• Sleep Medicine and Psychophysiology
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• v.12 no.1
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• pp.68-71
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• 2005

We report a case of obstructive sleep apnea syndrome, which occurred primarily during the REM sleep stage. A 55-year-old female patient who complained of chronic insomnia on the initial visit turned out to have obstructive sleep apnea syndrome of a mild degree (respiratory disturbance index (RDI) of 13.8/hour, %time spent below 90% of SaO2=5.0%) on nocturnal polysomnography. Interestingly, apnea episodes and desaturations mainly occurred during REM sleep stage. And RDI and destaturations during REM sleep stage were found to be severe enough to classify as a severe degree of obstructive sleep apnea syndrome. These findings suggest that severe obstructive sleep apnea syndrome might be masked under the symptom of chronic insomnia and that apneas can be predominantly localized within REM sleep epochs. In terms of treatment, "REM sleep-dependent" apneas may call for different methods of treatment, especially REM sleep-specific pharmacological intervention.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.58-66
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• 2020

Background: The biological and pharmacological effects of BST204, a fermented ginseng extract, have been reported in various disease conditions. However, its molecular action in metabolic disease remains poorly understood. In this study, we identified the antiadipogenic activity of BST204 resulting from its inhibition of the S6 kinase 1 (S6K1) signaling pathway. Methods: The inhibitory effects of BST204 on S6K1 signaling were investigated by immunoblot, nuclear fractionation, immunoprecipitation analyses. The antiadipogenic effect of BST204 was evaluated by measuring mRNA levels of adipogenic genes and by chromatin immunoprecipitation and quantitative real-time polymerase chain reaction analysis. Results: Treatment with BST204 inhibited activation and nuclear translocation of S6K1, further decreasing the interaction between S6K1 and histone H2B in 10T1/2 mesenchymal stem cells. Subsequently, phosphorylation of H2B at serine 36 (H2BS36p) by S6K1 was reduced by BST204, inducing an increase in the mRNA expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation and promoted myogenic and early osteogenic gene expression. Consistently, BST204 treatment during adipogenic commitment suppressed the expression of adipogenic marker genes and lipid drop formation. Conclusion: Our results indicate that BST204 blocks adipogenesis of mesenchymal stem cells through the inhibition of S6K1-mediated histone phosphorylation. This study suggests the potential therapeutic strategy using BST204 to combat obesity and musculoskeletal diseases.

• Molecules and Cells
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• v.40 no.7
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• pp.466-475
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• 2017

Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates.

• Journal of Microbiology and Biotechnology
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• v.27 no.9
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• pp.1628-1638
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• 2017

Viola tianshanica Maxim, belonging to the Violaceae plant family, is traditionally used in Uighur medicine for treating pneumonia, headache, and fever. There is, however, a lack of basic understanding of its pharmacological activities. This study was designed to observe the effects of the ethanol extract (TSM) from Viola tianshanica Maxim on the inflammation response in acute lung injury (ALI) induced by LPS and the possible underlying mechanisms. We found that TSM (200 and 500 mg/kg) significantly decreased inflammatory cytokine production and the number of inflammatory cells, including macrophages and neutrophils, in bronchoalveolar lavage fluid. TSM also markedly inhibited the lung wet-to-dry ratio and alleviated pathological changes in lung tissues. In vitro, after TSM ($12.5-100{\mu}g/ml$) treatment to RAW 264.7 cells for 1 h, LPS ($1{\mu}g/ml$) was added and the cells were further incubated for 24 h. TSM dose-dependently inhibited the levels of proinflammatory cytokines, such as NO, $PGE_2$, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$, and remarkably decreased the protein and mRNA expression of $TNF-{\alpha}$ and IL-6 in LPS-stimulated RAW 264.7 cells. TSM also suppressed protein expression of $p-I{\kappa}Ba$ and p-ERK1/2 and blocked nuclear translocation of $NF-{\kappa}B$ p65. The results indicate that TSM exerts anti-inflammatory effects related with inhibition on $NF-{\kappa}B$ and MAPK (p-ERK1/2) signaling pathways. In conclusion, our data demonstrate that TSM might be a potential agent for the treatment of ALI.

• Nutrition Research and Practice
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• v.15 no.6
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• pp.686-702
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• 2021

BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E₂ (PGE₂), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE₂, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.344-353
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• 2021

Background: Korean Red ginseng extract (KRGE) has beneficial effects on the cardiovascular system by improving endothelial cell function. However, its pharmacological effect on endothelial cell senescence has not been clearly elucidated. Therefore, we examined the effect and molecular mechanism of KRGE on the senescence of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were grown in normal or KRGE-supplemented medium. Furthermore, they were transfected with heme oxygenase-1 (HO-1) gene or treated with its inhibitor, a NF-κB inhibitor, and a miR-155-5p mimic or inhibitor. Senescence-associated characteristics of endothelial cells were determined by biochemical and immunohistochemical analyses. Results: Treatment of HUVECs with KRGE resulted in delayed onset and progression of senescence-associated characteristics, such as increased lysosomal acidic β-galactosidase and decreased telomerase activity, angiogenic dysfunction, and abnormal cell morphology. KRGE preserved the levels of anti-senescent factors, such as eNOS-derived NO, MnSOD, and cyclins D and A: however, it decreased the levels of senescence-promoting factors, such as ROS, activated NF-κB, endothelial cell inflammation, and p21 expression. The beneficial effects of KRGE were due to the induction of HO-1 and the inhibition of NF-κB-dependent biogenesis of miR-155-5p that led to the downregulation of eNOS. Moreover, treatment with inhibitors of HO-1, NF-κB, and miR-155-5p abolished the anti-senescence effects of KRGE. Conclusion: KRGE delayed or prevented HUVEC senescence through a signaling cascade involving the induction of HO-1, the inhibition of NF-κB-dependent miR-155-5p biogenesis, and the maintenance of the eNOS/NO axis activity, suggesting that it may protect against vascular diseases associated with endothelial senescence.

• The Korea Journal of Herbology
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• v.37 no.3
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• pp.9-19
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• 2022

Objectives : Angelicae Gigantis Radix (AG) is a plant of the Ranunculus family. AG have been reported to have various pharmacological effects on human health which include uterine growth promotion, anti-inflammatory, analgesic, and immune enhancement. However, research on dermatitis disease is insufficient. Therefore, we investigated the effects of AG on tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) stimulated HaCaT cell. Methods : To investigate the effect of AG on HaCaT cell, HaCaT cells were pre-treated with AG for 1 hour and then stimulated with TNF-α/IFN-γ. After 24 hours, media and cells were harvested to analyze the inflammatory mediators. Concentration of human interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α in the media were assessed by ELISA. mRNA expression of human thymus and activation-regulated chemokine (TARC), IL-6, and IL-8 were analyzed by RT-PCR. Additionally, the mechanisms of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were investigated by Western blot. Results : The treatment of AG inhibited gene expression levels of IL-6, IL-8, and TARC and protein expression levels of IL-1β, MCP-1, and GM-CSF. Also, AG significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation and NF-κB translocation in TNF-α/IFN-γ stimulated HaCaT cell. Conclusions : Taken together, these results demonstrate that AG can alleviate inflammatory diseases such as atopic dermatitis by regulating the expression of inflammatory cytokines. Also, it suggest that AG may a promising candidate drug for the treatment of inflammatory disease such as atopic dermatitis.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.17-24
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• 2013

Objectives : This study was to evaluate the single dose toxicity of Persicae Semen (PS) in ICR mice. Methods : Aqueous extracts of PS (Yield = 18.60%) were administered as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) guidelines (2009-116, 2009). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. Results : Amygdalin contents in PS aqueous extracts were detected as $32.50{\pm}5.96{\mu}g/ml$. We could not find any PS extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations up to 2,000 mg/kg in both female and male mice, except for transient and slight loss of locomotion detected in female and male mice treated with 2,000 mg/kg. In addition, pharmacological immunomodulatory effects related findings were also demonstrated in 2,000mg/kg treated female and male mice as hypertrophy and hyperplasia of lymphoid cells in the submandibular lymph nodes. Conclusions : Based on the results of this experiment, the approximate lethal dose (ALD) of PS extracts after single oral treatment in female and male mice were considered above 2,000 mg/kg, respectively. It should be carefully used in clinics because the possibilities of respiratory or neurological disorders were observed when administered over 2,000 mg/kg of PS extract related to amygdalin.

• Journal of Life Science
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• v.32 no.6
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• pp.482-490
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• 2022

Sarcopenia, a geriatric and multifactorial syndrome characterized by progressive systemic skeletal muscle disorder, may be associated with many comorbidities. Sarcopenia caused by a decrease in muscle mass and muscle strength is accompanied by the aggravation of various pathological conditions, and as life expectancy increases, its prevalence will continue to increase in the future. During the aging process, chronic oxidative stress and increased inflammatory responses act as major contributors to skeletal muscle loss. In addition, disruption of autophagy and apoptosis signals associated with dysfunction of mitochondria, which are essential for energy metabolism, accelerates the loss of muscle proteins. The pharmacological effect of cordycepin, a major physiologically active substance in the genus Cordyceps, which has been widely used for the prevention and treatment of various diseases for a long time, is directly related to its antioxidant and anti-inflammatory actions. In this review, we present the correlation between apoptosis, autophagy, protein catabolism, and satellite cell activity important for muscle regeneration using cordycepin for the prevention and treatment of sarcopenia. Although there have been few studies so far on the use of cordycepin for sarcopenia, previous studies suggest that cordycepin may contribute to inhibiting the age-related weakening of mitochondrial function and blocking the breakdown of muscle proteins. In addition, the protective effect of cordycepin on muscle cell damage is considered to be closely related to its antioxidant and anti-inflammatory activities. Therefore, it is considered that more continuous basic research is needed, focusing on the molecular biological mechanism of cordycepin, which is involved in the anti-aging of muscle cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.4
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• pp.30-50
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• 2023

Objectives : To investigate the active compounds and therapeutic mechanisms of Atractylodes Lancea(Thunb.) D.C. and Magnolia Officinalis Rehder et Wilson in the treatment of dermatitis accompanied by pruritus, as well as their potential to complement or replace standard drugs. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of research target herbs. Then we explore pathway/terms of the common target proteins among research target herbs, fexofenadine and disease. Results : We selected 9 active compounds are selected from Atractylodes lancea and identified 231 target proteins. Among them, 74 proteins are associated with inflammatory skin diseases that cause pruritus. These proteins are involved in various pathways including, 'Nitric-oxide synthase regulator activity', 'Hydroperoxy icosatetraenoate dehydratase activity, Aromatase activity', 'RNA-directed DNA polymerase activity', 'Arachidonic acid metabolism', 'Peptide hormone processing', 'Chemokine binding' and 'Sterol biosynthetic process'. Additionally, coregenes are involved in 'IL-17 signaling pathway'. Similarly, we selected 2 active compounds from Magnolia officinalis and identified 133 target proteins. Among them, 33 proteins are related to inflammatory skin diseases that cause pruritus. These proteins are primarily involved in 'Vascular associated smooth muscle cell proliferation' and 'Arachidonic acid metabolism'. There is no significant difference between the pathways in which coregenes are involved. Conclusions : It is expected that Atractylodes Lancea will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied pruritus through suppressing inflammation and protecting skin barrier. Meanwhile, it is expected that Magnolia Officinalis will only be able to show indirect anti-inflammation effects. Therefore, Atractylodes Lancea and fexofenadine are believed to complement each other, whereas Magnolia Officialinalis is expected to provide supplementary support on skin disease.