• Microbiology and Biotechnology Letters
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• v.44 no.3
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• pp.268-277
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• 2016

This study aimed to investigate the anti-inflammatory effect of the ethanol extract from Chondrus ocellatus Holmes (COHEE) in RAW 264.7 cells and in a mouse ear edema model, by measuring the production of lipopolysaccharide-induced inflammatory response mediators. There were no cytotoxic effects on the proliferation of macrophages treated with COHEE compared with the control. COHEE inhibited the production of nitric oxide and pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-α, and IL-1β]. The extract also reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB p65, and phosphorylated mitogen-activated protein kinase in a dose-dependent manner. In the croton-oil-induced ear edema model, COHEE decreased the formation of mouse ear edema at the highest dose compared with the control, and histological analysis revealed that the epidermal/dermal tissue thickness and mast cell numbers were reduced. Therefore, these results suggest that COHEE may be a promising topical anti-inflammatory therapeutic material through its action of modulating NF-κB and the MAPK signaling pathway.

• Korean Journal of Medicinal Crop Science
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• v.16 no.5
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• pp.349-355
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• 2008

Anticancer and immuno-modulatory activities of methanol extracts from different parts, bark, wood and leaf, of Cornus macrophylla Wall. were investigated in this study. All extracts at a concentration of 1.0mg/ml showed relativity low cytotoxicities on human normal kidney cell (HEK293) by approximately 25%. Bark extract of C. macrophylla showed the highest anticancer activity on human lung cancer cell line (A549) and human breast cancer cell line (MCF-7) by 57.4% and 58.7%, respectively, at a concentration of 1.0mg/ml. All extracts enhanced the growth of human B and T cells, showing 38.7% and 65.9% increase compared to control, respectively, by 5 days incubation with bark extract. The secretions of interleukin 6 (IL6) and tumor necrosis factor alpha (TNF-$\alpha$) from human B and T cells were significantly increased by extracts, especially bark extract. B or T cell medium, which contains cytokines (IL 6 and TNF-$\alpha$) secreted by bark extract treatment for 5 days, time-dependently enhanced the growth of NK-92MI cells with the maximal effect at 5th day of incubation. These results suggest that C. macrophylla, especially bark, has the potential for anticancer and immuno-modulatory activities.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1552-1559
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• 2013

Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.733-741
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• 2008

In the present study, we comprehensively examined the associations of plasma levels of total adiponectin and high molecular weight (HMW) adiponectin with the features of cardiometabolic risks including body fat distribution, dyslipidemia, insulin resistance and inflammatory markers in a cross-sectional study of 110 treated hypertensive patients. Blood lipid profiles, high sensitivity C-reactive protein (hsCRP) and homeostasis model assessment of insulin resistance (HOMA- IR) derived from fasting glucose and insulin concentrations were determined. Plasma levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were analyzed using ELISA. The results showed that plasma levels of HMW-adiponectin were negatively associated with body mass index (BMI, r = - 0.203, p < 0.05) and waist circumference (r = -0.307, p < 0.01), which was not shown in total adiponectin. Plasma levels of HMW-adiponectin were negatively associated with triglyceride (r = -0.223, p < 0.05) and positively associated with HDL-cholesterol (r = 0.228, p < 0.05). Plasma levels of adiponectin were positively associated with HDL-cholesterol (r = 0.224, p < 0.05). Plasma levels of HMW-adiponectin were negatively associated with hsCRP (r = -0.276, p < 0.01) and IL-6 (r = -0.272, p < 0.01). In addition, there were weak associations between plasma levels of HMWadiponectin and TNF-${\alpha}$ (r = -0.163, p = 0.07) and ICAM-1 (r = -0.158, p = 0.09). However, there were no significant associations of total adiponectin with inflammatory markers except hsCRP (r = -0.203, p < 0.05). Stepwise multiple linear regression analysis showed that only plasma levels of HMW-adiponectin was an independent factor influencing serum levels of hsCRP, a marker of systemic low grade inflammation, after adjusting for age, gender, BMI, waist circumference, alcohol intake, smoking status, blood lipids, total adiponectin and drug use (p < 0.01). These results suggest that HMW-adiponectin, rather than total adiponectin, is likely to be closely associated with the features of cardiometabolic risks in treated hypertensive patients and might be effective biomarker for the prediction of cardiovascular disease.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.37 no.3
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• pp.199-210
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• 2011

This study was conducted to develop functional sources of herbal cosmetics for treatment of skin aging and inflammatory disorders using volatile flavor extracts of four different herbal medicinal prescriptions including Cnidium officinale Makino (COM), Angelica gigas Nakai (AGN), Mentha arvense L. (MAL), Artemisiae argyi Folium (AAF), Paeonia lactiflora Pall (PLP), Rehmanniae Radix Preparata (RRP), Scutellaria baicalensis Georgi (SBG), Panax ginseng C.A. Meyer (PGM), Glycyrrhiza uralensis Fisch (GUF). The volatile flavor extracts of four different herbal medicinal prescriptions (HH-1: COM, AGN, PLP, RRP, HH-2: COM, AGN, PLP, RRP, SBG, PGM, GUF, HH-3: COM, AGN, MAL, AAF, HH-4: COM, AGN, MAL, AAF, SBG, PGM, GUF) were extracted using SDE and their antioxidant and anti-inflammatory effects were measured by using DPPH radical and SLO, respectively. As a result, HH-2 showed moderate DPPH radical scavenging activity (68.24 %) and the strongest SLO inhibitory activity (83.96 %) at 100 ${\mu}g$/mL. Moreover, HH-2 of four different prescriptions significantly inhibited NO production on LPS-stimulated RAW 264.7 cells in a dose-dependent manner without considerable cell cytotoxicity at range of 2.0 ~ 50 ${\mu}g$/mL. Additionally, HH-2 also effectively suppressed the production of $PGE_2$ and IL-6, which are responsible for promoting the inflammatory process. Major volatile components of HH-2 were identified as eugenol, paeonol, butyl phthalide, ${\beta}$-eudesmol and butylidene dihydrophthalide by GC-MS analysis. Thus, these results suggest that HH-2 may be useful as a potential source of anti-inflammatory agents in herbal medicinal cosmetics.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.231-237
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• 2010

Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

• Journal of Life Science
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• v.29 no.5
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• pp.596-606
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• 2019

The study investigated the physiochemical properties and the antioxidant and anti-inflammatory activities of the sea tangle (Saccharina japonica) in a water extract before (STWE) and after (STFL) fermentation with Lactobacillus brevis. The pH values of STWE and STFL were 6.18 and 4.16, and the sugar contents were $8.50^{\circ}Brix$ and $7.40^{\circ}Brix$, respectively. The main free amino acids of STWE and STFL were glutamic acid, aspartic acid, and alanine, and the ${\gamma}$-amino butyric acid (GABA) content was increased by fermentation. The total polyphenol contents of STWE and STFL were 498.29 and 615.77 mg gallic acid equivalent (GAE)/ml, respectively. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities of STWE and STFL were markedly increased in a dose-dependent manner, and revealed about 89.89% and 96.94% activities, respectively, at 10% concentration (p<0.05). The superoxide dismutase (SOD) activities of STWE and STFL were also markedly increased in a dose-dependent manner, and the activity of STFL was significantly increased when compared with STWE (p<0.05). The anti-inflammatory activity was examined in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. STWE and STFL decreased the production of reactive oxygen species (ROS), which had levels of about 189.90% and 174.69% at 1% concentration, respectively (p<0.05). The contents of pro-inflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were decreased more by addition of STFL than by addition of STWE. The STWE and STFL showed high antioxidant and anti-inflammatory activity, and these activities were increased by fermentation. Therefore, sea tangle extracts can be used as functional food materials.

• Journal of Life Science
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• v.31 no.3
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• pp.287-297
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• 2021

Cornus officinalis Siebold & Zucc. is traditionally used as an edible and medicinal plant in many countries in East Asia. Previous studies have shown the pharmacological potential of extracts and components of C. officinalis, but comparative analysis of the composition of the leaf, stem, and fruit extracts has been insufficient to date. In the present study, the content of active antioxidant and anti-inflammatory ingredients was verified in different C. officinalis parts (under-ripe sansuyu, ripe sansuyu, seed, leaf, stem, and dried sansuyu). One active component, morroniside, was high in fruit (under-ripe and ripe sansuyu), while loganin was high in fruit (under-ripe sansuyu) and cornin was high in seeds. Total polyphenol contents were highest in fruit (ripe sansuyu) and flavonoids were highest in leaves. DPPH radical scavenging activity was highest in leaves, followed by seeds and then ripe sansuyu extract. The anti-inflammatory efficacy of leaf extracts of C. officinalis (LCO) was further investigated by measuring their effects on levels of nitric oxide (NO) and the pro-inflammatory cytokines interleukin (IL)-1β and IL-6 in RAW 264.7 macrophages. Non-cytotoxic concentrations of LCO effectively decreased the lipopolysaccharide (LPS)-induced expression of inducible NO synthase, resulting in decreased NO production. LCO also significantly suppressed LPS-induced production and expression of IL-1β and IL-6. Taken together, the present findings suggest that C. officinalis leaves have potential as natural materials for the development of antioxidant and anti-inflammatory agents.

• Journal of Applied Biological Chemistry
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• v.64 no.2
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• pp.185-192
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• 2021

Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.861-869
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• 1998

Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.