“…Higher levels of deep sleep require stronger stimuli to switch to wakefulness. NREM sleep starts with the N1 or N2 stages, which have a relatively low depth, and further progresses to the N3 stage (slow-wave sleep), characterized by high-amplitude δ waves A decrease in the slow-wave ratio has been reported in insomnia [29], and an increase in this wave improves sleep disorders and affects sleep quality [29]. An increase in sleep time by ZW-FM as seen by an increased NREM can be attributed to an increase in δ waves (Figure 5).…”
Although Ziziphus jujuba Mill (jujube) is used in folk medicine for hypnotic sedative, anxiolytic, and many other purposes, to date, only a few studies have revealed its sleep-promoting effects and related mechanisms. Currently, drugs used for the treatment of sleep disorders have various side effects, so it is essential to develop safe natural materials. Therefore, we evaluated the sleep-enhancing activity and mechanism of action of an aqueous extract of jujube seeds (ZW) fermented with Lactobacillus brevis L-32 in rodent models. The starch contained in ZW was removed by enzymatic degradation and fermented with L. brevis to obtain a fermented product (ZW-FM) with a high γ-aminobutyric acid (GABA) content. To evaluate the sleep-promoting effect of ZW-FM, pentobarbital-induced sleep tests were performed on ICR mice, and electroencephalography analysis was undertaken in Sprague Dawley rats. Additionally, the awakening relief effects of ZW-FM were confirmed in a caffeine-induced insomnia model. Finally, the mechanism of sleep enhancement by ZW-FM was analyzed using GABA receptor type A (GABAA) antagonists. The ZW-FM-treated groups (100 and 150 mg/kg) showed increased sleep time, especially the δ-wave time during non-rapid eye movement (NREM) sleep. In addition, the 150 mg/kg ZW-FM treatment group showed decreased sleep latency and increased sleep time in the insomnia model. In particular, NREM sleep time was increased and REM sleep time, which was increased by caffeine treatment, was decreased by ZW-FM treatment. ZW-FM-induced sleep increase was inhibited by the GABAA receptor antagonists picrotoxin, bicuculline, and flumazenil, confirming that the increase was the result of a GABAergic mechanism. These results strongly suggest that the increased GABA in water extract from jujube seeds fermented by L. brevis acts as a sleep-promoting compound and that the sleep-promoting activity is related to GABAA receptor binding.
“…Higher levels of deep sleep require stronger stimuli to switch to wakefulness. NREM sleep starts with the N1 or N2 stages, which have a relatively low depth, and further progresses to the N3 stage (slow-wave sleep), characterized by high-amplitude δ waves A decrease in the slow-wave ratio has been reported in insomnia [29], and an increase in this wave improves sleep disorders and affects sleep quality [29]. An increase in sleep time by ZW-FM as seen by an increased NREM can be attributed to an increase in δ waves (Figure 5).…”
Although Ziziphus jujuba Mill (jujube) is used in folk medicine for hypnotic sedative, anxiolytic, and many other purposes, to date, only a few studies have revealed its sleep-promoting effects and related mechanisms. Currently, drugs used for the treatment of sleep disorders have various side effects, so it is essential to develop safe natural materials. Therefore, we evaluated the sleep-enhancing activity and mechanism of action of an aqueous extract of jujube seeds (ZW) fermented with Lactobacillus brevis L-32 in rodent models. The starch contained in ZW was removed by enzymatic degradation and fermented with L. brevis to obtain a fermented product (ZW-FM) with a high γ-aminobutyric acid (GABA) content. To evaluate the sleep-promoting effect of ZW-FM, pentobarbital-induced sleep tests were performed on ICR mice, and electroencephalography analysis was undertaken in Sprague Dawley rats. Additionally, the awakening relief effects of ZW-FM were confirmed in a caffeine-induced insomnia model. Finally, the mechanism of sleep enhancement by ZW-FM was analyzed using GABA receptor type A (GABAA) antagonists. The ZW-FM-treated groups (100 and 150 mg/kg) showed increased sleep time, especially the δ-wave time during non-rapid eye movement (NREM) sleep. In addition, the 150 mg/kg ZW-FM treatment group showed decreased sleep latency and increased sleep time in the insomnia model. In particular, NREM sleep time was increased and REM sleep time, which was increased by caffeine treatment, was decreased by ZW-FM treatment. ZW-FM-induced sleep increase was inhibited by the GABAA receptor antagonists picrotoxin, bicuculline, and flumazenil, confirming that the increase was the result of a GABAergic mechanism. These results strongly suggest that the increased GABA in water extract from jujube seeds fermented by L. brevis acts as a sleep-promoting compound and that the sleep-promoting activity is related to GABAA receptor binding.
“…Thank you for allowing me to respond to a Letter to the Editor concerning my recent publication in Sleep Medicine X [ 1 ]. The authors have presented both unpublished data from a publication of their own [ 2 ] as well as from Lopez et al.…”
“…We read with great interest the review entitled "Disorders of Arousal and timing of the first period of slow wave sleep: Clinical and forensic implications" by M. R. Pressman [ 1 ]. The author found that the mean slow wave sleep latency (SWSL) could be as short as 10.6 min in normal subjects (and even shorter if sleep deprivation and alcohol consumption were combined), in contrast to the 30–120 min range used by some experts to determine whether a criminal case may be related to a disorder of arousal (DOA).…”
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