Effects of Dendropanax morbiferus Leaf Extract on Sleep Parameters in Invertebrate and Vertebrate Models.

Dendropanax morbiferus is highly valued in traditional medicine and has been used to alleviate the symptoms of numerous diseases owing to its excellent antioxidant activity. This study aimed to evaluate the sleep promotion and related signaling pathways of D. morbiferus extract (DE) via behavioral analysis, molecular biological techniques, and electrophysiological measurements in invertebrate and vertebrate models. In Drosophila, the group treated with 4% DE experienced decreased subjective nighttime movement and sleep bout and increased total sleeping time. Moreover, substantial changes in locomotor activity, including distance moved, velocity, and movement, were confirmed in the 4% DE-treated group. Compared to Drosophila in which insomnia and oxidative stress were induced by exposure to 0.1% caffeine, the DE-treated group improved sleep-related parameters to the level of the normal group. In the Drosophila model, exposure to 4% DE upregulated the expression of gamma-aminobutyric acid (GABA)-related receptors and serotonin receptor (5-HT1A), along with the expression of antioxidant-related factors, glutathione, and catalase. In the pentobarbital-induced sleep test using ICR mice, the duration of sleep was markedly increased by high concentration of DE. In addition, through the electroencephalography analysis of SD-rats, a significant increase in non-rapid-eye-movement sleep and delta waves was confirmed with high concentrations of DE administration. The increase in sleep time and improvement in sleep quality were confirmed to be related to the expression of altered GABA receptors and the enhancement of the contents of the neurotransmitters GABA and serotonin (5-HT) because of high DE administration. High-dose administration of DE also increased the expression of antioxidant-related factors in the brain and significantly decreased malondialdehyde content. Taken together, DE induced improvements in sleep quantity and quality by regulating neurotransmitter content and related receptor expression, along with high antioxidant activity, and may have a therapeutic effect on sleep disorders.

Sleep-Enhancing Effect of Water Extract from Jujube (Zizyphus jujuba Mill.) Seeds Fermented by Lactobacillus brevis L32.

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.

Sleep-promoting activity of amylase-treated Ashwagandha (Withania somnifera L. Dunal) root extract via GABA receptors.

Ashwagandha (Withania somnifera L. Dunal), an Indian medicinal plant that has been used for centuries to treat insomnia, exhibits a variety of biological activities, such as improving cognitive function, immunity and anxiety. In this study, the effect of enzyme-treated Ashwagandha root extract (EA) and on sleep was evaluated using rodent models. Starch contained in the Ashwagandha root extract was removed by amylase treatment to prepare EA. To evaluate the sleep-promoting activity of EA, a pentobarbital-induced sleep test and electroencephalogram analysis were performed. In addition, the sleep-promoting mechanism of EA was elucidated by analyzing the expression of sleep-related receptors. In the pentobarbital-induced sleep test, EA dose-dependently increased sleep duration. Additionally, electroencephalogram analysis revealed that EA significantly increased δ-wave and non-rapid eye movement sleep times, which are involved in deep sleep, thereby improving sleep quality and quantity. EA also effectively relieved caffeine-induced insomnia symptoms. Furthermore, the γ-aminobutyric acid (GABA) content in the brain and mRNA and protein expression of GABAA, GABAB1, and serotonin receptors were significantly increased by EA compared to the normal group. In particular, EA showed sleep-promoting activity by binding to various GABAA receptor sites. Collectively, EA exhibited sleep-promoting activity through the GABAergic system and may be used as a functional material to improve sleep deprivation.

Effects of gypenoside L-containing Gynostemma pentaphyllum extract on fatigue and physical performance: A double-blind, placebo-controlled, randomized trial.

This study was conducted to investigate the effect of Gynostemma pentaphyllum extract containing gypenoside L (GPE) on improving the cognitive aspects of fatigue and performance of the motor system. One hundred healthy Korean adults aged 19-60 years were randomized to the treatment (GPE for 12 weeks) and control groups, and efficacy and safety-related parameters were compared between the two groups. Maximal oxygen consumption (VO2 max) and O2 pulse were significantly higher in the treatment group than in the control group (p = 0.007 and p = 0.047, respectively). After 12 weeks, the treatment group showed significant changes such as decreases in the levels of free fatty acids (p = 0.042). In addition, there were significant differences in the rating of perceived exertion (RPE) (p < 0.05) and value of temporal fatigue between the treatment and control groups on the multidimensional fatigue scale (p < 0.05). Moreover, the level of endothelial nitric oxide synthase (eNOS) in the blood was significantly higher in the treatment group than in the control group (p = 0.047). In summary, oral administration of GPE has a positive effect on resistance to exercise-induced physical and mental fatigue.

Anti-depressant effects of ethanol extract from Cannabis sativa (hemp) seed in chlorpromazine-induced Drosophila melanogaster depression model.

CONTEXT: Depression is a severe mental illness caused by a deficiency of dopamine and serotonin. Cannabis sativa L. (Cannabaceae) has long been used to treat pain, nausea, and depression. OBJECTIVE: This study investigates the anti-depressant effects of C. sativa (hemp) seed ethanol extract (HE) in chlorpromazine (CPZ)-induced Drosophila melanogaster depression model. MATERIALS AND METHODS: The normal group was untreated, and the control group was treated with CPZ (0.1% of media) for 7 days. The experimental groups were treated with a single HE treatment (0.5, 1.0, and 1.5% of media) and a mixture of 0.1% CPZ and HE for 7 days. The locomotor activity, behavioural patterns, depression-related gene expression, and neurotransmitters level of flies were investigated. RESULTS: The behavioural patterns of individual flies were significantly reduced with 0.1% CPZ treatment. In contrast, combination treatment of 1.5% HE and 0.1% CPZ significantly increased subjective daytime activity (p < 0.001) and behavioural factors (p < 0.001). These results correlate with increased transcript levels of dopamine (p < 0.001) and serotonin (p < 0.05) receptors and concentration of dopamine (p < 0.05), levodopa (p < 0.001), 5-HTP (p < 0.05), and serotonin (p < 0.001) compared to those in the control group. DISCUSSION AND CONCLUSIONS: Collectively, HE administration alleviates depression-like symptoms by modulating the circadian rhythm-related behaviours, transcript levels of neurotransmitter receptors, and neurotransmitter levels in the CPZ-induced Drosophila model. However, additional research is needed to investigate the role of HE administration in behavioural patterns, reduction of the neurotransmitter, and signalling pathways of depression in a vertebrate model system.

Nelumbo nucifera promotes non-rapid eye movement sleep by regulating GABAergic receptors in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Nelumbo nucifera are used in folk medicine for anti-depressant, anti-convulsant, neuroprotective, and many other purposes. AIM OF THE STUDY: The present work evaluated the sleep potentiating effects of water extract from lotus seed in rat, and the neuropharmacological mechanisms underlying these effects. MATERIALS AND METHODS: Pentobarbital-induced sleep test and electroencephalogram (EEG) analysis were applied to investigate sleep latency, duration, total sleeping time and sleep quality of Lotus extract. In addition, real-time PCR and HPLC analysis were applied to analyze the signaling pathway. RESULTS: We found that the amounts of the possible active compounds GABA (2.33 mg/g) and L-tryptophan (2.00 mg/g) were higher than quinidine (0.55 mg/g) and neferine (0.16 mg/g) in lotus seed extract. High dose (160 mg/kg) administration of lotus extract led to a tendency towards decreased sleep latency time and an increase in sleep duration time compared to the control group in a pentobarbital-induced sleep model (p < 0.05). After high dose administration, total sleep and NREM were significantly increased compared to control, while wake time and REM were significantly decreased. Lotus extract-treated rats showed significantly reduced wake time and increased sleep time in a caffeine-induced model of arousal. The transcription level of GABAA receptor, GABAB receptor, and serotonin receptor tended to increase with dose, and lotus extract showed a strong dose-dependent binding capacity to the GABAA receptor. CONCLUSION: The above results strongly suggest that GABA contained in lotus seed extract acts as a sleep potentiating compound, and that sleep-potentiating activity involves GABAA receptor binding.

Amylase-Producing Maltooligosaccharide Provides Potential Relief in Rats with Loperamide-Induced Constipation.

Constipation is a chronic disease caused by infrequent, inadequate, and difficult bowel movements. The present study aimed to evaluate the potential laxative effect of maltooligosaccharide (MOS) on loperamide-induced constipation in a rat model. In vitro experiments were conducted to evaluate the effect of MOS on the growth of lactic acid bacteria. Moreover, to examine the effect of MOS administration on Sprague-Dawley (SD) rats with loperamide-induced constipation, the drinking water for the rats was supplemented with 10% or 15% of MOS for 14 days, and, thereafter, the improvement in constipation was assessed. For this, the rats were divided into five groups: normal (Nor), loperamide-induced constipated (Con), positive control (15% of dual-oligosaccharide (DuO-15)), 10% MOS treated (MOS-10), and 15% MOS-treated (MOS-15). In an in vitro test, MOS treatment promoted the growth of lactic acid bacteria except Lactobacillus bulgaricus. Treatment with higher MOS dose relieved constipation in rats by improving the fecal pellet and water content. Furthermore, in the high MOS dose group, the cecal short-chain fatty acid levels significantly increased compared to those in the control group (P < 0.001). MOS treatment also improved the mucosal thickness as well as mucin secretion and increased the area of intestinal Cajal cells compared to that in the control group (P < 0.001). These findings suggest that MOS relieves constipation and has beneficial effect on the gastrointestinal tract, and, therefore, it can be used as an ingredient in functional foods for treating constipation or improving intestinal health.

Tannase-Converted Green Tea Extract with High (-)-Epicatechin Inhibits Skeletal Muscle Mass in Aged Mice.

The objective of this study was to investigate the effects of tannase-converted green tea extract on body composition, muscle oxidative stress-related factors, and differentiation-related factors. The mean bone-related parameters and body composition were determined by the live dual-energy X-ray absorptiometry (DEXA). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to determine mRNA expression and protein levels, respectively. The results of total mass testing in the epicatechin control (EC) and middle concentration tannase-converted green tea extract (T 1) intake groups were not significantly different compared with those in the control group; however, the high-concentration tannase-converted green tea extract (T 2) group showed a significantly higher effect to the lean than that of all other groups (p < 0.05). The results of the assay of muscle differentiation-related genes indicated that the expression levels in the EC and T 1 groups (p < 0.05) and the expression levels in the T 2 group (p < 0.01) were significantly different in the bicep femoris compared with that in the control group. The results of the SOD gene assay indicate that the expression levels in the EC and T 1 groups (p < 0.05) and the expression level in the T 2 group (p < 0.01) were significantly different in the bicep femoris compared with that in the control group. Additionally, SOD gene expression in the T 2 group was significantly increased (p < 0.05) in the soleus compared with that in the control, EC and T 1 groups. Our results suggest that tannase-converted green tea extract prevents muscle loss and regulates the quantity and quality of muscle by the levels of antioxidant stress-related enzymes and muscle differentiation factors to a greater extent than the administration of epicatechin and middle dose green tea extract.

Effects of tannase-converted green tea extract on skeletal muscle development.

BACKGROUND: The aim of this study was to investigate the effect of tannase-converted green tea extract with a high (-)-epicatechin (EC), (-)-epigallocatechin (EGC), and gallic acid (GA) content on myotube density and fusion in normal and oxidative stress-induced C2C12 skeletal muscle cells. Although the use of green tea extract is considered beneficial, cellular and molecular mechanisms of action of tannase-converted green tea extracts that are used as potential muscle growth materials have not been thoroughly studied. METHODS: This study used histological analysis and molecular biology techniques, and compared the results with those for AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribonucleoside (AICAR) and green tea extracts. RESULTS: The myotube density of normal and oxidative stress-induced C2C12 cells was significantly higher in the tannase-converted green tea extract-treated group than that observed in the other groups (normal cells: P < 0.01; oxidative stress-induced cells: P < 0.05). In addition, tannase-converted green tea extract and green tea extract treatments significantly upregulated the genetic expression of myogenin, Myf5, and MyoD (P < 0.05). The levels of AMP-activated protein kinase-α (AMPKα) and muscle RING-finger protein-1 (MuRF-1) in the tannase-converted green tea extract group were higher than those in the AICAR and green tea extract groups (P < 0.05). CONCLUSIONS: Taken together, our findings describe that the high levels of EC, EGC, and GA in the tannase-converted green tea extract are attributable to the morphological changes in C2C12 cells and intercellular signaling pathways. Therefore, tannase-converted green tea extract can be used in the treatment of sarcopenia.

Effectiveness of the Sleep Enhancement by Green Romaine Lettuce (Lactuca sativa) in a Rodent Model.

This study was conducted to investigate the effects of the extracts of green romaine lettuce (GRE) on sleep enhancement. GRE contains 1071.7 and 199.2 µg/g of extracts of lactucin and lactucopicrin, respectively, known as sleep enhancement substances. When 100 mg/kg of GRE was administered orally, sleep latency and duration time were significantly increased compared to controls (p < 0.05). Rapid eye movement (REM) sleep decreased with 100 mg/kg of GRE administration and non-REM (NREM) sleep also increased. There was no significant difference between REM and NREM among the oral GRE administration groups receiving 100, 120, and 160 mg/kg GRE. In the caffeine-induced insomnia model, total sleep time was significantly increased by 100 mg/kg GRE administration compared to the caffeine-treated group (p < 0.05). In addition, GRE inhibited the binding of [3H]-flumazenil in a concentration-dependent manner, and affinity of both lactucin and lactucopicrin to gamma-aminobutyric acid (GABA)A-benzodiazepine (BDZ) receptor was 80.7% and 55.9%, respectively. Finally, in the pentobarbital-induced sleep mouse model, the sleep enhancement effect of GRE was inhibited by flumazenil, an antagonist of BDZ. Thus, these results demonstrate that GRE acts via a GABAergic mechanism to promote sleep in a rodent model.

Enzymatic hydrolysis increases ginsenoside content in Korean red ginseng (Panax ginseng CA Meyer) and its biotransformation under hydrostatic pressure.

BACKGROUND: Enzymatic hydrolysis and high hydrostatic pressure (HHP) are common processing techniques in the extraction of active compounds from food materials. The aim of this study was to investigate the effects of enzymatic hydrolysis combined with HHP treatments on ginsenoside metabolites in red ginseng. RESULTS: The yield and changes in the levels of polyphenol and ginsenoside were measured in red ginseng treated with commercial enzymes such as Ultraflo L, Viscozyme, Cytolase PCL5, Rapidase and Econase E at atmospheric pressure (0.1 MPa), 50 MPa, and 100 MPa. ß-Glucosidase activity of Cytolase was the highest at 4258.2 mg-1 , whereas Viscozyme showed the lowest activity at 10.6 mg-1 . Pressure of 100 MPa did not affect the stability or the activity of the ß-glucosidase. Treatment of red ginseng with Cytolase and Econase at 100 MPa significantly increased the dry weight and polyphenol content of red ginseng, compared with treatments at 0.1 MPa and 50 MPa (P < 0.05). The amounts of ginsenoside and ginsenoside metabolites derived from red ginseng processed using Cytolase were higher than those derived from red ginseng treated with the other enzymes. Treatment with Cytolase also significantly increased the skin and intestinal permeability of red ginseng-derived polyphenols. CONCLUSION: Cytolase could be useful as an enzymatic treatment to enhance the yield of bioactive compounds from ginseng under HHP. In addition, ginsenoside metabolites obtained by Cytolase hydrolysis combined with HHP are functional substances with increased intestinal and skin permeability. © 2019 Society of Chemical Industry.

Effects of probiotic supplementation on post-infectious irritable bowel syndrome in rodent model.

BACKGROUND: Probiotics have been reported to be the active component used in the treatment of many functional gastrointestinal symptoms and syndromes. Lactobacillus and yeast culture are extensively used in probiotic supplements and traditional treatments for irritable bowel syndrome (IBS). The aim of this study was to investigate the effects of probiotic treatments (Lactobacillus acidophilus LA5, Bifidobacterium animalis subsp. lactis BB12 and Saccharomyces cerevisiae var. boulardii) on the behavioral response, targeted gene expression and pro-inflammatory cytokine levels of Pi (Post infectious)-IBS -induced mice. METHODS: Pathogen-free male C57L/B6 mice and the Trichinella-infected mice were used to measure the score of abdominal withdrawal reflex (AWR). To compare molecular, biological and biochemical evidences of given probiotics with normal and positive control groups in mice, we conducted quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blotting, and cytokine analysis. RESULTS: Pi-IBS-induced immune response was confirmed that PAR-2 mRNA level was significantly increased by Trichinella infection (P < 0.05). The reduction of Pi-IBS symptoms through Trichinella infection and the effects of given probiotics were confirmed by a change in the protein levels of cytokines (P < 0.05). In addition, the administration of DW (Daewon) probiotics significantly decreased serum levels of IL-1 and IL-6 (P < 0.05). CONCLUSIONS: We have demonstrated that the given probiotics decreased pro-inflammatory cytokine levels in both the control and Pi-IBS induced mice. Taken all the results together, the results support that DW probiotics has a potential as a probiotic medication for patient with IBS via regulating TNF-α and IL-6 protein levels and serum IL-1 and IL-6 levels.

GABA and l-theanine mixture decreases sleep latency and improves NREM sleep.

CONTEXT: γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABAA receptors favours sleep. l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits. OBJECTIVE: This study investigated the potential synergistic sleep enhancement effect of GABA/l-theanine mixture. MATERIALS AND METHODS: Pentobarbital-induced sleep test was applied to find proper concentration for sleep-promoting effect in ICR mice. Electroencephalogram (EEG) analysis was performed to investigate total sleeping time and sleep quality in normal SD rats and caffeine-induced awareness model. Real-time polymerase chain reaction (RT-PCR) was applied to investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture involved transcriptional processes. RESULTS: GABA/l-theanine mixture (100/20 mg/kg) showed a decrease in sleep latency (20.7 and 14.9%) and an increase in sleep duration (87.3 and 26.8%) compared to GABA or theanine alone. GABA/l-theanine mixture led to a significant increase in rapid eye movement (REM) (99.6%) and non-REM (NREM) (20.6%) compared to controls. The use of GABA/l-theanine mixture rather than GABA or l-theanine alone restored to normal levels sleep time and quality in the arousal animal model. The administration of GABA/l-theanine led to increased expression of GABA and the glutamate GluN1 receptor subunit. CONCLUSIONS: GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of GABA/l-theanine combination, which seems to affect sleep behaviour.

Romaine Lettuce/Skullcap Mixture Improves Sleep Behavior in Vertebrate Models.

The aim of this study is to investigate the effects of romaine lettuce leaves extract (RE), skullcap root extract (SE) and their mixture on sleep behaviors in vertebrate models. HPLC analysis showed that RE contains lactucopicrin (0.02±0.01 mg/g extract), chlorogenic acid (4.05±0.03 mg/g extract), caffeic acid (2.38±0.03 mg/g extract), and chicoric acid (7.02±0.32 mg/g extract) as main phenolic compounds, while SE includes baicalin (99.4±0.5 mg/g extract), baicalein (8.28±0.21 mg/g extract), and wogonin (3.09±0.32 mg/g extract). The mixture of RE (100 mg/g extract) and SE (40 mg/g extract) increased total sleep time by 50.9% compared with the control in pentobarbital-induced sleep model. In electroencephalography (EEG) analysis, RE/SE mixture significantly increased Non-Rapid Eye Movement (NREM), in which delta wave was enhanced by around 40% compared with normal control, leading to the increase of sleep time. In caffeine-induced wake model, RE/SE mixture greatly decreased (53%) caffeine-induced wake time, showing a similar level to normal control. In addition, caffeine-induced decreased of NREM and delta wave effectively increased with RE/SE mixture; NREM and delta wave increased by 85% and 108%, respectively. Furthermore, RE/SE mixture was shown to bind to a gamma-aminobutyric acid type A (GABAA)-benzodiazepine (BZD) receptor stronger than RE or SE single extract. Taken together, RE/SE mixture effectively improved sleep behavior with the increase of NREM via GABAA-BZD receptor binding. RE/SE mixture can be used as an herbal agent for sleep disorders.

Valerian/Cascade mixture promotes sleep by increasing non-rapid eye movement (NREM) in rodent model.

The aim of this study was to investigate the beneficial effect of Valerian/Cascade mixture on sleeping in mammal models. In pentobarbital-induced sleep model, Valerian, Cascade, and Valerian/Cascade mixture significantly reduced the latency time for sleeping, and total sleeping time effectively increased in these sample groups compared with the control. Valerian/Cascade mixture increased sleep duration by 37%. The mixture significantly increased the non-rapid eye movement (NREM) sleep time by 53% compared with the control, while REM sleeping time was decreased by 33% with Valerian/Cascade mixture, in Electroencephalography (EEG) analysis, resulting in the increase of total sleep time and the decrease of awakening. This sleep-promoting effect was obvious in caffeine-induced awakening model; Valerian, Cascade, and the mixture significantly enhanced NREM and total sleep time, which were reduced by caffeine. Caffeine-induced increase of awakening was effectively deceased to the normal level by these three samples. In particular, delta wave responsible for deep sleep in NREM was greatly increased by the mixture in both normal and caffeine-induced awake models. This sleep-promoting effect of Valerian/Cascade mixture was shown to be due to the upregulation of gamma-aminobutyric acid A receptor (GABAAR). Valerian/Cascade mixture showed 91% binding capacity to GABAA-BZD receptor. Two compounds, Valerenic acid and Xanthohumol, were shown to significantly contribute to the binding activity of Valerian/Cascade mixture on the GABA receptor.

Effect of explosion-puffed coffee on locomotor activity and behavioral patterns in Drosophila melanogaster.

We hypothesized that the administration of explosion-puffed coffee, containing γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP), would be associated with a reduction of the caffeine effect on sleep behavior and behavioral patterns, which was investigated in a Drosophila model. The effects of feeding roasted coffee beans (RB), explosion-puffed coffee beans puffed at 0.75MPa and 0.9MPa (PB 7.5 and PB 9.0, respectively), or decaffeinated coffee beans (DeRB) on locomotor activity and behavioral patterns of Drosophila was analyzed. In the decreasing order, the total chlorogenic acid (caffeoylquinic acids, CQA) content was PB 7.5>PB 9.0>RB. PB content analysis showed high levels of GABA and 5-HTP, compared with that of RB, which corresponded with the sleep-wake behavior of Drosophila. The RB and PB (PB 7.5 and PB 9.0) groups were not significantly different with respect to an activity count during the subjective night and day period compared with the normal controls. Sleep bout numbers of the normal, PB, and DeRB groups showed significant differences as compared with the caffeine and RB groups (p<0.05). The PB and DePB groups showed a significantly increased transcript levels for the GABA receptors compared to the caffeine group. The caffeine and RB groups displayed better climbing ability than the other groups, covering an average distance 6cm in the related test; the average distance covered by the normal, PB 7.5, and DeRB groups was <4cm. The normal and DeRB groups showed similar behavior patterns with respect to total distance, velocity, moving, not moving, and meander. However, the PB 7.5 group significantly regulated not moving and meander of flies compared to flies receiving only caffeine and RB. Suppression of the stimulating effect of caffeine by explosion-puffed coffee administration was indicated in the above results, which can be attributed to the increased content of GABA and 5-HTP with explosive puffing process carried out at 0.75MPa. Results of the underlying mechanism of the behavioral change patterns of explosive puffed with or without caffeine in Drosophila models, transcript level for the Dop1-R1 receptor in caffeine group was significantly higher than normal, PB, and DePB groups. Flies exposed to the caffeine had significantly decreased transcript levels for the GABA receptors. PB 7.5 and DePB showed higher level of GABA content than RB.

Effect of Valerian/Hop Mixture on Sleep-Related Behaviors in Drosophila melanogaster.

The aim of this study was to investigate the sleep-promoting effect of a Valerian/Hops mixture in fruit flies. The HPLC analysis showed that Valerenic acid (1260.53 µg/g of extract) and Xanthohumol (Cascade: 827.49 µg/g, Hallertau: 763.60 µg/g, Saaz: 186.93 µg/g) were contained in Valerian and Hop, respectively. The sleep patterns of fruit flies on the Valerian/Hops were examined in both baseline and caffeine-treated conditions. Total activities of flies significantly decreased in 20 mg/mL Valerian (74%), 10 mg/mL Cascade (25%), and 5 mg/mL Hallertau (11%) during nighttime or daytime compared with the control. Valerian/Cascade mixture showed longer sleeping time (ca. 20%) than control group. This mixture-mediated effect was partly observed in caffeine-treated flies. Valerian/Cascade mixture upregulated mRNA expressions of gamma-aminobutyric acid (GABA) receptors and serotonin receptor, and GABA receptors were more strongly regulated than serotonin receptor. In competitive GABA receptor binding assay, Valerian/Cascade mixture extract showed a higher binding ability on GABA receptor than Valerenic acid or/and Xanthohumol which are estimated to be active compounds in the extract. This study demonstrates that a Valerian/Cascade mixture extract improves sleep-related behaviors, including sleeping time, by modulating GABAergic/serotonergic signaling.

Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the emergence of macrolide resistance, concerns about the efficacy of macrolides for the treatment of Mycoplasma pneumoniae (MP) pneumonia in children have been raised. This study aimed to determine the effect of macrolide resistance on the outcome of children who were hospitalized with MP pneumonia. METHODS: Between 2010 and 2015, we performed culture of MP from nasopharyngeal samples obtained from children who were hospitalized with pneumonia at five hospitals in Korea. Macrolide resistance was determined by the analysis of 23S rRNA gene transition and the minimal inhibitory concentrations of four macrolides. Medical records were reviewed to analyze the clinical response to treatment with macrolides. RESULTS: MP was detected in 116 (4.8%) of the 2436 children with pneumonia. MP pneumonia was prevalent in 2011 and 2015. Of the 116 patients with MP pneumonia, 82 (70.7%) were macrolide-resistant. There were no differences in the age distribution, total duration of fever, and chest x-ray patterns between the macrolide-susceptible and macrolide-resistant groups. After macrolide initiation, mean days to defervescence were longer in the macrolide-resistant group than in macrolide-susceptible group (5.7 days vs. 4.1 days, P = 0.021). However, logistic regression analysis revealed that the presence of extrapulmonary signs (P = 0.039), homogeneous lobar consolidation (P = 0.004), or parapneumonic effusion (P < 0.001) were associated with fever duration of ≥7 days after the initiation of macrolides, regardless of macrolide resistance. CONCLUSIONS: This study demonstrated that fever duration in MP pneumonia was determined by the radiologic findings of chest x-ray, not by the presence of macrolide resistance. The results highlight the need for future studies to assess therapeutic benefit from macrolides in the treatment of children with MP pneumonia.

Topical application of spent coffee ground extracts protects skin from ultraviolet B-induced photoaging in hairless mice.

The aim of this study was to evaluate the protective effect of spent coffee ground (SCG) on ultraviolet (UV) B-induced photoaging in hairless mice. The oil fraction (OSCG) and ethanol extract (ESCG) of SCG were prepared from SCG. OSCG contained a much higher level of caffeine (547.32 ± 1.68 µg mg(-1)) when compared to the sum of its chlorogenic acid derivatives (∼119 µg mg(-1)), and pyrazines were the major aromatic compounds in OSCG. OSCG effectively inhibited the UVB-induced increase in intracellular reactive oxygen species in HaCaT cells. Topical application of OSCG or ESCG significantly reduced the UVB-induced wrinkle formation in mice dorsal skin. The combined application of OSCG and ESCG (OEH) led to a decrease in the wrinkle area by over 35% when compared with the UVB-treated control (UVBC). Epidermal thickness was also reduced by 40%. This result was connected to the significant reduction in transdermal water loss (27%) and erythema formation (48%) that result from UVB irradiation. Polarization-sensitive optical coherence tomography (PS-OCT) and antibody-based histological analyses showed that OSCG and ESCG effectively suppressed the UVB-induced decrease in collagen content. The level of type 1 collagen (COL1) in the OEH group was enhanced by around 40% compared with the UVB control group (UVBC). This was attributed to the down-regulation of matrix metalloproteinases (MMP2, 9, and 13), which are known to be responsible for collagen destruction. Our results indicate that topical treatment with OSCG/ESCG protects mouse skin from UVB-induced photoaging by down-regulating MMPs; therefore, suggesting the potential of SCG extracts as a topical anti-photoaging agent.

Photoprotective effects of galacto-oligosaccharide and/or Bifidobacterium longum supplementation against skin damage induced by ultraviolet irradiation in hairless mice.

This study aimed at examining whether oral administration of galacto-oligosaccharide (GOS) and Bifidobacterium longum, individually or in combination, could exert photoprotective effects on the skin of hairless mice. GOS and/or Bifidobacterium were administered orally to hairless mice for 12 weeks. Mice were irradiated with UV light daily for four consecutive days. GOS administration increased the water-holding capacity of the skin and prevented transepidermal water loss compared with the control. A reduction in the erythema formation of 16.8% was also observed in the GOS-treated group compared with the control, and CD44 gene expression was significantly increased. Oral administration of GOS or Bifidobacterium significantly increased TIMP-1 and Col1 mRNA expression compared with the control. Our findings support that prebiotics, including GOS, are beneficial not only to the intestine, but also to the skin, and present the possibility of new nutritional strategies for the prevention of UV-induced skin damage.