Trends in Research on Patients With COVID-19 in Korean Medical Journals.

OBJECTIVES: This study was conducted to systematically summarize trends in research concerning patients with coronavirus disease 2019 (COVID-19) as reported in Korean medical journals. METHODS: We performed a literature search of KoreaMed from January 2020 to September 2022. We included only primary studies of patients with COVID-19. Two reviewers screened titles and abstracts, then performed full-text screening, both independently and in duplicate. We first identified the 5 journals with the greatest numbers of eligible publications, then extracted data pertaining to the general characteristics, study population attributes, and research features of papers published in these journals. RESULTS: Our analysis encompassed 142 primary studies. Of these, approximately 41.0% reported a funding source, while 3.5% disclosed a conflict of interest. In 2020, 42.9% of studies included fewer than 10 participants; however, by 2022, the proportion of studies with over 200 participants had increased to 40.6%. The most common design was the cohort study (48.6%), followed by case reports/series (35.2%). Only 3 randomized controlled trials were identified. Studies most frequently focused on prognosis (58.5%), followed by therapy/intervention (20.4%). Regarding the type of intervention/exposure, therapeutic clinical interventions comprised 26.1%, while studies of morbidity accounted for 13.4%. As for the outcomes measured, 50.7% of studies assessed symptoms/clinical status/improvement, and 14.1% evaluated mortality. CONCLUSIONS: Employing a systematic approach, we examined the characteristics of research involving patients with COVID-19 that was published in Korean medical journals from 2020 onward. Subsequent research should assess not only publication trends over a longer timeframe but also the quality of evidence provided.

γ-Oryzanol Ameliorates Depressive Behavior in Ovariectomized Mice by Regulating Hippocampal Nitric Oxide Synthase: A Potential Therapy for Menopausal Depression.

SCOPE: Depression is a severe mental condition, common among menopausal women. γ-Oryzanol (ORY) has various biological properties; however, the effect of ORY on menopausal depression and its underlying mechanisms have not been investigated. METHODS AND RESULTS: ORY is orally administered to ovariectomized (OVX) mice for 20 weeks. ORY administration results in lower immobility time in the tail suspension and forced swim test and increases locomotor activity in the open field test. In the primary hippocampal neurons and hippocampi of OVX mice, ORY treatment increases nitric oxide (NO) production and neuronal NO synthase (nNOS) expression. Further, the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and tropomyosin receptor kinase B, along with the expression of brain-derived neurotrophic factior (BDNF), is upregulated. These stimulatory effects of ORY are diminished by treatment with estrogen receptor ß (ERß) antagonist. ORY similarly interacts with ERß in the molecular docking analysis. Moreover, intracerebroventricular injection of 7-nitroindazole, a nNOS inhibitor, abolishes the antidepressant effects of ORY. CONCLUSIONS: The results indicate that ORY attenuates depressive behavior in OVX mice by upregulating ERß-mediated hippocampal nNOS expression and activating the ERK-CREB-BDNF signaling networks. The findings suggest that ORY is a potential therapeutic agent for attenuating menopausal depression.

Aralia continentalis Root Enhances Non-Rapid Eye Movement Sleep by Activating GABAA Receptors.

Aralia continentalis exhibits various biological activities; however, their sleep-promoting effects have not been previously reported. In this study, we evaluated the hypnotic effects and sleep-wake profiles of A. continentalis root (KS-126) using a pentobarbital-induced sleep-acceleration test and polysomnographic recordings. Additionally, we investigated the molecular mechanism of KS-126 through patch-clamp electrophysiology. Our polysomnographic recordings revealed that KS-126 not only accelerated the onset of non-rapid eye movement sleep (NREMS) but also extends its duration. Considering the temporal dynamics of the sleep-wake stages, during the initial and subsequent periods KS-126 extended NREMS duration and decreased wakefulness, thereby enhancing sleep-promoting effects. Furthermore, the assessment of sleep quality via analysis of electroencephalogram power density indicated that KS-126 did not significantly alter sleep intensity. Finally, we found that KS-126 enhanced GABAA receptor-mediated synaptic responses in primary hippocampal neurons, leading to an increase in the percentage of the GABA current. This effect was not affected by the selective benzodiazepine receptor antagonist flumazenil, but was entirely inhibited by the GABAA receptor antagonist bicuculline. In conclusion, KS-126 extends the duration of NREMS without altering its intensity by prolonging GABAergic synaptic transmission, which modulates GABAA receptor function.

Effects of Chronic Administration of Green Tea Ethanol Extract on Sleep Architecture in Mice: A Comparative Study with a Representative Stimulant Caffeine.

Wakefulness is defined as a state in which individuals can react to a change in situations. The number of people staying awake and compensating for lack of sleep has increased in recent years. Caffeine, a representative stimulant, is the most extensively consumed compound globally and is mainly consumed through coffee. Although green tea (Camellia sinensis L.) contains high caffeine content like coffee, its arousal-inducing effects have not yet been studied. In the present study, we aimed to identify the arousal-inducing effect of GT during a chronic administration period (three weeks) using analysis of sleep architecture. Treatment with GT (1500 mg/kg) significantly elevated the sleep latency and wakefulness throughout the treatment period, and chronic administration of GT consistently maintained an increase in wakefulness for up to 3 h. During the treatment period, the arousal-inducing effect of GT (1500 mg/kg) occurred without any change in the tolerance phenomenon or withdrawal symptoms, similar to that observed with caffeine (25 mg/kg). GT (1500 mg/kg) containing 95.6 mg/kg of caffeine did not produce a better arousal-inducing effect than caffeine at 25 mg/kg. These results indicate that the arousal-inducing effect of GT persisted for three weeks without adverse effects and that GT can control the arousal-inducing effects of caffeine due to the hypnotic effects of its other constituents.

Correction: Curcuminoids, a major turmeric component, have a sleep-enhancing effect by targeting the histamine H1 receptor.

Correction for 'Curcuminoids, a major turmeric component, have a sleep-enhancing effect by targeting the histamine H1 receptor' by Min Young Um et al., Food Funct., 2022, 13, 12697-12706, https://doi.org/10.1039/D2FO02087D.

Marine Polyphenol Phlorotannins as a Natural Sleep Aid for Treatment of Insomnia: A Review of Sedative-Hypnotic Effects and Mechanism of Action.

Insomnia is a common sleep disorder. Natural sleep aids are gaining worldwide popularity as alternatives to prescription drugs for improving sleep. Recently, numerous studies have investigated the sedative-hypnotic effects of the polyphenols of terrestrial plants. The hypnotic effects of marine polyphenols have also been studied in recent years. Phlorotannins are marine polyphenols that are found only in brown algae. Phlorotannins exert sedative-hypnotic effects via the gamma-aminobutyric acid type A-benzodiazepine receptor. In addition, the brown seaweed Ecklonia cava supplement containing phlorotannins has been approved by the Ministry of Food and Drug Safety as a health-functional ingredient that helps improve sleep quality. Currently, it is meaningful to deal with the sedative-hypnotic effects of phlorotannins as natural sleep aids. The current review comprehensively presents the sedative-hypnotic effects in animal models and human clinical trials as well as their mechanism of action, extraction, purification, and safety.

Effects of Green Kiwifruit Peel Extract on Sleep-Wake Profiles in Mice: A Polysomnographic Study Based on Electroencephalogram and Electromyogram Recordings.

In the previous study, it was reported that green kiwifruit peel ethanol extract (GKPEE) increases sleep duration and decreases sleep latency in pentobarbital-treated mice. The pentobarbital-induced sleep test can be used to verify sleep quantity, which includes factors such as sleep duration and latency, but not sleep quality. In the present study, the sleep-promoting effects of GKPEE were investigated by the analysis of electroencephalogram (EEG) and electromyogram in mice and were compared with the results of diazepam (DZP), a representative sedative-hypnotic agent. The acute administration of GKPEE (250, 500 and 1000 mg/kg) increased the amount of non-rapid eye movement sleep (NREMS) and decreased sleep latency in a dose-dependent manner. The effect of GKPEE at 1000 mg/kg produced persistently significantly different results until the second hour of time-course changes. In particular, GKPEE did not produce any change in delta activity compared to DZP. Furthermore, sub-chronic administration (15 days) of GKPEE (500 mg/kg) continued sleep-promoting effects, whilst the EEG power density of NREMS did not show significant differences, indicating that there were no tolerance phenomena. Our findings suggest that GKPEE may be a promising natural sleep aid for treating sleep disorders. In addition, considering the number of by-products discarded each year by the food industry, the application of GKPEE here contributes to the utilization of processed kiwifruit by-products and can help to solve environmental problems.

Curcuminoids, a major turmeric component, have a sleep-enhancing effect by targeting the histamine H1 receptor.

Turmeric (Curcuma longa) had been considered as a universal panacea in functional foods and traditional medicines. In recent, the sedative-hypnotic effect of turmeric extract (TE) was reported. However, sleep-promoting compounds in TE have been not yet demonstrated. Curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) are the major constituents of turmeric being responsible for its various biological activities. Therefore, they can be first assumed to be sedative-hypnotic compounds of TE. In the present study, we aimed to investigate the effects and underlying mechanisms of curcuminoids and each constituent on the sleep-wake cycle of mice. Molecular docking studies, histamine H1 receptor (H1R) binding assays, and H1R knockout animal studies were used to investigate the molecular mechanisms underlying the sleep-promoting effects. Curcuminoids and their constituents reduced sleep latency and increased sleep duration in the pentobarbital-induced sleep test in mice. In addition, curcuminoids significantly increased the duration of NREMS and reduced sleep latency without altering the REMS and delta activity. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin were predicted to interact with H1R in the molecular model. In the binding affinity assay, we found that curcuminoids, as well as their constituents, significantly bind to H1R with the Ki value of 1.49 µg mL-1. Furthermore, sleep latency was reduced and NREMS frequency was increased following curcuminoid administration in wild-type mice but not in H1R knockout mice. Therefore, we conclude that curcuminoids reduce sleep latency and enhance the quantity of NREMS by acting as modulators of H1R, indicating their usefulness in treating insomnia.

Frame-rate up-conversion detection based on convolutional neural network for learning spatiotemporal features.

With the advance in user-friendly and powerful video editing tools, anyone can easily manipulate videos without leaving prominent visual traces. Frame-rate up-conversion (FRUC), a representative temporal-domain operation, increases the motion continuity of videos with a lower frame-rate and is used by malicious counterfeiters in video tampering such as generating fake frame-rate video without improving the quality or mixing temporally spliced videos. FRUC is based on frame interpolation schemes and subtle artifacts that remain in interpolated frames are often difficult to distinguish. Hence, detecting such forgery traces is a critical issue in video forensics. This paper proposes a frame-rate conversion detection network (FCDNet) that learns forensic features caused by FRUC in an end-to-end fashion. The proposed network uses a stack of consecutive frames as the input and effectively learns interpolation artifacts using network blocks to learn spatiotemporal features. Moreover, it can cover the following three types of frame interpolation schemes: nearest neighbor interpolation, bilinear interpolation, and motion-compensated interpolation. In contrast to existing methods that exploit all frames to verify integrity, the proposed approach achieves a high detection speed because it observes only six frames to test its authenticity. Extensive experiments were conducted with conventional forensic methods and neural networks for video forensics to validate our research. The proposed work achieved an outstanding performance in terms of detecting the interpolated artifacts of FRUC. The experimental results also demonstrate that our model is robust against an unseen dataset, unlearned frame-rate, and unlearned quality factor. Furthermore, FCDNet can precisely localize the tampered region applied to manipulation along the time-domain through temporal localization.

Effect of Black Pepper (Piper nigrum) Extract on Caffeine-Induced Sleep Disruption and Excitation in Mice.

Sleep is one of the most essential factors required to maintain good health. However, the global prevalence of insomnia is increasing, and caffeine intake is a major trigger. The objective of this study was to investigate the inhibitory effect of black pepper, Piper nigrum extract (PE), on caffeine-induced sleep disruption and excitation in mice. Caffeine significantly decreased sleep duration in the pentobarbital-induced sleep test. It also resulted in a significant increase in sleep onset and a decrease in non-rapid eye movement sleep. Moreover, in an open-field test, caffeine-treated mice exhibited a significantly increased time in the center zone and total distance traveled. However, the co-administration of caffeine and PE did not result in similar arousal activities. Thus, our results suggest that PE can be used as a potential therapeutic agent to treat sleep problems and excitatory status associated with caffeine intake.

1,3-Dicaffeoylquinic Acid as an Active Compound of Arctium lappa Root Extract Ameliorates Depressive-Like Behavior by Regulating Hippocampal Nitric Oxide Synthesis in Ovariectomized Mice.

Menopause is a risk factor for depression. Although 1,3-dicaffeoylquinic acid (1,3-diCQA), a phenolic compound in Arctium lappa (A. lappa) root, has various health benefits, its effects on menopausal depression remain to be determined. Therefore, this study investigates the antidepressant-like effects of 1,3-diCQA from an A. lappa root extract (AE) and the associated molecular mechanisms. Ovariectomized (OVX) mice were orally administered AE for 20 weeks, following which depression-like behaviors were assessed. Although the mice exhibited depression-like behaviors, AE administration mitigated these symptoms by activating the ERK-CREB-BDNF pathway and increasing nNOS levels in the hippocampus. Similarly, a significant increase in nNOS-derived NO production and activation of the ERK-CREB-BDNF pathway was observed in the primary hippocampal neurons. Although this stimulatory effect of 1,3-diCQA was not significantly affected by treatment with estrogen receptor agonist or antagonist, it was inhibited by 7-NI, an nNOS inhibitor. Moreover, mice treated with 1,3-diCQA exhibited a marked improvement in their forced swimming test and tail suspension test immobility, while pretreatment with 7-NI reversed the antidepressant-like effects of 1,3-diCQA. Our results suggest that 1,3-diCQA regulates nNOS in an estrogen recepters-independent manner to increase NO production in OVX mice.

Arousal-Inducing Effect of Garcinia cambogia Peel Extract in Pentobarbital-Induced Sleep Test and Electroencephalographic Analysis.

Caffeine, a natural stimulant, is known to be effective for weight loss. On this basis, we screened the arousal-inducing effect of five dietary supplements with a weight loss effect (Garcinia cambogia, Coleus forskohlii, Camellia sinensis L., Irvingia gabonensis, and Malus pumila M.), of which the G. cambogia peel extract (GC) showed a significant arousal-inducing effect in the pentobarbital-induced sleep test in mice. This characteristic of GC was further evaluated by analysis of electroencephalogram and electromyogram in C57L/6N mice, and it was compared to that of the positive control, caffeine. Administration of GC (1500 mg/kg) significantly increased wakefulness and decreased non-rapid eye movement sleep, similar to that of caffeine (25 mg/kg), with GC and caffeine showing a significant increase in wakefulness at 2 and 6 h, respectively. Compared to that of caffeine, the shorter duration of efficacy of GC could be advantageous because of the lower possibility of sleep disturbance. Furthermore, the arousal-inducing effects of GC (1500 mg/kg) and caffeine (25 mg/kg) persisted throughout the chronic (3 weeks) administration study. This study, for the first time, revealed the arousal-inducing effect of GC. Our findings suggest that GC might be a promising natural stimulant with no side effects. In addition, it is preferential to take GC as a dietary supplement for weight loss during the daytime to avoid sleep disturbances owing to its arousal-inducing effect.

A Novel Potent Sleep-Promoting Effect of Turmeric: Turmeric Increases Non-Rapid Eye Movement Sleep in Mice Via Histamine H1Receptor Blockade.

SCOPE: Turmeric has a broad spectrum of biological properties; however, the sleep-promoting effects of turmeric have not yet been reported. Thus, this study aims to investigate the effect of turmeric on sleep and the molecular mechanism underlying this effect. METHODS AND RESULTS: Pentobarbital-induce sleep test and sleep-wake profile assessment using recorded electroencephalography are used to evaluate the hypnotic effects of the turmeric extract (TE) compared to diazepam on sleep in mice. Additionally, the molecular mechanism of TE's sleep effect is investigated using ex vivo electrophysiological recordings from brain slices in histamine H1 receptor (H1 R) knockout mice. Oral administration of TE and diazepam significantly reduce sleep latency and increase non-rapid eye movement sleep (NREMS) duration without delta activity in mice. Like doxepin, TE inhibits the H1 R agonist (2-pyridylethylamine dihydrochloride)-induced increase in action potentials in the hypothalamic neurons. In animal tests using neurotransmitter agonists or antagonists, TE effect mimick H1 R antagonistic effect of doxepin. Additionally, both reduce sleep latency and increase NREMS in wild-type mice, although these effects are not observed in H1 R knockout mice. CONCLUSION: TE has a sleep-promoting effect owing to reduction in sleep latency and enhancement of NREMS via H1 R blockade; therefore, it could be useful in insomnia.

Standardized rice bran extract improves hepatic steatosis in HepG2 cells and ovariectomized rats.

BACKGROUD/OBJECTIVES: Hepatic steatosis is the most common liver disorder, particularly in postmenopausal women. This study investigated the protective effects of standardized rice bran extract (RBS) on ovariectomized (OVX)-induced hepatic steatosis in rats. MATERIALS/METHODS: HepG2 cells were incubated with 200 µM oleic acid to induce lipid accumulation with or without RBS and γ-oryzanol. OVX rats were separated into three groups and fed a normal diet (ND) or the ND containing 17ß-estradiol (E2; 10 µg/kg) and RBS (500 mg/kg) for 16 weeks. RESULTS: RBS supplementation improved serum triglyceride and free fatty acid levels in OVX rats. Histological analysis showed that RBS significantly attenuated hepatic fat accumulation and decreased hepatic lipid, total cholesterol, and triglyceride levels. Additionally, RBS suppressed the estrogen deficiency-induced upregulation of lipogenic genes, such as sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1, fatty acid synthase, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase 1. CONCLUSIONS: RBS and γ-oryzanol effectively reduced lipid accumulation in a HepG2 cell hepatic steatosis model. RBS improves OVX-induced hepatic steatosis by regulating the SREBP1-mediated activation of lipogenic genes, suggesting the benefits of RBS in preventing fatty liver in postmenopausal women.

Dicaffeoylquinic acids alleviate memory loss via reduction of oxidative stress in stress-hormone-induced depressive mice.

Chronic stress can lead to depression due to elevated levels of stress hormones such as glucocorticoid. This is accompanied by an increase in reactive oxygen species (ROS) levels in the brain, which can cause dendritic spine loss and atrophy in neurons, followed by memory loss. Dicaffeoylquinic acids (diCQAs) are naturally occurring polyphenolic antioxidant compounds in Arctium lappa extracts (AL). The effects of natural derivatives of cafferoylqunic acid on stress hormone-induced depressive behavior and their underlying mechanisms are uncertain. In the current study, we showed that diCQAs reduced depressive behaviors including memory loss in corticosterone (CORT) treated mice. The mechanism of anti-depressants of diCQAs is likely through reduction of ROS production by inhibiting the activity of monoamine oxidase (MAO) type A and B in neurons and astrocytes. Among diCQAs, 3,4- and 3,5-diCQA significantly inhibited the activity of MAO enzymes followed by the reduction of ROS in neurons and astrocytes and also protected neuronal atrophy and synaptic transmission against stress hormone. These results suggest that 3,4- and 3,5-diCQAs effectively reduced depressive symptoms and inhibited ROS production to alleviate memory loss in stress hormone-induced depressive mice and hence, which provide some potential natural antidepressants.

Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor.

We had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABAA-benzodiazepine (BZD) receptor. Among the constituents of phlorotannin, dieckol is a major marine polyphenol from the brown alga Ecklonia cava. Although phlorotannins are known to exert hypnotic effects, the sleep-enhancing effect of dieckol has not yet been determined. We evaluated the effect of dieckol on sleep-wake state of mice by analyzing electroencephalograms (EEGs) and electromyograms. Flumazenil, a GABAA-BZD antagonist, was used to investigate the molecular mechanism underlying the effects of dieckol on sleep. The polygraphic recordings and corresponding hypnograms revealed that dieckol accelerated the initiation of non-rapid eye movement sleep (NREMS); it shortened sleep latency and increased NREMS duration. According to the change in time-course, dieckol showed sleep-enhancing effects by increasing the amount of NREMS and decreasing wakefulness during the same hours. Additionally, sleep quality was evaluated by analyzing the EEG power density, and dieckol was found to not affect sleep intensity while zolpidem was found to reduce it. Finally, we treated mice with zolpidem or dieckol in combination with flumazenil and found the latter to inhibit the sleep-enhancing effect of dieckol and zolpidem, thereby indicating that dieckol exerts sleep-enhancing effects by activating the GABAA-BZD receptor, similar to zolpidem. These results implied that dieckol can be used as a promising herbal sleep aid with minimal side effects, unlike the existing hypnotics.

Memory-enhancing effects of Ishige foliacea extract: In vitro and in vivo study.

Ishige foliacea is used as a functional food in East-Asian countries. We evaluated the memory-enhancing effect of an ethanol extract of I. foliacea (EEI) using in vitro and in vivo models. In vitro acetylcholinesterase and ß-secretase inhibitory activities, antioxidant properties, and neuroprotective effects against human neuronal cell death by H2 O2 and ß-amyloid (Aß) were investigated. We explored the memory-enhancing effect and its underlying mechanism in a mouse model of scopolamine (SCO)-induced memory deficits. EEI showed free radical scavenging and acetylcholinesterase and ß-secretase inhibition activities. Additionally, EEI significantly decreased neuronal cell death induced by H2 O2 or Aß in human neuroblastoma SH-SY5Y cells. In behavior tests, SCO-induced memory deficits was improved by EEI administration. EEI increased the protein expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) and phosphorylated extracellular signal-regulated kinase, which are related to synaptic plasticity in the hippocampus. EEI may ameliorate memory deficits and prevent neurodegenerative disorders. PRACTICAL APPLICATIONS: As the population ages, dementia, a neurodegenerative disease, is becoming an important problem. Various Alzheimer's drugs have been developed based on the disease mechanism, but alternative treatments are required because of the low bioavailability and hepatotoxicity of current medications. Ishige foliacea is a type of brown algae containing various bioactive substances. Phlorotannins, known as brown algae polyphenols, have been studied for their various functionalities such as, anticancer, anti-obesity, antioxidant, and sleep improvement effects, and have attracted attention as raw materials for developing new natural products. We found that the EEI mitigates SCO-induced damage by protecting neurons from oxidative stress-induced cell damage, controlling synthesis mechanisms of the causative agents of AD, and activating BDNF-TrkB-ERK signaling to promote memory function in the hippocampus. The results of this study can serve as a foundation for further research. Additionally, I. foliacea may be useful for treating and improving AD.

Administration of Asian Herb Bennet (Geum japonicum) Extract Reverses Depressive-Like Behaviors in Mouse Model of Depression Induced by Corticosterone.

Geum japonicum, commonly known as Asian herb bennet, has been used as a diuretic, astringent, anti-dizziness, and anti-headache agent in traditional medicine. Since the antidepressant-like effects of G. japonicum extract have not been well studied, we examined the antidepressant-like effects of G. japonicum extract using depressive-like behavior induced in mice through daily injection of corticosterone (CORT). ICR mice (male, 8 weeks old) were treated with CORT (40 mg/kg, i.p.) and orally administered using oral gavage needles with G. japonicum extract (30, 100, and 300 mg/kg) for 4 weeks. Behavioral experiments were performed 1 h after administration. The control mice exhibited a significant increase in the immobility times in the tail suspension and forced swim tests as well as the step-through latency time in the passive avoidance test. Further, the control group showed a significant decrease in their sucrose consumption. However, treatment with G. japonicum extract at doses of 100 and 300 mg/kg significantly improved these depression-like behaviors without altering the locomotor activity. Moreover, treatment with G. japonicum extract significantly prevented the decrease in the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, G. japonicum extract had neuroprotective effects against CORT-induced neurotoxicity in SH-SY5Y cells. Our study indicates that G. japonicum extract exhibits antidepressant-like activity in CORT-induced depressive mice, which might be as a result of increased BDNF expression.

3-Carene, a Phytoncide from Pine Tree Has a Sleep-enhancing Effect by Targeting the GABAA-benzodiazepine Receptors.

3-Carene, a bicyclic monoterpene, is one of the major components of the pine tree essential oils. It has been reported that, in addition to its known properties as a phytoncide, 3-carene has anti-inflammatory, antimicrobial, and anxiolytic effects. We have previously demonstrated that α-pinene, the major component of pine tree, has a hypnotic effect through GABAA-benzodiazepine (BZD) receptors. However, a hypnotic effect of 3-carene has not been studied yet. Here, we report that oral administration of 3-carene increases the sleep duration and reduces sleep latency in pentobarbital- induced sleep test. 3-Carene potentiates the GABAA receptor-mediated synaptic responses by prolonging the decay time constant of inhibitory synaptic responses. These enhancing effects of 3-carene are reproduced by zolpidem, a modulator for GABAA-BZD receptor, and fully inhibited by flumazenil, an antagonist for GABAA-BZD receptor. The molecular docking of 3-carene to the BZD site of GABAA protein structure, suggests that 3-carene binds to the BZD site of α1 and ϒ2 subunits of GABAA-BZD receptor. These results indicate that, similar to α-pinene, 3-carene shows a sleep-enhancing effect by acting as a positive modulator for GABAA-BZD receptor.

Rice bran extract supplement improves sleep efficiency and sleep onset in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study.

We previously reported that rice bran extract supplement (RBS) administration to mice decreased sleep latency and induced non-rapid eye movement (NREM) sleep via inhibition of the histamine H1 receptor. Based on this, we performed the first clinical trial to investigate whether RBS would be beneficial to subjects with disturbed sleep. We performed a randomized, double-blinded, placebo-controlled, 2-week study. Fifty subjects with sleep disturbance were enrolled and received either RBS (1,000 mg/day) or placebo. Polysomnography was performed, and Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale were administered at the initiation and termination of the study. Compared with the placebo, RBS led to significant polysomnographic changes, including decreased sleep latency (adjusted, P = 0.047), increased total sleep time (P = 0.019), and improved sleep efficiency (P = 0.010). Additionally, the amount of stage 2 sleep significantly increased in the RBS group. When adjusted for caffeine intake, wakefulness after sleep onset, total wake time, and delta activity tended to decrease in the RBS group. RBS administration decreased ESS scores. There were no reported serious adverse events in both groups. RBS improved sleep in adults with sleep disturbance. Trial registration: WHO ICTRP, KCT0001893.