Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide-induced oxidative stress.

This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells subjected to 300 µM hydrogen peroxide (H2O2)-induced oxidative stress. Furthermore, at a concentration of 200 µg/mL, it significantly reduced the increase in reactive oxygen species production and calcium ion (Ca2+) influx induced by H2O2 by 46.1% and 46.2%, respectively. Similarly, the hydrolysate significantly decreased the levels of p-tau, a hallmark of tauopathy, and BCL2 associated X (BAX), a proapoptosis factor, while increasing the protein levels of choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, brain-derived neurotrophic factor (BDNF), a nerve growth factor, and B-cell lymphoma 2 (BCL2, an antiapoptotic factor. Furthermore, it increased nuclear factor erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1(HO-1) signaling, which is associated with the antioxidant response, while reducing the activation of mitogen-activated protein kinase (MAPK) signaling pathway components, namely phosphor-extracellular signal-regulated kinases (p-ERK), phosphor-c-Jun N-terminal kinases (p-JNK), and p-p38. Column chromatography and tandem mass spectrometry analysis identified LDIQK as a compound with neuroprotective effects in WPH; it inhibited Ca2+ influx and regulated the BAX/BCL2 ratio. Collectively, WPH containing LDIQK demonstrated neuroprotective effects against H2O2-induced neuronal cell damage, suggesting that WPH or its active peptide, LDIQK, may serve as a potential edible agent for improving cognitive dysfunction.

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.

Heukharang lettuce (Lactuca sativa L.) leaf extract displays sleep-promoting effects through GABAA receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Although lettuce is traditionally known to have hypnotic and sedative effects, to date, only a few studies have documented its sleep-promoting effects and elucidated the related mechanisms. AIM OF THE STUDY: We aimed to investigate the sleep-promoting activity of Heukharang lettuce leaf extract (HLE) with increased lactucin content, known as a sleep-promoting substance in lettuce, in animal models. MATERIALS AND METHODS: To evaluate the effect of HLE on sleep behavior, analysis of electroencephalogram (EEG), gene expression of brain receptors, and activation mechanisms using antagonists were investigated in rodent models. RESULTS: High-performance liquid chromatography analysis showed that HLE contained lactucin (0.78 mg/g of extract) and quercetin-3-glucuronide (1.3 mg/g of extract). In the pentobarbital-induced sleep model, the group administered 150 mg/kg of HLE showed a 47.3% increase in sleep duration time as compared to the normal group (NOR). The EEG analysis showed that the HLE significantly increased non-rapid eye movement (NREM), where delta waves were improved by 59.5% when compared to the NOR, resulting in increased sleep time. In the caffeine-induced arousal model, HLE significantly decreased the awake time increased by caffeine administration (35.5%) and showed a similar level to NOR. In addition, HLE increased the gene and protein expression of gamma-aminobutyric acid receptor type A (GABAA), GABA type B, and 5-hydroxytryptamine (serotonin) receptor 1A. In particular, in comparison to the NOR, the group administered 150 mg/kg HLE showed an increase in expression levels of GABAA and protein by 2.3 and 2.5 times, respectively. When the expression levels were checked using GABAA receptor antagonists, HLE showed similar levels to NOR, as the sleep duration was reduced by flumazenil (45.1%), a benzodiazepine antagonist. CONCLUSIONS: HLE increased NREM sleep and significantly improved sleep behavior due to its action on the GABAA receptors. The collective findings suggest that HLE can be used as a novel sleep-enhancing agent in the pharmaceutical and food industries.

Chemical compositions and sleep-promoting activities of hop (Humulus lupulus L.) varieties.

Among natural products with sleep-promoting activity, hops have been used since ancient times as a tranquilizer and hypnotic agent. This study investigated the sleep-promoting effects of extracts of various hop (Humulus lupulus L.) varieties in invertebrate and vertebrate models. The content of α-acids, ß-acids, and xanthohumol was higher in hop 70% alcohol extracts than in hop hot water extracts. Among the alcohol extracts, Citra contained a high α-acid content (229.32 µg/mg), while Saphir showed high ß-acid and xanthohumol content (66.37 and 4.23 µg/mg, respectively). In Drosophila melanogaster, Simcoe and Mosaic water extracts and Saphir and Simcoe alcohol extracts significantly increased total nighttime sleep. Total sleep time of mice with pentobarbital-induced sleep was significantly increased by Simcoe and Mosaic water extracts and Saphir and Simcoe ethanol extracts compared to the normal group. Oral administration of Simcoe water extract and Saphir alcohol extract improved sleep in the caffeine-induced insomnia model and upregulated the mRNA expression of GABAA (gamma 2 subunit) and GABAB receptors in mouse brains. Additionally, Saphir alcohol extract significantly increased the GABA content in mouse brains. Simcoe water extract and Saphir ethanol extract modulated GABAergic signaling to improve sleep-related behaviors, including sleep duration.

Sleep-promoting activity of lotus (Nelumbo nucifera) rhizome water extract via GABAA receptors.

CONTEXT: The sleep-promoting activity of Nelumbo nucifera Gaertn. (Nymphaeaceae) alkaloids in leaves or seeds are well known. However, the sleep-promoting activity of the lotus rhizome (LE), which is used mainly as food, has not yet been evaluated. OBJECTIVE: We investigated the sleep-promoting activity of LE water extract. MATERIALS AND METHODS: Institute of Cancer Research (ICR) mice (n = 8) were subject to a pentobarbital-induced sleep test to assess changes in sleep latency and duration following the administration of LE (80-150 mg/kg). In addition, electroencephalography analysis was performed to determine the sleep quality after LE treatment as well as the sleep recovery effect of LE using a caffeine-induced insomnia SD rat model. Real-time PCR and western blot analysis were performed to investigate the expression of neurotransmitter receptors, and the GABAA receptor antagonists were used for receptor binding analysis. RESULTS: An oral administration of 150 mg/kg LE significantly increased sleep duration by 24% compared to the control. Furthermore, LE increased nonrapid eye movement (NREM) sleep by increasing theta and delta powers. In the insomnia model, LE increased sleep time by increasing NREM sleep. Moreover, treatment with picrotoxin and flumazenil decreased the sleep time by 33% and 23%, respectively, indicating an involvement of the GABAA receptor in the sleep-enhancing activity of LE. The expression of GABAA receptors and the concentration of GABA in the brain were increased by LE. DISCUSSION AND CONCLUSIONS: The results suggest that the sleep-promoting activity of LE was via the GABAA receptor. Collectively, these data show that LE may promote sleep.

Effects of Sphingomyelin-Containing Milk Phospholipids on Skin Hydration in UVB-Exposed Hairless Mice.

Reactive oxygen species (ROS) generated by ultraviolet (UV) exposure cause skin barrier dysfunction, which leads to dry skin. In this study, the skin moisturizing effect of sphingomyelin-containing milk phospholipids in UV-induced hairless mice was evaluated. Hairless mice were irradiated with UVB for eight weeks, and milk phospholipids (50, 100, and 150 mg/kg) were administered daily. Milk phospholipids suppressed UV-induced increase in erythema and skin thickness, decreased transepidermal water loss, and increased skin moisture. Milk phospholipids increased the expression of filaggrin, involucrin, and aquaporin3 (AQP3), which are skin moisture-related factors. Additionally, hyaluronic acid (HA) content in the skin tissue was maintained by regulating the expression of HA synthesis- and degradation-related enzymes. Milk phospholipids alleviated UV-induced decrease in the expression of the antioxidant enzymes superoxidase dismutase1 and 2, catalase, and glutathione peroxidase1. Moreover, ROS levels were reduced by regulating heme oxygenase-1 (HO-1), an ROS regulator, through milk phospholipid-mediated activation of nuclear factor erythroid-2-related factor 2 (Nrf2). Collectively, sphingomyelin-containing milk phospholipids contributed to moisturizing the skin by maintaining HA content and reducing ROS levels in UVB-irradiated hairless mice, thereby, minimizing damage to the skin barrier caused by photoaging.

Effects of Collagen-Tripeptide and Galacto-oligosaccharide Mixture on Skin Photoaging Inhibition in UVB-exposed Hairless Mice.

Collagen-tripeptide (CTP) and galacto-oligosaccharide (GOS), which improve collagen homeostasis and barrier function in the skin, are widely used in the food industry to improve wrinkle-related parameters and skin health. In this study, the photoprotective effect of CTP/GOS mixtures (3:1, 1:1, and 1:3) in ultraviolet (UV) B-irradiated hairless mice was examined. Skin parameter analysis, histological approaches, molecular biology techniques and HPLC analysis were applied to investigate the photoaging protective effect, signaling pathways and changes in the microbiota. Oral administration of CTP/GOS mixtures ameliorated photoaged physical parameters and serum levels of pro-inflammatory cytokines compared to UV-irradiated control group. Administration of the 1:3 mixture showed significant changes in the extracellular matrix-related gene expression compared to other mixture groups. The cecal short-chain fatty acid (SCFA) content showed a significant increase in the CTP/GOS mixed group with a higher GOS content than the control group. In the 16S rRNA-based analysis of cecal microbiota, the relative abundance ratio of the Akkermansia genus belonging to the Verrucomicrobia phylum was higher in CTP and GOS mixture-administered groups than in the UV-irradiated control group. Taken together, CTP/GOS mixtures showed a synergistic effect on photoprotective activity through changes in the gene expression, cytokine levels and intestinal microbiota composition.

Photoprotective effects of sphingomyelin-containing milk phospholipids in ultraviolet B-irradiated hairless mice by suppressing nuclear factor-κB expression.

Ceramide-containing phospholipids improve skin hydration and barrier function and are ideal for use in skin care products. In this study, we evaluated the photoprotective effect of milk phospholipids on the skin condition of UVB-irradiated hairless mice. Skin parameters were assessed following oral administration of milk phospholipids. The UVB irradiation induced photoaging in mice. The animals were divided into 5 groups: a control group (oral administration of saline with no UBV irradiation), UVB group (oral administration of saline with UVB irradiation), and 3 UVB irradiation groups receiving the milk phospholipids at 3 different concentrations of oral administration, 50 mg/kg (ML group), 100 mg/kg (MM group), and 150 mg/kg (MH group), for 8 wk. An increase in skin hydration and transepidermal water loss were improved in the 150 mg/kg of milk phospholipid-administered group. Hematoxylin and eosin staining revealed a decrease in epidermal thickness in the milk phospholipid-administered groups (50, 100, and 150 mg/kg of body weight). In particular, the 100 and 150 mg/kg groups showed significant changes in the area, length, and depth of the wrinkles compared with the UVB group. Moreover, the gene expression of matrix metalloproteins was attenuated, and that of proinflammatory cytokines, especially tumor necrosis factor-α, was significantly reduced in the milk phospholipid-administered groups than in the UVB group. The reduced ceramide and increased sphingosine-1-phosphate levels in the skin tissue due to UVB exposure were restored to levels similar to those of the control group following milk phospholipid administration. These results were confirmed to be due to the downregulation of protein expression of nuclear factor kappa-B (NF-κB) and phosphorylated IκB-α (inhibitor of κB α). Collectively, oral administration of milk phospholipids improves skin health through a synergistic effect on photoprotective activity.

Changes in the component sugar and immunostimulating activity of polysaccharides isolated from Dendrobium officinale in the pretreatments.

BACKGROUND: To isolate polysaccharides with enhanced immunostimulatory activity from Dendrobium officinale, which is used as a herbal medicine in China and Southeast Asia, D. officinale (DO) was pretreated with organic solvents (DOOS) or puffing at 7.5 and 9.0 kgf (7.5DO and 9DO). Hot-water extracts (DOOS-HW, 7.5DO-HW and 9DO-HW) were prepared from each pretreated DO, along with non-pretreated DO, and crude polysaccharides (DO-CP, DOOS-CP, 7.5DO-CP and 9DO-CP) were fractionated from each hot-water extract using ethanol (five volumes). RESULTS: When their immunostimulatory activities were compared by macrophage stimulation and intestinal immune system modulation via Peyer's patches, DOOS-CP showed more potent activity than DO-CP. However, crude polysaccharides fractionated from puffed DO showed significantly lower activity than non-puffed DO and DOOS. The most active polysaccharide contained 95% or more neutral sugar, and the composition ratio of mannose and glucose was 3.0, whereas the lowest polysaccharide content was 2.0 or less. In addition, DOOS-CP was a somewhat refined fraction containing a major peak, representing a molecular weight of 250 kDa, despite being a crude polysaccharide. CONCLUSION: These results suggest that pretreatment of D. officinale with organic solvents may enhance the immunostimulatory activity of polysaccharides and affect the mannose/glucose ratio of polysaccharides, which plays an important role in immunostimulation. © 2021 Society of Chemical Industry.

GABAA Receptor-Mediated Sleep-Promoting Effect of Saaz-Saphir Hops Mixture Containing Xanthohumol and Humulone.

Hops contain flavonoids that have sedative and sleep-promoting activities such as α-acid, ß-acid, and xanthohumol. In this study, the sleep-enhancing activity of a Saaz-Saphir hops mixture was measured. In the caffeine-induced insomnia model, the administration of a Saaz-Saphir mixture increased the sleep time compared to Saaz or Saphir administration alone, which was attributed to the increase in NREM sleep time by the δ-wave increase. Oral administration of the Saaz-Saphir mixture for 3 weeks increased the γ-amino butyric acid (GABA) content in the brain and increased the expression of the GABAA receptor. As the GABA antagonists picrotoxin and bicuculline showed a decrease in sleep activity, it was confirmed that the GABAA receptor was involved in the Saaz-Saphir mixture activity. In addition, the GABAA receptor antagonist also reduced the sleep activity induced by xanthohumol and humulone contained in the Saaz-Saphir mixture. Therefore, xanthohumol and humulone contained in the Saaz-Saphir mixture showed sleep-promoting activity mediated by the GABAA receptors. The mixture of the Saaz and Saphir hop varieties may thus help mitigate sleep disturbances compared to other hop varieties.

Evaluation of Safety through Acute and Subacute Tests of Galacto-Oligosaccharide (GOS).

Acute and subacute toxicity tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by ß-galactosidase derived from Bacillus circulans. Toxicity was evaluated by single dose oral administration (5,000 mg/kg) and was repeated at day 28 (1,000 mg/kg) in male and female Sprague-Dawley rats. In acute toxicity tests, the protein levels of male rats administered GOS showed a significant difference from controls, but remained within the normal range. There were no GOS-related changes in clinical symptoms, weight, food intake, hematology, blood chemistry, relative organ weight, or severe pathology in rats treated with GOS compared with controls. The no observed adverse effect level of GOS was at least 1,000 mg/kg/d in both male and female rats. Bovine-specific genes were not detected in GOS 70%-based products (NeoGOS-P70, NeoGOS-L70, and organic GOS), indirectly showing the absence of an allergen and that products containing GOS 70% are non-toxic and allergen-free.

Changes in Locomotor Activity and Oxidative Stress-Related Factors after the Administration of an Amino Acid Mixture by Generation and Age.

Amino acids, as nutrients, are expected to improve sleep disorders. This study aimed to evaluate the generation- and age-dependent sleep-improving effects of γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) coadministration. The differentially expressed genes and generation-related behavior after the administration of a GABA/5-HTP mixture were measured in a Drosophila model, while age-related changes in gene expression and oxidative stress-related parameters were measured in a mouse model. The GABA/5-HTP-treated group showed significant behavioral changes compared to the other groups. Sequencing revealed that the GABA/5-HTP mixture influenced changes in nervous system-related genes, including those involved in the regulation of the expression of behavioral and synaptic genes. Additionally, total sleep time increased with age, and nighttime sleep time in the first- and third-generation flies was significantly different from that of the control groups. The GABA/5-HTP mixture induced significant changes in the expression of sleep-related receptors in both models. Furthermore, the GABA/5-HTP mixture reduced levels of ROS and ROS reaction products in an age-dependent manner. Therefore, the increase in behavioral changes caused by GABA/5-HTP mixture administration was effective in eliminating ROS activity across generations and ages.

Antioxidant and Immunostimulatory Activities of a Submerged Culture of Cordyceps sinensis Using Spent Coffee.

Spent coffee grounds (SCG) are inexpensive materials that have been used as a source of antioxidants and polysaccharides with immunostimulatory activity. In this study, we performed a microbial fermentation of SCG using Cordyceps sinensis and investigated the radical scavenging and immunostimulatory activity of fermented SCG. SCG fermentation using C. sinensis was performed at 25 °C for 8 d. The polyphenol content of the fermented SCG increased from 1022.4 to 1562.0 µg/mL. The glucosamine content of the mycelia also continuously increased during fermentation. The main polyphenol compounds of fermented SCG were chlorogenic acid and p-coumaric acid, which were increased by fermentation. Fermented SCG also showed significantly higher content of chlorogenic acid isomers than unfermented SCG. The fermented SCG exhibited significantly higher 2,2-diphenyl-2-picrylhydrazyl hydrate (half maximal inhibitory concentration: IC50, 0.37 mg/mL) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (IC50, 0.93 mg/mL) radical scavenging activities than those of the control (0.54 mg/mL and 1.20 mg/mL, respectively; p < 0.05). The fermented SCG stimulated macrophages and promoted the production of various immunostimulatory cytokines (IL-12, IL-6, and TNF-α) compared to control; therefore, microbial fermentation of SCG using C. sinensis is an effective means of generating antioxidant and immunostimulatory materials.

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.

Effects of Green Lettuce Leaf Extract on Sleep Disturbance Control in Oxidative Stress-Induced Invertebrate and Vertebrate Models.

This study investigated the effect of ethanol-extracted green lettuce leaf (GLE) on sleep behavior in physical stress-induced invertebrate and vertebrate models. In Drosophila melanogaster, the group that experienced vibration stress showed decreased sleep time compared to the no-vibration-stress control group, but the GLE treatment group recovered this lost sleep time. The GLE group also recovered the gene expression of downregulated superoxide dismutase induced by vibration stress conditions. According to electroencephalography analysis of rats, non-rapid eye movement (NREM) sleep significantly decreased with a decrease in sleep time for the group in which immobilization stress was induced. In the GLE group (120 mg/kg), the change in sleep pattern caused by stress was restored, and NREM sleep increased by 68.8%, improving overall sleep quality. In addition, GLE upregulated the expression levels of oxidation-related factors and γ-aminobutyric acid (GABAA) receptor. Quercetin-3-glucuronide (Q3G) was evaluated as a sleep-promoting active substance contained in GLE using the pentobarbital-induced sleep test and showed the effect of prolonged sleep time. Q3G inhibited [3H]-flumazenil binding in a concentration-dependent manner with GLE. Taken together, the results indicate that GLE effectively binds to the GABAA receptor to promote sleep, demonstrating the potential of Q3G as an active substance.

Effect of Deer Antler Extract on Muscle Differentiation and 5-Aminoimidazole-4-Carboxamide Ribonucleoside (AICAR)-Induced Muscle Atrophy in C2C12 Cells.

The effect of deer antler extract on muscle differentiation and muscle atrophy were evaluated to minimize muscle loss following aging. Various deer antler extracts (HWE, hot water extract of deer antler; FE, HWE of fermented deer antler; ET, enzyme-assisted extract of deer antler; UE, extract prepared by ultrasonication of deer antler) were evaluated for their effect on muscle differentiation and inhibition of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced muscle atrophy in C2C12 cells. Morphological changes according to the effect of antler extracts on muscle differentiation were confirmed by Jenner-Giemsa staining. In addition, the expression levels of genes related to muscle differentiation and atrophy were confirmed through qRT-PCR. In the presence of antler extracts, the length and thickness of myotubes and myogenin differentiation 1 (MyoD1) and myogenic factor 5 (Myf5) gene expression were increased compared to those in the control group (CON). Gene expression of AMP-activated protein kinase (AMPK), MyoD1, and myogenin, along with the muscle atrophy factors muscle RING finger-1 (MuRF-1) and forkhead box O3a (FoxO3a) upon addition of deer antler extracts to muscle-atrophied C2C12 cells was determined by qRT-PCR after treatment with AICAR. The expression of MuRF-1 and FoxO3a decreased in the groups treated with antler extracts compared to that in the group treated with AICAR alone. In addition, gene expression of MyoD1 and myogenin in the muscle atrophy cell model was significantly increased compared that into the CON. Therefore, our findings indicate that antler extract can increase the expression of MyoD1, Myf5 and myogenin, inhibit muscle atrophy, and promote muscle differentiation.

Effect of capsaicinoids in hot pepper powder on microbial community and free sugar during kimchi fermentation.

Effect of capsaicinoids in hot pepper powder (HP) contains various chemical compounds, including capsaicin and dihydrocapsaicin, which are the main ingredients of the spicy taste. To evaluate the effect of HP on the microbial community in kimchi fermentation, kimchi [kimchi-HP, kimchi-HPE and kimchi-HPER made by adding HP, HP alcohol extract (HPE) and HPE residues (HPER)] was fermented at 4°C for 28 days. The pH and titratable acidity of the samples and the number of bacteria changed with fermentation time. Kimchi-HPER had significantly higher total viable and lactic acid bacteria (LAB) than other samples after 28 days of fermentation. The capsaicinoids content did not differ before and after fermentation, whereas the major free sugar content decreased, and the mannitol content increased. The principal component analysis (PCA) biplots showed similar patterns between kimchi-HP and -HPE. It was confirmed that Leuconostoc and Weissella were related to the initial fermentation, and Lactobacillus was involved in late fermentation. Kimchi-HP and kimchi-HPE increased the ratio of Lactobacillus sakei and decreased that of Leuconostoc mesenteroides compared to kimchi-HPER. Overall, these results revealed that capsaicinoids contained in HP affected Lactobacillus proliferation and mannitol increase during kimchi fermentation.

Quercetin-3-O-glucuronide in the Ethanol Extract of Lotus Leaf (Nelumbo nucifera) Enhances Sleep Quantity and Quality in a Rodent Model via a GABAergic Mechanism.

Current pharmacological treatments for insomnia carry several and long-term side effects. Therefore, natural products without side effects are warranted. In this study, the sleep-promoting activity of the lotus leaf (Nelumbo nucifera) extract was assessed using ICR mice and Sprague Dawley rats. A pentobarbital-induced sleep test and electroencephalogram analysis were conducted to measure sleep latency time, duration, and sleep architecture. The action mechanism of the extract was evaluated through ligand binding experiments. A high dose (300 mg/kg) of the ethanolic lotus leaf extract significantly increased sleep duration compared to the normal group (p < 0.01). Administration of low (150 mg/kg) and high doses (300 mg/kg) of the extract significantly increased sleep quality, especially the relative power of theta waves (p < 0.05), compared to the normal group. Furthermore, caffeine and lotus leaf extract administration significantly recovered caffeine-induced sleep disruption (p < 0.001), and the sleep quality was similar to that of the normal group. Additionally, ligand binding assay using [3H]-flumazenil revealed that quercetin-3-O-glucuronide contained in the lotus leaf extract (77.27 µg/mg of extract) enhanced sleep by binding to GABAA receptors. Collectively, these results indicated that the lotus leaf extract, particularly quercetin-3-O-glucuronide, exhibits sleep quantity- and quality-enhancing activity via the GABAergic pathway.

Stimulating effect of whey protein hydrolysate on bone growth in MC3T3-E1 cells and a rat model.

This study was conducted to investigate the effect of whey protein hydrolysate (WPH) on osteogenic cell differentiation and its growth-promoting effects in rats. Alkaline phosphatase (ALP) activity and calcium deposition were measured by treating MC3T3-E1 cells with WPH, and mRNA and protein levels of factors related to osteoblast differentiation were assessed. ALP activity and calcium deposition were significantly increased in the WPH group (p < 0.001). These findings were confirmed by the upregulation of ALP, bone morphogenic protein, bone sialoprotein, and collagen at the mRNA and protein levels. Furthermore, to confirm the growth-promoting effect of WPH, bone growth was analyzed by administering 3-week-old Sprague-Dawley rats with whey protein or WPH. Moreover, serum levels of calcium, ALP, and insulin-like growth factor-1 (IGF-1) were analyzed, bone analysis was performed using micro-CT, and the size of the growth plate was measured by Cresyl violet staining. When rats were administered with a high dose of WPH (600 mg per kg per day), calcium levels decreased significantly, while ALP levels (1.14-fold; p < 0.01), IGF-1 levels, tibia length, and growth plate height increased significantly compared to those in the control group. Collectively, WPH has shown to be effective in bone differentiation and bone growth.

Prebiotics/Probiotics Mixture Induced Changes in Cecal Microbiome and Intestinal Morphology Alleviated the Loperamide-Induced Constipation in Rat.

The aim of this study was to investigate the effect of a mixture of multi-strain probiotics and prebiotics on loperamide-induced constipation in Sprague-Dawley rats. A multi-strain probiotics alone (loperamide-induced group with multi-strain probiotics mixture group; Lop-Pro) and a mixture of multi-strain probiotics and prebiotics (loperamide-induced group with multi-strain probiotics and prebiotics mixture group; Lop-Pro/Pre) were administered orally after inducing constipation. The fecal water content was significantly higher (by 42%) in the Lop-Pro/Pre group (33.5%) than in the loperamide-induced group (Lop) (23.7%) (p<0.05). The intestinal mucosal thickness, crypt cell area, and interstitial cells of Cajal area were significantly higher in the Lop-Pro/Pre group compared to the Lop group by 16.4%, 20.6%, and 42.3%, respectively. Additionally, the total short-chain fatty acid content was significantly increased in the Lop-Pro and Lop-Pro/Pre groups by 56.4% and 54.2%, respectively, compared with the Lop group. The Lop-Pro and Lop-Pro/Pre groups recovered loperamide-induced alteration in Bacteroidetes and Verrucomicrobia abundance among intestinal microbiota, whereas the Lop-Pro/Pre group recovered Akkermansia, Lactobacillus, Clostridium, Bacteroides, and Oscillibacter abundance. Moreover, the relative abundance of Oscillibacter and Clostridium was significantly different in the Lop-Pro/Pre group compared to the Lop group. Collectively, administration of synbiotics rather than multi-strain probiotics alone is effective in alleviating constipation.