies, including the next generation, are limited. In present study, zebrafish fed with diets containing 10-100 ppm water extract of Agarwood (AWE) for 3 and 8 weeks were exposed to predator stress using Oscar fish in order to test the potential anxiolytic effect of AWE. At the end of the period, zebrafish exposed to predator stress were subjected to anxiety and circadian tests. Histopathological evaluation and immunofluorescent analyzes of BDNF and 5HT4-R proteins were performed in the brains of zebrafish. The effects on the next generation were examined by taking offspring from zebrafish. According to the results, it was observed that AWE had a healing effect on anxiety-like behaviors and on the disrupted circadian rhythm triggered by the predatory stress it applied, especially in the 8 weeks 100 ppm group. Interestingly, it was also found to be effective in offspring of zebrafish fed diets with AWE.

Overlooked switch from transient sedation to sustained excitement in the Biphasic effects of Ephedra Herb extract administered orally to mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In our previous study, we reported that Ephedra Herb extract (EHE) increased the locomotor activity of mice in the open-field test and reduced the immobility time in the forced swim test. Ephedrine alkaloids (EAs) are thought to be responsible for the adverse effects of Ephedra Herb. However, there are no reports to verify that the adverse effects of Ephedra Herb are caused by the amount of EAs in the herb. Therefore, we investigated whether these adverse effects of EHE are caused by the amounts of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract. In a preliminary study of the time course analysis of the open field test, we newly observed that EHE evoked switching from transient sedation to sustained excitement. AIM OF THE STUDY: We aimed to confirm whether EHE evokes switching from transient sedation to sustained excitement, investigate whether these actions of EHE are caused by the amount of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract, and clarify the molecular mechanism of the transient sedative effect. MATERIALS AND METHODS: The locomotor activity of mice was tested using the open-field test. The immobility times were measured using a forced swim test, and the motor dysfunction in mice was tested using the rotarod test. RESULTS: EHE, Eph, and Pse induced transient motionlessness between 0 and 15 min after oral administration, however, they did not induce depression-like behavior and motor dysfunction in mice, suggesting that the motionlessness induced by EHE, Eph, or Pse resulted from sedation. The α2a adrenoceptor inhibitor, atipamezole, decreased their sedative effects. Thus, immediately after EHE administration, the transient sedative effect is mediated through the activation of the α2a adrenoreceptor by Eph and Pse. EHE and Eph increased total locomotor activity for 15-120 min after oral administration; however, Pse had no effect. Therefore, the slow-onset and sustained excitatory effects of EHE are mediated by Eph. CONCLUSIONS: We discovered for the first time that EHE evokes diphasic action by switching from transient sedation to sustained excitement. The transient sedation was evoked by the Eph and Pse in the herbal extract via activation of the α2a adrenoceptor and the sustained excitement was caused by the Eph in the herbal extract.

Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III).

Rationale: The SPICE III (Sedation Practice in Intensive Care Evaluation) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation. Objectives: To quantify the association of different infusion rates of dexmedetomidine and propofol, given in combination, with mortality and to determine if this is modified by age. Methods: We included 1,177 patients randomized in SPICE III to receive dexmedetomidine and given supplemental propofol, stratified by age (>65 or ⩽65 yr). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality. Measurements and Main Results: Younger patients (598 of 1,177 [50.8%]) received significantly higher doses of both sedatives compared with older patients to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 µg/kg/h) was associated with reduced adjusted mortality in younger but not older patients. This was consistent with multivariable regression modeling (hazard ratio, 0.59; 95% confidence interval, 0.43-0.78; P < 0.0001) adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients, using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality (hazard ratio, 1.30; 95% confidence interval, 1.03-1.65; P = 0.029). Conclusions: In patients ⩽65 years of age sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registered with www.clinicaltrials.gov (NCT01728558).

The combined analgesic, sedative, and anti-gastric cancer mechanisms of Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo based on integrated ethnopharmacological data.

ETHNOPHARMACOLOGY RELEVANCE: As a Yi medicine for eliminating wind to relieve pain, Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo (TSY) is widely used to treat sore throat, stomach pain, bone and muscle injuries, and tumors; however, the material basis and mechanism of action remain unclear. AIM OF THE STUDY: This study aims to investigate the potential active compounds of TSY and related pharmacological mechanisms against gastric cancer using a multitarget strategy. MATERIALS AND METHODS: The main chemical components of TSY were collected through a literature review and database searches. The components were further screened for ADMET properties, and their targets were predicted using network pharmacology (admetSAR) and substructure-drug-target network-based inference (SDTNBI) approaches in silico. The pharmacological mechanism of action of TSY extract for pain relief, sedation, and anti-gastric cancer activities were identified via in vivo and in vitro biochemical analyses. RESULTS: Here, 28 chemical components were identified, 7 active compounds were selected, and 75 targets of TSY extract were predicted. A compound-target-disease network topological approach revealed that the predicted targets are highly related to the digestive system and nervous system. Network pharmacology results suggested that the anti-gastric cancer activity of TSY was highly correlated with its analgesic and sedative targets and MAPK. In vivo experiments confirmed that TSY extract not only reduced the number of voluntary activities in the mouse model but also exhibited a synergistic effect on sodium pentobarbital-induced sleep, reduced the number of mice exhibiting writhing responses to acetic acid, and increased the hot plate pain threshold of mice. Thus, TSY extract exhibits good analgesic and sedative effects. The TSY extract inhibited HGC-27 cell proliferation and induced apoptosis by regulating apoptotic proteins (BAX, BCL-2 and BCL-XL) in vitro. CONCLUSIONS: TSY exhibits combined analgesic, sedative, and anti-gastric cancer activities.

Combination of Dexmedetomidine and Tramadol in Patient-Controlled Intravenous Analgesia Strengthens Sedative Effect in Pregnancy-Induced Hypertension.

Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH). Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated. Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased. Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis.

Allergic rhinitis (AR) is the most common undiagnosed chronic condition in children. Moderate/severe AR symptoms significantly impair quality of life, and cause sleep disruption, absenteeism and decreased productivity. Additionally, untreated AR predisposes children to asthma and other chronic conditions. Although intranasal corticosteroids are the most effective pharmacologic treatment for AR, oral antihistamines are often preferred. First-generation antihistamines may be chosen to relieve AR symptoms as they are inexpensive and widely available; however, they cause sedative and cardiovascular negative effects due to poor receptor selectivity. Therefore, second-generation antihistamines were developed to reduce adverse effects while retaining efficacy. There are fewer clinical trials in children than adults, therefore, efficacy and safety data is limited, particularly in children under 6 years, highlighting the need to generate these data in young children with AR. Fexofenadine, a highly selective second-generation antihistamine, effectively alleviates symptoms of AR, is non-sedating due to decreased blood-brain barrier permeability, and is devoid of cardiovascular side effects. Importantly, fexofenadine relieves the ocular symptoms of allergic conjunctivitis, which occur concomitantly with AR, improving quality of life. Overall, fexofenadine displays a favorable safety profile and results in greater treatment satisfaction in children compared with other second-generation antihistamines. This review aimed to evaluate and compare the safety and efficacy of fexofenadine with other available first- and second-generation antihistamines in children with AR.

Essential Oil from the Leaves of Chromolaena odorata, and Sesquiterpene Caryophyllene Oxide Induce Sedative Activity in Mice.

Chromolaena odorata (L.) R.M.King & H.Rob. essential oil (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and the most efficient concentrations were 0.04 and 0.00004 mg/cage (volume of the cage 61.2L). Analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound and bioactivity-guided fractionation of the oil was performed to isolate the compound responsible for activity. The data clearly identified sesquiterpene caryophyllene oxide as the compound inducing COEO sedative activity and it was effective in decreasing mice locomotor activity by 56% and 57% at 0.0004 and 0.04 mg/cage, respectively. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the central nervous system (CNS) by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results showed that caryophyllene oxide is a potent CNS depressant. Nevertheless, it fails to potentiate the effects of pentobarbital on the GABAergic system, nor did flumazenil, a GABAA receptor antagonist, reversed its effects. It was especially interesting to note that ß-caryophyllene, the precursor of caryophyllene oxide, demonstrated a similar pattern of sedative activity, and the present work further extends actual knowledge on these naturally occurring sesquiterpenes. The findings in this study reveal the new activity of caryophyllene oxide as an innovative way to manage sleep and CNS-related disorders, and demonstrates a satisfactory effect of two interesting sesquiterpene compounds on the CNS.

Sedative-hypnotic effect and in silico study of dinaphthodiospyrols isolated from Diospyros lotus Linn.

Traditionally, Diospyros lotus Linn is used for insomnia and other associated disorders. Insomnia is a worldwide disorder with different etiology which is treated with different synthetic medicine associated with addiction. Natural products are generally devoid of such addition with good efficacy. Current research was conducted to evaluate the sedative and hypnotic effects of dimeric naphthoquinones such as dinaphthodiospyrol A (1), dinaphthodiospyrol B (2), dinaphthodiospyrol C (3), dinaphthodiospyrol D (4), dinaphthodiospyrol E (5) and dinaphthodiospyrol F (6) isolated from the chloroform fractions of D. lotus. The sedative and hypnotic effects at the dose of 5 and 10 mg/kg (each compound) were assessed through open field and phenobarbital induced sleep test, respectively. In the case of open field test the administration of tested compounds significantly hindered the movement of animals, while in case of hypnotic effect the tested samples significantly improved the onset and duration of sleep as compared to control. The overall effects were in a dose dependent manner. The compounds were also assessed for acute toxicity, but no toxicity was observed. In this regard, our research triumphantly announced the strong chemical base for the folkloric values of the plant with their fringe benefits and implemented a platform for further aspects of mechanistic and clinical studies. A possible mechanism of in vivo inhibition was studied by using docking simulations on GABA receptors. Binding orientations and types of interactions revealed that a possible mechanism behind these pharmacological actions might be interaction with GABA receptors.

Effect of age on dexmedetomidine treatment for ventilated patients with sepsis: a post-hoc analysis of the DESIRE trial.

AIM: There are no definitive data to determine whether age influences the effects of dexmedetomidine (DEX) treatment. Thus, we investigated whether older age was associated with more favorable sedative action by DEX in sepsis patients who required mechanical ventilation. METHODS: This study involved a post-hoc analysis of data from the Dexmedetomidine for Sepsis in the ICU Randomized Evaluation (DESIRE) trial. The patients were categorized based on median age into elderly and younger groups. The two groups were then compared during the first 7 days after ventilation based on proportion of patients with well-controlled sedation (Richmond Agitation-Sedation Scale score between -3 and +1), days free from delirium (based on the Confusion Assessment Method for ICU), and days free from coma (Richmond Agitation-Sedation Scale score between -4 and -5). RESULTS: One hundred and one patients were assigned to the elderly group and 100 patients were assigned to the younger group. In the elderly group, 50 patients received DEX treatment and 51 patients received non-DEX treatment, with the DEX arm having significantly better-controlled sedation (range, 14-52% versus 16-27%; P = 0.01). In the younger group, 50 patients received DEX treatment and 50 patients received non-DEX treatment, with no significant difference in the proportions of well-controlled sedation (range, 20-64% versus 24-60%; P = 0.73). There were no significant differences in the numbers of days free from delirium or coma between the groups. CONCLUSION: In elderly sepsis patients who require ventilation, dexmedetomidine could be more effective than other sedative agents for achieving proper sedation.

Sedative effects of inhaled Perilla frutescens essential oils on mice.

Perilla frutescens is an ingredient for cooking and for Japanese traditional medicine formulations. Essential oils extracted from P. frutescens are classified according to their composition, which are genetically regulated. Here, we extracted five types of essential oil from P. frutescens and studied their sedative activities. We grew P. frutescens strains that give oils of type PK, PA, PP, EK, and C, and extracted the essential oils by hydrodistillation. We then measured the spontaneous locomotor activity of mice who had inhaled the oils in an open field test. All types of essential oil except the PK type decreased the spontaneous locomotor activity of mice. The effective doses were 4.0 × 10-3 to 4.0 × 10-2 mg/cage (PA type), 4.0 × 10-4 mg/cage (PP type), 4.0 × 10-5 mg/cage (EK type), and 4.0 × 10-5 to 4.0 × 10-3 mg/cage (C type). Our results show that the essential oils of type PA, PP, EK, and C have a sedative effect.

Sedative effects of l-menthol, d-camphor, phenylethyl alcohol, and geraniol.

Various essential oils from plants and fragrance components such as monoterpenes have been discovered to reduce spontaneous movements in mice; thus, it has been made clear that the odor itself has the sedative activity. In the present study, we examined the sedative activity of the odors of fragrance components added to eye drops; l-menthol, d-camphor, phenylethyl alcohol, and geraniol, which are often used as refreshers or preservatives. Each fragrance component was administered by the inhalation route to mice, and the sedative effects were evaluated using an open field test. The results showed that four components administered via inhalation to mice significantly decreased the amount of spontaneous motor activity in a dose-dependent manner, indicating that all four components have a sedative effect. The optimal concentrations at which l-menthol, d-camphor, phenylethyl alcohol, and geraniol showed the highest sedative activity were 4 × 10-2 mg per cage, 4 × 10-4 mg per cage, 4 × 10-2 mg per cage, and both 4 × 10-4 and 4 × 10-2 mg per cage, respectively. The AUC graph of geraniol was represented as a W-shaped curve, suggesting that the sedative action of geraniol was biphasic. The present finding demonstrates a new perspective on a possible pharmacological property of eye drop additives used with no expected pharmacological functions.

Rehospitalization Risk of Receptor-Affinity Profile in Antipsychotic Drug Treatment: A Propensity Score Matching Analysis Using a Japanese Employment-Based Health Insurance Database.

PURPOSE: The aim of this study was to examine whether there is a difference in the risk of rehospitalization when antipsychotics are classified into two groups treated using drugs with a higher or lower affinity to H1 or α1 receptors than to D2 receptors (histamine H1 receptors, adrenaline α1 receptors [HA] high- and HA low-affinity drug group, respectively) based on affinity to receptors related to sedation using a nationwide insurance claims database in Japan. PATIENTS AND METHODS: We identified eligible patients by the following two criteria: (i) hospitalization due to schizophrenia (International Classification of Disease [ICD]-10 code: F20 or F25) in psychiatric wards between January 1st, 2005 and August 31st, 2017, and (ii) administration of HA high- or HA low-affinity drugs in the next month after discharge from the earliest hospitalization due to schizophrenia (index month). The primary endpoint was rehospitalization due to schizophrenia. The secondary endpoints were (i) involuntary rehospitalization, (ii) concomitant use of anxiolytics/hypnotics, mood stabilizers, and antiparkinsonian drugs, (iii) all-cause death, and (iv) medication discontinuation. Propensity score (PS) matching analysis was applied, and the hazard ratio (HR) of the event rate in the HA high-affinity drug group relative to the HA low-affinity drug group was calculated using Cox's proportional hazards model. RESULTS: Two thousand nine hundred and forty patients were identified as eligible patients. Among PS-matched patients (819 in each group), the HR in the HA high-affinity drug group compared with the HA low-affinity drug group was 1.018 (0.822-1.260, P = 0.870). Other outcomes did not differ significantly between the two groups. CONCLUSION: No significant difference was observed in the rehospitalization risk due to schizophrenia associated with HA high-affinity antipsychotic drugs. Although this study was a retrospective PS-matched cohort study, the possibility of masking of the rehospitalization risk cannot be excluded because more than 80% of the patients were administered an anxiolytic/hypnotic at the time of admission.

Nano-emulsification of Aeollanthus suaveolens Mart. Ex Spreng essential oil modifies its neuroeffects?

Oil in water nano-emulsions are drug delivery systems constituted by liquid lipophilic nano-droplets dispersed through the external aqueous phase, often reaching the kinetic stability with surfactant as stabilizers. Essential oils can be the oily phase or the source of bioactive compounds. In this study, the essential oil of Aeollanthus suaveolens-a plant used in folk medicine due to its psychopharmacological effects-was used for preparation of fine nano-emulsions by a low-energy titrating method. Monodisperse small nano-droplets (ca. 70 nm; PdI 0.200) were assembled by using blends of non-ionic surfactants, indicating modulation on surfactant system lead to altering the physical property. In a separate set of experiments, we investigated the role of this modulation on biological properties of the optimal nano-emulsion. The zebrafish embryos were more susceptible to the nano-emulsion than the bulk essential oil, showing the improved bioactivity due to nano-sizing. Therefore, adult zebrafish was treated, and paralysis was observed in the groups treated with the nano-emulsion, being this finding in accordance with hypnosis. At the same essential oil dose, another behavior was observed, suggesting that expected dose-dependent effects associated to sedative-hypnotics can be achieved by nano-sizing of psychoactive essential oils. This paper contributes to the state-of-art drug delivery systems by opening perspectives for novel sedative-hypnotics nano-emulsified essentials oils that can reach hypnotic effects at considerably lower dose, when compared with bulk materials, being useful for further completed dose-response studies.Graphical abstract.

Glaucacetalin E and galphimidin B from Galphimia glauca and their anxiolytic activity.

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 CHCl3 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 CHCl3 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.

Sedative Effects of Latexes Obtained from Some Lactuca L. Species Growing in Turkey.

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 Pancic) 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, 11,13ß-dihydrolactucin, and 11,13ß-dihydrolactucopicrin) were determined qualitatively and quantitatively by high-performance liquid chromatography (HPLC). Lactucin was identified as the main component.

Sedative effects of the essential oil from the leaves of Lantana camara occurring in the Republic of Benin via inhalation in mice.

Lantana camara Linn. (Verbenaceae) is used traditionally for its numerous medicinal properties such as antimalarial, antibacterial, anticancer and anti-inflammatory. In the present study, we investigated the chemical composition of essential oil from the leaves of L. camara (LCEO) occurring in the Republic of Benin (West Africa) in comparison with LCEOs from other regions; evaluated its sedative effects in mice via inhalation administration; and identified the compounds responsible for activity. LCEO was extracted by hydrodistillation and chemical analyses of the oil were performed by GC and GC/MS. The oil was dominated by monoterpene hydrocarbons (60.58%) and oxygenated monoterpenes (33.39%), among which sabinene (38.81%) and 1,8-cineole (28.90%) were the most abundant. LCEO administered via inhalation to mice significantly decreased locomotor activity in a dose-dependent manner, mainly at the doses of 0.0004 and 0.04 mg per 400 µL of triethyl citrate (TEC). The oil was fractionated to give two fractions, which were further investigated, and revealed that both sabinene and 1,8-cineole were the principal active compounds. The results of the present study indicated that via inhalation administration, LCEO and its main constituents could be considered as promising candidates for the management of dementia, insomnia, attention deficit hyperactivity disorder and other central nervous system-associated diseases.

[Pharmacological mechanism of traditional sedative effect of alkaloids in Nelumbinis Plumula based on network pharmacology].

Nelumbinis Plumula has the traditional sedative effect,but its mechanism is unclear. In this study,the relationship between traditional sedative effect and hypnotic effect of Nelumbinis Plumula was taken as the starting point to study the hypnotic mechanism of the major medicinal components in Nelumbinis Plumula by the network pharmacology method. Targets of active Nelumbinis Plumula alkaloids were screened by Swiss Target Prediction server,TCMSP and BATMAN-TCM. Targets of hypnotic drugs approved by FDA were screened from Drug Bank,OMIM,TTD databases. The common targets were screened by GO and KEGG pathways. Cytoscape 3. 7. 1 software was used to construct the network of " active component-target-pathway-disease". The results of network analysis showed that 21 active compounds were associated with 44 targets and 28 pathways. Among them,21 compounds,35 targets and 15 pathways were predicted to be related to sedative hypnosis. Nelumbinis Plumula showed the hypnotic effect by acting on neuroactive ligand-receptor interaction pathway,regulation of actin cytoskeleton pathway,calcium signaling pathway,cholinergic synapse pathway.This study preliminarily revealed the potential active compounds and possible mechanisms of traditional sedative effect of Nelumbinis Plumula,which provided a theoretical basis for further experimental studies on medicinal materials and its mechanisms.

Effects of the Hyptis martiusii Benth. leaf essential oil and 1,8-cineole (eucalyptol) on the central nervous system of mice.

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.

Instant sedative effect of acupuncture at GV20 on the frequency of electroencephalogram α and ß waves in a model of sleep deprivation.

Sleep deprivation (SD) adversely affects brain function and is accompanied by frequency-dependent changes in electroencephalograms (EEGs). Recent studies have suggested that acupuncture is an emerging alternative therapy for SD. However, the involvement of the frequency of EEG α and ß waves in the protective effect of acupuncture against SD remains unknown. The present study investigated the instant effect of acupuncture at GV20 on insomnia by analyzing the frequency of α and ß waves using electroencephalography in a model of sleep deprivation. A total of 16 rats (Wistar; male; weight, 340±10 g) were divided randomly into four groups (4 rats per group) to create a rat model of sleep deprivation using the modified multiple platform method in the GV20 group, the sham acupoint group and the model group. After 72 h of sleep deprivation for these three groups and normal feeding for the blank group, the EEG data of all four groups were documented. Following the initial measurement, the GV20 group was treated by acupuncture at GV20 and the sham acupoint group was treated at the sham acupoint, and their EEGs were recorded during the treatment. The frequency of α and ß waves of all EEG data were analyzed. Prior to intervention, the GV20 group, the sham acupoint group and the model group exhibited no significant differences in α and ß wave frequencies; however, the α wave frequency of these three groups was significantly decreased compared with the blank group (P<0.05), whereas the ß wave frequency of these three groups was significantly increased compared with the blank group (P<0.05). This suggested that sleep deprivation affected the frequency of brain waves and enhanced the excitability of the cerebral cortex. During acupuncture treatment with retained needle conditioning, the GV20 group indicated a significant increase in α wave frequency (P<0.05), as well as a significant decrease in ß wave frequency compared with prior to treatment (P<0.05), whereas the sham acupoint group exhibited no significant changes. The present findings from a rat model of sleep deprivation suggested that acupuncture treatment at GV20 may reduce the excitability of the brain cortex. Due to its sedative effect, treatment at GV20 may be considered for the treatment of insomnia and related symptoms.

Sedative-hypnotic and anxiolytic effects and the mechanism of action of aqueous extracts of peanut stems and leaves in mice.

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.