• Journal of Ginseng Research
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• v.36 no.4
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• pp.403-410
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• 2012

The current inquiry was conducted to assess the change in sleep architecture after long periods of administration to determine whether ginseng can be used in the therapy of sleeplessness. Following post-surgical recovery, red ginseng extract (RGE, 200 mg/kg) was orally administrated to rats for 9 d. Data were gathered on the 1st, 5th, and 9th day, and an electroencephalogram was recorded 24 h after RGE administration. Polygraphic signs of unobstructed sleep-wake activities were simultaneously recorded with sleep-wake recording electrodes from 11:00 a.m. to 5:00 p.m. for 6 h. Rodents were generally tamed to freely moving polygraphic recording conditions. Although the 1st and 5th day of RGE treatment showed no effect on power densities in nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, the 9th day of RGE administration showed augmented ${\alpha}$-wave (8.0 to 13.0 Hz) power densities in NREM and REM sleep. RGE increased total sleep and NREM sleep. The total percentage of wakefulness was only decreased on the 9th day, and the number of sleep-wake cycles was reduced after the repeated administration of RGE. Thus, the repeated administration of RGE increased NREM sleep in rats. The ${\alpha}$-wave activities in the cortical electroencephalograms were increased in sleep architecture by RGE. Moreover, the levels of both ${\alpha}$- and ${\beta}$-subunits of the ${\gamma}$-aminobutyric acid $(GABA)_A$ receptor were reduced in the hypothalamus of the RGE-treated groups. The level of glutamic acid decarboxylase was over-expressed in the hypothalamus. These results demonstrate that RGE increases NREM sleep via $GABA_A$ergic systems.

• Journal of Ginseng Research
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• v.32 no.3
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• pp.220-225
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• 2008

The present investigation was performed to evaluate the homeostatic regulation of sleep architecture by the ethanol extract of Korea red ginseng (KRG), since the available data were often controversial. In addition, it was also interested in whether the sleep-wake stages were differently affected by low and high doses of KRG. Each adult Wistar male rat was implanted with a transmitter for recording EEG and activity via telemetry. After one week of surgery, polygraphic signs of undisturbed sleep-wake activities were recorded for 12 h (between 9:00 am and 9:00 pm) after KRG administration. KRG (10 and 100 mg/kg) increased non-rapid eye movement (NREM) sleep as well as total sleep. The total percentages of wakefulness were decreased comparably. KRG (10 mg/kg) decreased the power density of the ${\delta}-wave$ (0.75-4.5 Hz) and increased ${\alpha}-wave$ (8.0-13.0 Hz) in the NREM and rapid eye movement (REM) sleep. KRG also decreased ${\delta}-wave$ power density in wake time. However, KRG (100 mg/kg) increased ${\delta}-wave$ and decreased ${\theta}-wave$ (5.0-9.0 Hz) power density in wake time, while showed little effect on the power density in NREM and REM sleep. In conclusion, low and high doses of KRG increase spontaneous sleep and NREM sleep and differently regulate the EEG spectra in REM and NREM sleep.

• Natural Product Sciences
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• v.15 no.4
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• pp.213-221
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• 2009

Longanae Arillus (the rind of fruits of Dimocarpus longan) has been consumed for the treatment of insomnia and anxiety in Asia. To provide further scientific basis to traditional uses of this fruit on insomnia, we evaluated the effects of methanol extract of Longanae Arillus (MELA) on the alteration of sleep architecture and electroencephalogram (EEG) power spectra in acutely and chronically restraint-stressed rats. Following postsurgical recovery, Polygraphic signs of sleep-wake activities were recorded for 24 h after MELA administration in rats. Rats in the acute stress and chronic stress were administered with MELA for 10 days. On the $8^{th},\;9^{th}\;and\;10^{th}$ day of MELA administration, the rats were stressed for 3 h once per day. On the $10^{th}$ day and 1 h after MELA administration, the rats were stressed once for 22 h in the chronic stress group. Acute and chronic stress induced alternations in cortex EEG recordings during non-rapid eye movement (NREM), rapid eye movement (REM) sleep and wakefulness. MELA shortened the total and REM sleep and increased the wakefulness in night time recording without changing daytime recordings. Chronic stress increased wakefulness and REM sleep, decreased total and NREM sleep in the daytime recording, and increased REM and decreased NREM sleep without changing total sleep and wakefulness in night time recording. These findings suggest that MELA ameliorated the alterations in REM and NREM sleep of acutely and chronically stressed rats via modulation of cortical ${\alpha}-$, ${\theta}-$ and ${\delta}-$ wave activity.

• Journal of Ginseng Research
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• v.34 no.1
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• pp.30-40
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• 2010

The present investigation was conducted to evaluate the regulation of sleep architecture by the red ginseng water extract (RGE) in acutely and chronically restraint stressed rats. Adult rats were fitted with sleep.wake recording electrodes. Following post-surgical recovery, rats were extensively habituated for freely moving polygraphic recording conditions. Polygraphic signs of sleep-wake activities were recorded for 24 h after RGE administration and induction of stress and were analyzed to understand the regulation of sleep architecture. Acute stress decreased wakefulness and increased total sleep, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep in both the daytime and nighttime recording. RGE shortened the daytime NREM and REM sleep, without changing the wakefulness and total sleep. RGE increased nighttime wakefulness, and decreased total, NREM and REM sleep. Chronic stress increased wakefulness and decreased total sleep in the daytime recording, and increased REM and decreased NREM sleep in both the day and night time recording. RGE ameliorated chronic stress and induced alterations of REM and NREM sleep in the day and night time sleep architecture. Acute and chronic stress could also induce alternations in cortex electroencephalogram (EEG) recording during NREM, REM sleep and wakefulness. These findings suggest that RGE may modulate the sleep behavior in acutely and chronically stressed rats and the ameliorating effect of RGE on the sleep architecture may involve in modulation of $\alpha$-, $\theta$- and $\delta$- wave activities of the cortical EEG.

• Sleep Medicine and Psychophysiology
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• v.11 no.1
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• pp.10-16
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• 2004

Sleep is associated with definite changes in respiratory function in normal human beings. During sleep, there is loss of voluntary control of breathing and a decrease in the usual ventilatory response to both low oxygen and high carbon dioxide levels. Especially, rapid eye movement (REM) sleep is a distinct neurophysiological state associated with significant changes in breathing pattern and ventilatory control as compared with both wakefulness and non-rapid eye movement (NREM) sleep. REM sleep is characterized by erratic, shallow breathing with irregularities both in amplitude and frequency owing to marked reduction in intercostal and upper airway muscle activity. These blunted ventilatory responses during sleep are clinically important. They permit marked hypoxemia that occurs during REM sleep in patients with lung or chest wall disease. In addition, sleep-disordered breathing (SDB) is more frequent and longer and hypoventilation is more pronounced during REM sleep. Although apneic episodes are most frequent and severe during REM sleep, most adults spend less than 20 to 25% of total sleep time in REM sleep. It is, therefore, possible for patients to have frequent apneas and hypopneas during REM sleep and still have a normal apnea-hypopnea index if the event-rich REM periods are diluted by event-poor periods of NREM sleep. In this review, we address respiratory physiology according to sleep stage, and the clinical implications of SDB and hypoventilation aggravated during REM sleep.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.586-592
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• 2017

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via ${\gamma}$-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through $GABA_A$-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

• Natural Product Sciences
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• v.21 no.3
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• pp.219-225
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• 2015

In the previous experiments, we reported that ethanol extract of Gastrodiae Rhizoma, the dried tuber of Gastrodia ElataBlume (Orchidaceae) increased pentobarbital-induced sleeping behaviors. These experiments were undertaken to know whether 4-hydroxybenzaldehyde (4-HBD), is one of the major compounds of Gastrodiae Rhizoma increases pentobarbital-induced sleeping behaviors and changes sleep architectures via activating GABA_A-ergic systems in rodents. 4-HBD decreased locomotor activity in mice. 4-HBD increased total sleep time, and decreased of sleep onset by pentobarbital (28 mg/kg and 40 mg/kg). 4-HBD showed synergistic effects with muscimol (a GABA_A receptor agonist), shortening sleep onset and enhancing sleep time on pentobarbital-induced sleeping behaviors. On the other hand, 4-HBD (200 mg/kg, p.o.) itself significantly inhibited the counts of sleepwake cycles, and prolonged total sleep time and non-rapid eye movement (NREM) in rats. Moreover, 4-HBD increased intracellular Cl⁻ levels in the primary cultured cerebellar cells. The protein levels of glutamic acid decarboxylase (GAD) and GABA_A receptors subunits were over-expressed by 4-HBD. Consequently, these results demonstrate that 4-HBD increased NREM sleep as well as sleeping behaviors via the activation of GABA_A-ergic systems in rodents.

• Clinical and Experimental Pediatrics
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• v.50 no.8
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• pp.711-717
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• 2007

Sleep is a vital, highly organized process regulated by complex systems of neuronal networks and neurotransmitters. Normal sleep comprises non-rapid eye movement (NREM) and REM periods that alternate through the night. Sleep usually begins in NREM and progresses through deeper NREM stages (2, 3, and 4 stages), but newborns enter REM sleep (active sleep) first before NREM (quiet sleep). A period of NREM and REM sleep cycle is approximately 90 minutes, but newborn have a shorter sleep cycle (50 minutes). As children mature, sleep changes as an adult pattern: shorter sleep duration, longer sleep cycles and less daytime sleep. REM sleep is approximately 50% of total sleep in newborn and dramatically decreases over the first 2 years into adulthood (20% to 25%). An initial predominant of slow wave sleep (stage 3 and 4) that peaks in early childhood, drops off abruptly after adolescence by 40% from preteen years, and then declines over the life span. The hypothalamus is recognized as a key area of brain involved in regulation of sleep and wakefulness. The basic function of sleep largely remains elusive, but it is clear that sleep plays an important role in the regulation of CNS and body physiologic processes. Understanding of the architecture of sleep and basic mechanisms that regulate sleep and wake cycle are essential to evaluate normal or abnormal development of sleep pattern changes with age. Reduction or disruption of sleep can have a significant impact on daytime functioning and development, including learning, growth, behavior, and emotional regulation.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.219-225
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• 2010

We tested whether ginsenosides $Rg_3$-standardized ginseng extract (RGE) has anti-stress effects in restraint-stressed animals. RGE increased time spent in the open arms and open arm entries in the elevated plus-maze test. In addition, RGE blocked the reduction of center zone distance and stereotypes behaviors in the open-field test. RGE also increased head dips in stressed mice, indicating anxiolytic-like effects. Stress decreased movement distance and duration, burrowing, and rearing frequency but increased face washing and grooming. RGE significantly reversed burrowing and rearing activity in stressed mice. In addition, we measured sleep architecture in restraint stressed rats using EEG recorder. Stress increased rapid eye movement (REM) sleep, but total sleep and non-rapid eye movement (NREM) sleep were not changed. RGE did not affect sleep architecture in stressed rats. These behavioral experiments suggest that RGE has anti-stress effects in restraint-stressed animal models.

• Proceedings of the Korean Society for Emotion and Sensibility Conference
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• 2009.05a
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• pp.209-210
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• 2009

수면단계는 수면감성을 평가하는데 있어서 중요한 생리지표로서 사용되어왔다. 그러나 수면다원검사를 이용한 전통적 수면단계 분류방법은 뇌전도, 안전도, 심전도, 근전도 등을 종합적으로 측정하므로 수면단계를 비교적 정확히 분류할 수 있지만 피험자에게 심한 구속감을 주는 문제가 있다. 본 연구에서는, 각성상태에서 교감신경계가 지배적인 반면에 수면 중에는 부교감신경계가 더 활동적인 점에 착안하여 수면단계를 간단히 분류할 수 있는 방법을 찾고자 수면단계에 따른 심박동변이도(heart rate variability: HRV)를 분석하였다. 단일채널 심전도를 이용하여 수면단계별로 HRV 의 교감신경계/부교감신경계 활성도의 비율을 분석한 결과, W(wakefulness) 단계가 NREN(non REM) 2 단계, 3 단계, 4 단계에 비하여 높게 나타났으며, NREM 4 단계는 REM(rapid eye movement) 단계와 NREM 1단계에 비하여 낮게 나타났다. 또한 교감신경계/부교감신경계 활성도 비율의 수면단계에 따라 변화하는 양상은 W, REM, NREM 1, 2, 3, 4 단계의 순으로 단조 감소하였다.