• The Korean Journal of Food And Nutrition
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• v.30 no.6
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• pp.1364-1369
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• 2017

There is a growing demand for natural sleep aids due to various side effects of long-term administration of pharmacological treatments for insomnia. Honey has been reported to exhibit numerous potential health benefits, and it is hypothesized that honey may favorably affect insomnia treatment. Therefore, this study was performed to investigate the possible hypnotic effect of clover honey (CH) and to determine its in vivo mechanism. The total flavonoid content (TFC) of CH and fractions extracted with ethylacetate (EtOAc) and $H_2O$ was measured. The pentobarbital-induced sleep test using $GABA_A$-benzodiazepine (BZD) agonists and antagonists was conducted to evaluate the potential mechanism of action behind the sedative-hypnotic activity of CH in mice. The results showed that administration of 500 and 1,000 mg/kg of CH significantly (p<0.01) reduced the sleep latency to a level similar to that of diazepam (DZP, 2 mg/kg), and 1,000 mg/kg of CH significantly (p<0.01) prolonged the sleep duration, which was comparable to that of DZP (2 mg/kg). Administration of the EtOAc fraction with a higher TFC significantly reduced the sleep latency at 50 to 200 mg/kg and prolonged the sleep duration at 100 to 200 mg/kg, which were comparable to those after administration of DZP (2 mg/kg). However, co-administration of CH and EtOAc with flumazenil, a specific $GABA_A-BZD$ receptor antagonist, blocked the hypnotic effect. Our findings suggest that the hypnotic activity of CH may be attributed to allosteric modulation of $GABA_A-BZD$ receptors. The TFC of CH is expected to be a key factor that contributes to its hypnotic effect.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.531-539
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• 2024

Sleep is one of the most essential physiological phenomena for maintaining health. Sleep disturbances, such as insomnia, are often accompanied by psychiatric or physical conditions such as impaired attention, anxiety, and stress. Medication used to treat insomnia have concerns about potential side effects with long-term use, so interest in the use of alternative medicine is increasing. In this study, we investigated the hypnotic effects of β-lapachone (β-Lap), a natural naphthoquinone compound, using pentobarbital-induced sleep test, immunohistochemistry, real-time PCR, and western blot in mice. Our results indicated that β-Lap exerts a significant hypnotic effect by showing a decrease in sleep onset latency and an increase in total sleep time in pentobarbital-induced sleep model. The results of c-Fos immunostaining showed that β-Lap decreased neuronal activity in the basal forebrain and lateral hypothalamus, which are wakefulness-promoting brain regions, while increasing in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A₁ receptor (A₁R) antagonist. Western blot analysis showed that β-Lap increased extracellular signal-regulated kinase phosphorylation and nuclear factor-kappa B translocation from the cytoplasm to the nucleus; these effects were inhibited by DPCPX. Additionally, β-Lap increased the mRNA levels of A₁R. Taken together, these results suggest that β-Lap exerts hypnotic effects, potentially through A₁R.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.4
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• pp.241-251
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• 2017

Devices that monitor the depth of hypnosis based on the electroencephalogram (EEG) have long been commercialized, and clinicians use these to titrate the dosage of hypnotic agents. However, these have not yet been accepted as standard monitoring devices for anesthesiology. The primary reason is that the use of these monitoring devices does not completely prevent awareness during surgery, and the development of these devices has not taken into account the neurophysiological mechanisms of hypnotic agents, thus making it possible to show different levels of unconsciousness in the same brain status. An alternative is to monitor EEGs that are not signal processed with numerical values presented by these monitoring devices. Several studies have reported that power spectral analysis alone can distinguish the effects of different hypnotic agents on consciousness changes. This paper introduces the basic concept of power spectral analysis and introduces the EEG characteristics of various hypnotic agents that are used in sedation.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.584-590
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• 2019

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptorbenzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with $IC_{50}$ of 1.19, $0.84{\mu}g/kg$, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4261-4264
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• 2014

Objective: To examine the prescription rates in cancer patients of three common psychotropic drugs: anxiolytic/hypnotic, antidepressant and antipsychotic. Materials and Methods: In this retrospective cohort study, data were extracted from the pharmacy database of University Malaya Medical Center (UMMC) responsible for dispensing records of patients stored in the pharmacy's Medication Management and Use System (Ascribe). We analyzed the use of psychotropics in patients from the oncology ward and cardiology from 2008 to 2012. Odds ratios (ORs) were adjusted for age, gender and ethnicity. Results: A total of 3,345 oncology patients and 8,980 cardiology patients were included. Oncology patients were significantly more often prescribed psychotropic drugs (adjusted OR: anxiolytic/hypnotic=5.55 (CI: 4.64-6.63); antidepressants=6.08 (CI: 4.83-7.64) and antipsychotics=5.41 (CI: 4.17-7.02). Non-Malay female cancer patients were at significantly higher risk of anxiolytic/hypnotic use. Conclusions: Psychotropic drugs prescription is common in cancer patients. Anxiolytic/hypnotic prescription rates are significantly higher in non-Malay female patients in Malaysia.

• Sleep Medicine and Psychophysiology
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• v.7 no.1
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• pp.5-9
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• 2000

Several nonpharmacological treatment methods of insomnia and their effects were reviewed. A long-term use of most hypnotics may produce tolerance, dependence, cognitive and psychomotor impairments at daytime, shallow sleep, and rebound insomnia on drug withdrawal. To reduce hypnotic abuse, nonpharmacological strategies have been developed to correct disordered behavioral and cognitive factors. These treatments aim at modifying maladaptive sleep habits, lowering physiological and cognitive arousal levels, and correcting dysfuctional beliefs and attitudes about sleep. These non-pharmacological or cognitive behavior treatments include stimulus control, sleep restriction, relaxation training, sleep hygiene education, cognitive therapy, and light therapy. Among them the stimulus control therapy has been demonstrated most effective as a single treatment or in combination with other treatments. Through nonpharmacological treatments, sleep latency was most significantly reduced and wake time after sleep onset was also reduced. About 50% of insomniacs reported clinical improvements in terms of nearly normalized sleep latency, awakening time, sleep efficiency, and reduction of hypnotic use. Compared to the hypnotic therapy, nonpharmacological treatments are more cost-effective and more readily accepted by patients, and their effects last longer.

• Natural Product Sciences
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• v.9 no.2
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• pp.91-92
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• 2003

The present investigation was carried out to evaluate the antinociceptive and sedative - hypnotic effect of a vacuum dried methanol extract of aerial parts of Artemisia pallens. In the tail-flick method with Swiss albino mice the methanol extract at the doses of (1500 mg/kg, 2000 mg/kg, and 2500 mg/kg) showed significant antinociceptive activity. Significant potentiation of Pentobarbitone sodium - induced sleeping time was observed in mice on co-administration of the various doses of the methanol extract of Artemisia pallens.

• The Korean Journal of Physiology
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• v.6 no.1
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• pp.27-31
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• 1972

The activity of Mg and Na-K activated ATPase of homogenate from rat brain cortex was measured in vitro under the variety of conditions. The effects of various hypnotic and tranquilizer such as phenobarbital, amobarbital, diazepam, promazine and chlorpromazine on the activities of both ATPase was investigated and the results was summarized as follows. 1. Na-K ATPase was slightly inhibited by phenobarbital and amobarbital while Mg ATPase was moderately activated by these drugs. 2. Both Mg and Na-K ATPase activities were markedly inhibited by diazepam. 3. Promazine and chlorpromazine markedly inhibited both Mg and Na-K ATPase activities. These findings indicate that remarkable correlation between hypnotic or tranquilizing potency and ATPase inhibition could be observed.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.314-320
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• 2014

This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via ${\gamma}$-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of $GAD_{65/67}$ over a broader range of doses. PA increased ${\alpha}$- and ${\beta}$-subunits protein levels, but decreased ${\gamma}$-subunit protein levels in $GABA_A$ receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via $GABA_A$-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.

• The Korean Journal of Pharmacology
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• v.10 no.1 s.15
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• pp.61-65
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• 1974

Berberis koreana Palibin belonging to Berberidaceae family, a common herb in Korea, has been contained some quantity of Berberine analogue and other ingredients. Authors therefore paid attention to its pharmacological actions and examined the effects on sleep duration and rectal temperature in mouse with crystal (A) from Berberis koreana Palibin in Korean native plans. The experiment searching for the effect on sleep duration was performed with pretreatment of Berberis Koreana Palibin crystal (A) 30 min before the administration of 25 % ethanol, and its crystal were also administered intraperitoneally with the intention to examine the effect on rectal temperature in mouse. The results of the experiment were as follows; 1. Crystal (A) from Berberis koreana Palibin was made by extraction with ethanol and HCI. 2. Crystal (A) enhanced the hypnotic activity of alcohol in concentratins of 0.1 mg/10g or 0.15 mg/10g. 3. Rectal temperatures in mice were significantly reduced with administration of crystal (A) in concentrations of 0.1 mg/10g or 0.15 mg/10g. 4. The maximal reduction of rectal temperature and potentiation of the hypnotic activity were observed at 30 min after its administration. From the above results, it is clear that crystal (A) from Berberis koreana Palibin exerts the potentiation of hypnotic action of alcohol and reduction of rectal temperature in normal mouse. Its pharmacological effects are probably derived from the action upon the central nervous system.