Neuroscience Letters, 111 (1990) 217-221
217
Elsevier Scientific Publishers Ireland Ltd. NSL 06753
Chronic intake of Panax ginseng extract stabilizes sleep and wakefulness in food-deprived rats S u n g Pil Lee l, K a z u k i H o n d a l, Y o u n g H o R h e e 2 a n d S h o j i r o I n o u 6 l 1Institutefor Medical and Dental Engineering, Tokyo Medical and Dental University, Tokyo (Japan) and 2Department of Neuropsychiatry, College of Medicine, Chungbuk National University, Chungju (Korea)
(Received 2 November 1989; Revisedversion received 1 December 1989; Accepted 1 December 1989) Key words: Food deprivation; Ginseng extract; Rat; Slow wave sleep; Wakefulness
The amount of wakefulness and slow wave sleep significantly fluctuated during 48 h food deprivation and subsequent recoveryperiods in freely behaving male rats. In contrast, such fluctuations were significantly less prominent in age-matchedmale rats chronicallytreated with Panax ginseng extract via drinking water. It is speculated that the ginseng extract may exert a stabilizing effect on sleep-wakingdisturbances which possiblyaccounts for its outstanding health-improvingactivities.
The ginseng, P a n a x ginseng, as a herbal medicine is well known for its outstanding effect on the improvement of h u m a n health in general (for reviews, see refs. 9, 14, 24). The ginseng root contains a number of physiologically important constituents [8]. In rats, it is reported that ginseng extract exerts a decrease in blood pressure [19, 21], a suppression of conditioned avoidance response [17, 19, 20, 22] and sound discrimination [20], an inhibition of gastric ulceration [2], a facilitation of sexual behavior [15], and an increase in essential fatty acids [11] and several essential amino acids [12] in serum. On the assumption that the health-improving effect of the ginseng might be, at least in part, related to the maintenance of a normal state of sleep and wakefulness, we have detected an electroencephalographic (EEG) sleep-modulatory effect of P a n a x ginseng extract in adult freely behaving rats [13, 18]. Using the same approach methods, the present study was conducted to evidence a state-modulatory effect of the ginseng on animals raised under a ginseng treatment. Pregnant female rats of the Sprague-Dawley strain, kept on a 12-h light and 12-h dark schedule (lights on: 08.00-20.00 h) under a constant air-conditioned environment o f 25 4- 1°C and 60 4- 6 % relative humidity with free access to rat chow, were
Correspondence: S. Inou6, Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Kanda-Surugadai 2-3-10, Chiyoda-ku, Tokyo 101, Japan.
0304-3940/90/$ 03.50 © 1990 ElsevierScientific Publishers Ireland Ltd.
218 individually isolated at 17 to 20 days of gestation for delivery and lactation. They were divided into a control group and an experimental group; the former and the latter were given tap water and ginseng water ad libitum, respectively. The ginseng water contained 0.5 mg per ml of Panax ginseng extract (Korean Red Ginseng Extract, Korea Monopoly Corporation). On the 2nd day of delivery, the litter size was adjusted to 8 pups per mother. On 21 days of age, pups of each group were weaned; 4-5 males were housed in a cage where one of the two kinds of water was given as before. At the age of 60-70 days, the males weighing 300-400 g were anesthetized with pentobarbital sodium and implanted with 3 cortical EEG electrodes and 2 nuchal electromyographic (EMG) electrodes according to the technique described in a previous paper [5]. The animals were individually housed in a special cage which enabled continuous monitoring of EEG and EMG. Lead wires of the electrodes were connected with a polygraph (Nihon-Kohden EEG-4317) via a slip ring fixed above the cage. Thus free movement of the rats was guaranteed. Tap water for the control rats and the ginseng water for the experimental rats were given as before. Each cage was placed in a sound-proof, electromagnetically shielded chamber under the same environmental conditions as above. One week was allowed to recover from the surgery. After observing the establishment of circadian rhythms in sleep-waking behavior, the rats of both groups were subjected to experiments for 4 days starting at the onset of the light period. Following 24 h baseline recording on day 1, rat chow was taken away from the cage for 48 h (days 2 3) and returned on day 4. Throughout the period, tap water for the control rats and the ginseng water for the experimental rats were given as before. The daily dose of the ginseng extract around this period was ca. 15 mg, since the daily intake of drinking water was 31 ml in our young adult male rats [7]. This dosage is comparable to that recommended for human use (3 g for a person weighing 60-80 kg). During the 4-day sessions, EEG (bipolarly registered between 2 combinations of the 3 electrodes) and E M G were polygraphically recorded at a paper speed of 0.5 mm/s. Sleep-waking states were visually classified on a large scale digitizer as slow wave sleep (SWS), paradoxical sleep (PS) and wakefulness (W) according to our routinized criteria, numerically stored and processed in a computer system [6]. Intra- and intergroup differences in the data of days 1 4 were statistically analyzed by Student's t-test. There was no difference in the baseline quantity of SWS and W between the control and the ginseng-treated rats except for the amount of diurnal PS (Fig. 1). Food deprivation initially caused an increase in SWS and a decrease in W in both groups during the light and the dark period of day 2. However, the changes were significant only in the control group as compared to the baseline value of day 1 (P
217
Elsevier Scientific Publishers Ireland Ltd. NSL 06753
Chronic intake of Panax ginseng extract stabilizes sleep and wakefulness in food-deprived rats S u n g Pil Lee l, K a z u k i H o n d a l, Y o u n g H o R h e e 2 a n d S h o j i r o I n o u 6 l 1Institutefor Medical and Dental Engineering, Tokyo Medical and Dental University, Tokyo (Japan) and 2Department of Neuropsychiatry, College of Medicine, Chungbuk National University, Chungju (Korea)
(Received 2 November 1989; Revisedversion received 1 December 1989; Accepted 1 December 1989) Key words: Food deprivation; Ginseng extract; Rat; Slow wave sleep; Wakefulness
The amount of wakefulness and slow wave sleep significantly fluctuated during 48 h food deprivation and subsequent recoveryperiods in freely behaving male rats. In contrast, such fluctuations were significantly less prominent in age-matchedmale rats chronicallytreated with Panax ginseng extract via drinking water. It is speculated that the ginseng extract may exert a stabilizing effect on sleep-wakingdisturbances which possiblyaccounts for its outstanding health-improvingactivities.
The ginseng, P a n a x ginseng, as a herbal medicine is well known for its outstanding effect on the improvement of h u m a n health in general (for reviews, see refs. 9, 14, 24). The ginseng root contains a number of physiologically important constituents [8]. In rats, it is reported that ginseng extract exerts a decrease in blood pressure [19, 21], a suppression of conditioned avoidance response [17, 19, 20, 22] and sound discrimination [20], an inhibition of gastric ulceration [2], a facilitation of sexual behavior [15], and an increase in essential fatty acids [11] and several essential amino acids [12] in serum. On the assumption that the health-improving effect of the ginseng might be, at least in part, related to the maintenance of a normal state of sleep and wakefulness, we have detected an electroencephalographic (EEG) sleep-modulatory effect of P a n a x ginseng extract in adult freely behaving rats [13, 18]. Using the same approach methods, the present study was conducted to evidence a state-modulatory effect of the ginseng on animals raised under a ginseng treatment. Pregnant female rats of the Sprague-Dawley strain, kept on a 12-h light and 12-h dark schedule (lights on: 08.00-20.00 h) under a constant air-conditioned environment o f 25 4- 1°C and 60 4- 6 % relative humidity with free access to rat chow, were
Correspondence: S. Inou6, Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Kanda-Surugadai 2-3-10, Chiyoda-ku, Tokyo 101, Japan.
0304-3940/90/$ 03.50 © 1990 ElsevierScientific Publishers Ireland Ltd.
218 individually isolated at 17 to 20 days of gestation for delivery and lactation. They were divided into a control group and an experimental group; the former and the latter were given tap water and ginseng water ad libitum, respectively. The ginseng water contained 0.5 mg per ml of Panax ginseng extract (Korean Red Ginseng Extract, Korea Monopoly Corporation). On the 2nd day of delivery, the litter size was adjusted to 8 pups per mother. On 21 days of age, pups of each group were weaned; 4-5 males were housed in a cage where one of the two kinds of water was given as before. At the age of 60-70 days, the males weighing 300-400 g were anesthetized with pentobarbital sodium and implanted with 3 cortical EEG electrodes and 2 nuchal electromyographic (EMG) electrodes according to the technique described in a previous paper [5]. The animals were individually housed in a special cage which enabled continuous monitoring of EEG and EMG. Lead wires of the electrodes were connected with a polygraph (Nihon-Kohden EEG-4317) via a slip ring fixed above the cage. Thus free movement of the rats was guaranteed. Tap water for the control rats and the ginseng water for the experimental rats were given as before. Each cage was placed in a sound-proof, electromagnetically shielded chamber under the same environmental conditions as above. One week was allowed to recover from the surgery. After observing the establishment of circadian rhythms in sleep-waking behavior, the rats of both groups were subjected to experiments for 4 days starting at the onset of the light period. Following 24 h baseline recording on day 1, rat chow was taken away from the cage for 48 h (days 2 3) and returned on day 4. Throughout the period, tap water for the control rats and the ginseng water for the experimental rats were given as before. The daily dose of the ginseng extract around this period was ca. 15 mg, since the daily intake of drinking water was 31 ml in our young adult male rats [7]. This dosage is comparable to that recommended for human use (3 g for a person weighing 60-80 kg). During the 4-day sessions, EEG (bipolarly registered between 2 combinations of the 3 electrodes) and E M G were polygraphically recorded at a paper speed of 0.5 mm/s. Sleep-waking states were visually classified on a large scale digitizer as slow wave sleep (SWS), paradoxical sleep (PS) and wakefulness (W) according to our routinized criteria, numerically stored and processed in a computer system [6]. Intra- and intergroup differences in the data of days 1 4 were statistically analyzed by Student's t-test. There was no difference in the baseline quantity of SWS and W between the control and the ginseng-treated rats except for the amount of diurnal PS (Fig. 1). Food deprivation initially caused an increase in SWS and a decrease in W in both groups during the light and the dark period of day 2. However, the changes were significant only in the control group as compared to the baseline value of day 1 (P
