Efficacy of Polygonatum sibiricum on Mild Insomnia: A Randomized Placebo-Controlled Trial.

Polygonatum sibiricum (PS) rhizome, which contains glyceryl-1-monolinoleate as its primary active component, has been shown to improve insomnia in animal models. Based on these findings, we aimed to investigate the safety and efficacy of PS rhizome extract in improving sleep quality in individuals with mild insomnia. Eighty individuals with mild insomnia were enrolled in a four-week, randomized, double-blind, placebo-controlled trial of PS rhizome extract (500 mg/day, n = 40, PS group) or placebo (n = 40, placebo group). The primary outcome measure was change in total score on the Athens Insomnia Scale (AIS) to indicate sleep quality. The secondary outcome measures included change in actigraphy data and perfusion levels in the brain regions within the default mode network (DMN), which is known to play a key role in insomnia. The PS group showed greater improvement in the total AIS score with a significant increase in total sleep time, relative to the placebo group. In addition, significant group-by-visit interactions were observed in the perfusion level of the medial prefrontal cortex within the DMN. Findings of the current study provide first evidence that PS rhizome extract could be an effective natural ingredient for improving sleep in mild insomnia using a human model.

Nelumbo nucifera Seed Extract Promotes Sleep in Drosophila melanogaster.

The sleep-promoting effects of the water extract of Nelumbo nucifera seeds (NNE) were investigated in an invertebrate model. The effects of NNE on the subjective nighttime activity, sleep episodes, and sleep time were determined using Drosophila melanogaster and locomotor activity monitoring systems in basal and caffeine-induced arousal conditions. The movements of fruit flies were analyzed using the Noldus EthoVision-XT system, and the levels of neuromodulators were analyzed using HPLC. Expression of neuromodulator receptors was analyzed using real-time PCR. NNE was shown to contain neurotransmission-related components; γ-aminobutyric acid (GABA) (2.33±0.22 mg/g), tryptophan (2.00±0.06 mg/g), quinidine (0.55±0.33 mg/g), and neferine (0.16±0.01 mg/g). The total activity of flies during nighttime was decreased by 52% with 1.0% NNE treatment. In the individual and collective conditions, the subjective nighttime activities (45/38%) and sleep bouts (20/14%) of flies was significantly decreased with NNE treatment, while total sleep times (10/27%) were significantly increased. This sleep-promoting effect is more pronounced in caffeine-treated conditions; the nighttime activity of flies was reduced by 53%, but total sleep time was increased by 60%. Our video-tracking analysis showed a significant decrease of the moving distance and velocity of flies by NNE. This NNE-mediated sleep-promoting effect was associated with up-regulation of GABAA/GABAB and serotonin receptors. The NNE-mediated increase of GABA content was identified in flies. These results demonstrate that NNE effectively promotes sleep in flies by regulating the GABAergic/serotonergic neuromodulators, and could be an alternative agent for sleep promotion.

Deer Bone Extract Supplementation for Mild-to-Moderate Knee Osteoarthritis Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.

In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy of deer bone extract (DBE) in participants with knee osteoarthritis (OA). We enrolled 50 participants aged 50-70 years, having knee OA with a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score ≥5.0. The participants were assigned to the placebo or DBE group (550 mg/day) for 12 weeks. The outcome measures were as follows: pain score on the visual analog scale (VAS); WOMAC score; and blood and urine biomarkers. In the DBE group, VAS scores, WOMAC total scores, and WOMAC subscores (for pain, stiffness, and physical function) improved significantly compared with the baseline values. However, there was no significant difference in outcomes between the DBE and placebo groups. The present findings suggest that DBE may mildly reduce joint pain and stiffness and improve joint function in patients with painful knee OA.

The immune-enhancing activity of Cervus nippon mantchuricus extract (NGE) in RAW264.7 macrophage cells and immunosuppressed mice.

Chemotherapeutics are often used to inhibit the proliferation of cancer cells. However, they can also harm healthy cells and cause side effects such as immunosuppression. Especially traditional oriental medicines long used in Asia, may be beneficial candidates for the alleviation of immune diseases. Cervus nippon mantchuricus extract (NGE) is currently sold in the market as coffee and health drinks. However, NGE was not widely investigated and efficacy remain unclear and essentially nothing is known about their potential immune-regulatory properties. As a result, NGE induced the differentiation of RAW264.7 macrophage cells. NGE-stimulated RAW264.7 macrophage cells elevated cytokines levels and NO production. NGE-stimulated RAW264.7 macrophage cells activated MAPKs and NF-κB signaling pathways. NGE encouraged the immuno-enhancing effects in immunosuppressed short-term treated with NGE mice model. NGE or Red ginseng encouraged the immuno-enhancing effects in immunosuppressed long-term treated with NGE mice model. Our data clearly show that NGE contains immune-enhancing activity and can be used to treat immunodeficiency.

Changes in Drosophila melanogaster Sleep-Wake Behavior Due to Lotus (Nelumbo nucifera) Seed and Hwang Jeong (Polygonatum sibiricum) Extracts.

We evaluated the sleep enhancement activity of the medicinal herbs valerian (Valeriana officinalis), jujube (Ziziphus jujube), lotus seed (Nelumbo nucifera), Gastrodia elata, Polygonatum sibiricum, and baekbokryung (Poria cocos), which can relieve insomnia in a Drosophila model. Locomotor activity was measured in the Drosophila model to evaluate the sleep activity of Korean medicinal herbs traditionally used as sleep aids. The group treated with lotus seed extract showed less nocturnal activity. Treatment with 10 or 20 mg/mL of P. sibiricum significantly reduced nocturnal activity compared to the control group (P<0.05). The activity and sleep bouts of fruit flies were significantly decreased by a high-dose treatment (10 mg/mL) of lotus or P. sibiricum extracts at night. Caffeine-treated Drosophila showed increased nocturnal activity and decreased total sleep time (P<0.05). Flies receiving the 10 mg-doses of lotus seed or P. sibiricum extract showed significantly different nocturnal locomotor activity and total sleep time compared to caffeine-treated Drosophila. Lotus seed and P. sibiricum extracts are attractive and valuable sleep-potentiating nutraceuticals.

Effects of Ganglioside on Working Memory and the Default Mode Network in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial.

This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481).

Deer bone extract prevents against scopolamine-induced memory impairment in mice.

Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aß1-42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine.

Effects of deer bone extract on the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced osteoarthritic rats.

Deer bone extract has the potential to relieve the discomfort or the articular cartilaginous damage associated with osteoarthritic (OA) and may be useful as a natural supplement for OA treatment without serious side effects. We analyzed the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced OA rats. Increases in the levels of serum pro-inflammatory cytokines, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α were significantly inhibited by the administration of deer bone extract (p<0.05). Decreases in the expression of collagen type II (COL2) and tissue inhibitors of metalloproteinases (TIMPs) mRNAs in the cartilage were significantly inhibited by deer bone extract treatment (p<0.05). The deer bone extract significantly suppressed the expression of matrix metalloproteinases (MMPs) mRNAs in the cartilage. The deer bone extract induced the up-regulation of COL2 and TIMP mRNAs and the down-regulation of MMP mRNAs by suppressing the expression of pro-inflammatory cytokine mRNAs.

Deer bone extract suppresses articular cartilage damage induced by monosodium iodoacetate in osteoarthritic rats: an in vivo micro-computed tomography study.

We evaluated the anti-osteoarthritic effects of deer bone extract on articular cartilage damage by using micro-computed tomography (micro-CT) in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in rats. Male Wistar rats (6 weeks of age) were randomly divided into 5 groups (10 rats/group): sham control (SC; PBS injection+PBS 1 mL treatment); negative control (NC; MIA injection+PBS 1 mL treatment); positive control (PC; MIA injection+250 mg/kg glucosamine sulfate/chondroitin sulfate mixture treatment); low dose (LDB; MIA injection+250 mg/kg deer bone extract treatment); and high dose (HDB; MIA injection+500 mg/kg deer bone extract treatment). After 50 days of treatment, we observed that the administration of deer bone extract protected against bone destruction and reduced the number of erosion lacunae. When deer bone extract was administered, the trabecular thickness distribution (Tb.Th) (LDB: 75.9 µm, HDB: 80.7 µm vs. NC: 48.0 µm) and the trabecular bone volume fraction ratio (BV/TV) (LDB: 43.8%, HDB: 48.2% vs. NC: 39.1%) were significantly restored. Additionally, the trabecular separation (Tb.Sp) increase caused by MIA was decreased significantly with the administration of deer bone extract (LDB: 73.4 µm, HDB: 81.2 µm vs. NC: 112.0 µm). We concluded that the oral administration of deer bone extract effectively relieved the morphological changes induced by MIA injection in an animal model.

Neuroprotective action of deer bone extract against glutamate or Aß1₋42-induced oxidative stress in mouse hippocampal cells.

Water extracts of deer bone, called nokgol in Korean, and deer antlers have been traditionally used as anti-aging medicines. Deer antler extract is known to possess various activities, including anti-aging or anti-amnesic activity. However, there are no reports about the neuroprotective effect of deer bone extract (DBE). The objective of this study was to examine the neuroprotective effect of DBE on glutamate-induced cell death of mouse hippocampal cells (HT-22 cells) and to elucidate the mode of neuroprotective action of DBE. In this study, HT-22 cells was pretreated with DBE before stimulation with glutamate, and then, the effects of DBE on cell viability, oxidative stress markers, and MAP kinases were determined. Separately, the effect of DBE on H2O2 or amyloid beta peptide (1-42) (Aß1₋42)-induced cytotoxicity of HT-22 cells was evaluated. DBE protected HT-22 cells from glutamate-induced cell death and prevented the increase in lactate dehydrogenase leakage in HT-22 cells. DBE also prevented glutamate-induced oxidative stress, as indicated by increased reactive oxygen species and lipid peroxidation as well as by decreases in glutathione (GSH) levels and GSH peroxidase activity. In addition, DBE inhibited glutamate-induced activation of c-Jun N-terminal kinases (JNK), p38, and extracellular signal-regulated kinase, indicators of oxidative stress-induced cell death. Furthermore, DBE also protected against H2O2 and Aß1₋42-induced cytotoxicity. These results suggest that DBE may be a useful functional agent for the prevention against neurodegenerative disorders involving oxidative stress.

Effects of black soy peptide supplementation on blood pressure and oxidative stress: a randomized controlled trial.

Black soy peptides have been shown to possess properties that may decrease blood pressure (BP). To examine the effects of black soy peptide supplementation on BP and oxidative stress in subjects with prehypertension or stage I hypertension, 100 participants with an initial untreated systolic blood pressure (SBP) of 130-159 mm Hg, diastolic blood pressure (DBP) of 80-99 mm Hg or both were enrolled. Participants were randomly assigned to either a group ingesting supplement containing 4.5 g black soy peptides daily or a placebo group for 8 weeks. SBP and DBP decreased after 8-week black soy peptide supplementation versus controls (P<0.001). At 8 weeks, SBP decrease was significantly greater for the black soy peptide group (-9.69 ± 12.37 mm Hg) than for the control group (-2.91 ± 13.29 mm Hg) after adjusting for the baseline levels (P = 0.015). Plasma malondialdehyde (MDA) and urinary 8-epi-prostaglandin F2α decreased (P = 0.004 and P = 0.046, respectively) and plasma superoxide dismutase (SOD) activity increased (P<0.001) following 8 weeks of black soy peptide supplementation versus baselines. The MDA decreases (P = 0.022) and SOD activity and nitric oxide (NO) increases (P = 0.022 and P<0.001, respectively) were greater for the black soy peptide group than for the control group. Changes in SBP negatively correlated with changes in NO (r = -0.343, P = 0.001). Changes in angiotensin-converting enzyme activity negatively correlated with NO decreases (r = -0.490, P<0.001) and SOD activity increases (r = -0.338, P = 0.001). Black soy peptide dietary supplementation significantly reduces SBP and oxidative stress in patients with prehypertension and stage I hypertension.

Obesity-related metabolomic analysis of human subjects in black soybean peptide intervention study by ultraperformance liquid chromatography and quadrupole-time-of-flight mass spectrometry.

The present study aimed to identify key metabolites related to weight reduction in humans by studying the metabolic profiles of sera obtained from 34 participants who underwent dietary intervention with black soybean peptides (BSP) for 12 weeks. This research is a sequel to our previous work in which the effects of BSP on BMI and blood composition of lipid were investigated. Sera of the study were subjected to ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and the data were analyzed using partial least-squares discriminate analysis (PLS-DA) score plots. Body mass index and percent body fat of the test group were reduced. Levels of betaine, benzoic acid, pyroglutamic acid, pipecolic acid, N-phenylacetamide, uric acid, l-aspartyl-l-phenylalanine, and lysophosphatidyl cholines (lysoPCs) (C18:1, C18:2, C20:1, and C20:4) showed significant increases. Levels of l-proline, valine, l-leucine/isoleucine, hypoxanthine, glutamine, l-methionine, phenylpyruvic acid, several carnitine derivatives, and lysoPCs (C14:0, PC16:0, C15:0, C16:0, C17:1, C18:0, and C22:0) were significantly decreased. In particular, lysoPC 16:0 with a VIP value of 12.02 is esteemed to be the most important metabolite for evaluating the differences between the 2 serum samples. Our result confirmed weight-lowering effects of BSP, accompanied by favorable changes in metabolites in the subjects' blood. Therefore, this research enables us to better understand obesity and increases the predictability of the obesity-related risk by studying metabolites present in the blood.

Weight reduction effects of a black soy peptide supplement in overweight and obese subjects: double blind, randomized, controlled study.

The present study determined the effect of black soy peptide supplementation on body weight and body fat in overweight/obese subjects. In a double-blind controlled trial, participants (n = 80) were randomized to either soy peptide supplementation (the test group) or to a placebo (the placebo group). Sixty-four people completed the study, and anthropometric parameters, serum inflammatory markers, and leptin and lipid profiles were measured. After 6 weeks, the test group (n = 35) had significant reductions in body weight (p = 0.003) and body mass index (BMI) (p = 0.004), body fat mass (p = 0.038). After 12 weeks, they also had significant reductions in body weight (p < 0.001), BMI (p < 0.001), body fat percentage (p = 0.002), and body fat mass (p = 0.001). However, these significances were not observed in the placebo group (n = 29). In addition, net changes in body weight and body fat mass in the test group were significantly bigger than those in the placebo group after 12 weeks. Leptin levels were significantly reduced in the test groups (p = 0.047), but were not observed in the placebo group (p = 0.323). Interestingly, the subjects with weight reductions ≥1kg in the test group had greater reductions in circulating leptin levels (p = 0.002). Additionally, fasting insulin levels were significantly reduced in the test groups. The conclusion is that black soy peptide supplementation may be beneficial for body weight control in overweight/obese subjects.

Black soy peptide supplementation improves glucose control in subjects with prediabetes and newly diagnosed type 2 diabetes mellitus.

The present study aimed to determine the effect of black soy peptide supplementation on glucose control in subjects with prediabetes (impaired fasting glucose or impaired glucose tolerance) and newly diagnosed type 2 diabetes mellitus (DM). In this double-blind, placebo-controlled study, subjects with prediabetes and type 2 DM were randomly assigned to the placebo control group or the black soy peptide intervention group. We determined fasting serum concentrations of glucose, hemoglobin A1c, insulin, and free fatty acids, performed a 2-hour postload glucose (2-hour PG) test, and compared serum lipid profiles before and after the 12-week supplementation. In particular, subjects with fasting glucose ≥ 110 mg/dL who consumed black soy peptides tended to have lower fasting glucose levels (two-tailed test, P = .098; one-tailed test, P = .049) and had a significant reduction in 2-hour PG level (two-tailed P = .012, one-tailed P = .006), compared with baseline levels. The changes in 2-hour PG levels were also statistically significant in the intervention group (-41.25 ± 13.67 mg/dL) compared with the placebo group (12.42 ± 9.80 mg/dL; two-tailed P = .015, one-tailed P = .008). In contrast, hemoglobin A1c levels were not significantly improved by the dietary intervention. In conclusion, black soy peptide supplementation may be beneficial for controlling fasting blood glucose levels and 2-hour PG levels.