• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.767-774
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• 2011

Defatted green tea seed was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether, ethyl acetate and butanol. The ethanol and butanol extracts showed greater increases in antiproliferation potential against liver cancer cells than petroleum ether, ethyl acetate, $H_2O$, and hot water extracts did. Thus, this study was carried out to investigate the anti-proliferative actions of defatted green tea seed ethanol extract (DGTSE) in HepG2 cancer cells. The DGTSE contained catechins including EGC ($1039.1{\pm}15.2\;g/g$), tannic acid ($683.5{\pm}17.61\;{\mu}g/g$), EC ($62.4{\pm}5.00\;{\mu}g/g$), ECG ($24.4{\pm}7.81\;{\mu}g/g$), EGCG ($20.9{\pm}0.96\;{\mu}g/g$) and gallic acid ($2.4{\pm}0.68\;{\mu}g/g$), but caffeic acid was not detected when analyzed by HPLC. The anti-proliferation effect of DGTSE toward HepG2 cells was 83.13% when treated at $10\;{\mu}g$/mL, of DGTSE, offering an $IC_{50}$ of $6.58\;{\mu}g$/mL. DGTSE decreased CYP1A1 and CYP1A2 protein expressions in a dose-dependent manner. Quinone reductase and antioxidant response element (ARE)-luciferase activities were increased about 2.6 and 1.94-fold at a concentration of $20\;{\mu}g$/mL compared to a control group, respectively. Enhancement of phase II enzyme activity by DGTSE was shown to be mediated via interaction with ARE sequences in genes encoding the phase enzymes. DGTSE significantly (p<0.05) suppressed prostaglandin $E_2$ level, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) protein expressions, and NF${\kappa}$B translocation, but did not affected nitric oxide production. From the above results, it is concluded that DGTSE may ameliorate tumor and inflammatory reactions through the elevation of phase II enzyme activities and suppression of NF${\kappa}$B translocation and TNF-${\alpha}$ protein expressions, which support the cancer cell anti-proliferative effects of DGTSE in HepG2 cells.

• Journal of Life Science
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• v.27 no.11
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• pp.1315-1323
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• 2017

Turmeric is a rhizomatous herbaceous perennial plant (Curcuma longa (CL)) of the ginger family, Zingiberaceae. A yellow-pigmented fraction isolated from the rhizomes of CL contains curcuminoids belonging to the dicinnamoyl methane group. Curcumin is an important active ingredient responsible for the biological activity of CL. However, CL is not usually used as a food source due to its bitter taste. The present study was designed to determine the effect of the CL fermented by Rhizopus oryzae (FCL) on pro-inflammatory factors such as nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), tumor necrosis factor alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cell line. The cell viability was determined by MTT assay. To evaluate the anti-inflammatory effect of FCL 80% EtOH extracts, IL-6 and $TNF-{\alpha}$ were measured by ELISA kit. Also, the amount of $NO/PGE_2/NF-{\kappa}B$ was measured using the $NO/PGE_2/NF-{\kappa}B$ detection kit and the iNOS/COX-2 expression was measured by Western blotting. The results showed that the FCL reduced NO, $PGE_2$, iNOS, COX-2, $NF-{\kappa}B$, IL-6 and $TNF-{\alpha}$ production without cytotoxicity. These results suggest that FCL extracts may be a developed the functional food related to anti-inflammation due to the significant effects on inflammatory factors.

• Journal of Life Science
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• v.24 no.3
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• pp.329-335
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• 2014

Sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus have been widely used in folk medicine for several inflammatory disorders in Korea and China. In this study, we compared the anti-inflammatory effects of the ethanol extracts of S. flavescens (EESF), G. uralensis (EEGU) and D. dasycarpus (EEDS), and their mixtures (medicinal herber mixtures, MHMIXs) on production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Our data indicated that treatment with EESF, EEGU and EEDD significantly inhibited the excessive production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in LPS-stimulated RAW 264.7 cells. The ethanol extracts and MHMIXs also attenuated the production of pro-inflammatory cytokines, including interleukin-$1{\beta}$ ($IL-1{\beta}$) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) by suppressing their protein expression, respectively. Interestingly, MHMIX-1, which basic ingredients are EESF, EEGU and EEDS in the proportion 3:1:1, more safely and effectively inhibits the LPS-induced inflammatory status in LPS-stimulated RAW 264.7 macrophages compared to ethanol extracts of each medicinal herb and other MHMIXs without causing any cytotoxic effects. Our study provides scientific evidence to support that a berbal mixture, MHMIX-1 may be useful in the treatment of inflammatory diseases by inhibiting inflammatory regulator responses in activated macrophages.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.37-45
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• 2019

Portulaca oleracea L. (PL) has been used in traditional medicine herb for treatment of various diseases, such as diarrhea, dysentery, and skin inflammation. Previous studies have shown that the PL regulates the inflammation by inhibition of pro-inflammatory cytokines. Although PL might have improvement effects of intestinal function and bioactive effects, there are not enough studies to demonstrate. This study investigated the effects of KDC16-2 on the improvement of intestinal function and anti-inflammatory effects in vivo and in vitro. The improvement effect of intestinal function was measured fecal amount, water content and intestinal transit rate in KDC16-2 treated ICR mice. As results, compared with the control group, the KDC16-2 group showed a significant increase in wet fecal weight, dry fecal weight and fecal water content. The intestinal transit rate of KDC16-2 group was significantly increased. Based on the results, KDC16-2 is considered to have effects on improving intestinal function. The effect of anti-inflammatory demonstrated by using dextran sulfate sodium (DSS)-induced colitis mice. The mice were administered 3% DSS along with KDC16-2 (100, 300 mg/kg) for 14 days. DSS-induced colitis mice were significantly ameliorated in KDC16-2 treated group, including body weight loss, colon length shortening, tight junction protein of colon and histological colon injury. The levels of inflammatory mediators (IgG2a, IgA, C-reactive protein and Myeloperoxidase) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, Interleukin (IL)-6) which are involved in inflammatory responses were increased in the DSS-treated group as compared to those in the control group, and the levels were significantly decreased in the KDC16-2 groups. In addition, we investigated the impact of KDC16-2 on lipopolysaccharide (LPS)-induced inflammatory responses in J774A.1 cells. KDC16-2 inhibited production of prostaglandin E2 (PGE2) and reactive oxygen species (ROS). These results suggested that the KDC16-2 could effectively alleviate the dysfunction of intestinal and inflammatory mediators. Thus, these KDC16-2 can be potentially used as health functional food of intestinal.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.336-344
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• 2004

Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

• Journal of Life Science
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• v.26 no.5
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• pp.537-544
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• 2016

Barley (Hardeum vulgare L.) sprout has received much attention in recent years as a functional food in many countries, especially in Korea and Japan. It has been reported that barley sprouts are comprised of 52.6% polysaccharides, 34.1% proteins, and 4.97% fats, along with a variety of vitamins, minerals, and polyphenols. The purpose of this study was to assess the anti-oxidant and anti-inflammatory activities of the ethanol extracts of barley sprouts. We examined the inhibitory effect of barley sprout extracts (BSE) on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, and nitric oxide (NO), prostaglandin E₂ (PGE₂) and cytokine production in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophage cells. BSE contains high amounts of phenolics and flavonoids and exhibits potent anti-oxidative activity, as depicted by the DPPH radical-scavenging experiment. The concentration of total phenols was 17.55 μg/ml, and flavonoids, 13.98 μg/ml. We also investigated the anti-inflammatory activities of BSE in LPS-stimulated RAW 264.7 cells. Tumor necrosis factor-alpha and PGE₂ production, which had increased as a result of treatment with LPS, were significantly inhibited by BSE in a dose-dependent manner. BSE also significantly suppressed LPS-induced production of NO, and this was accompanied by a decrease in the expression of the iNOS and COX-2 proteins. These results indicate that barley sprouts may be a highly valuable natural product owing to its high-quality functional components as well as its anti-oxidant and anti-inflammatory activities.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.607-622
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• 2004

Recently epidemiologic studies have indicated that the patients with periodontitis may have increased risk of ischemic cardiovascular events, and have suggested the important roles of blood cytokines and acute reactant proteins in the systemic infection and inflammatory response. Periodontitis and coronary heart disease (CHD) may share the common risk factors and the genetic mechanism associated with interleukin(IL)-1A, B and RA genotype may be involved in the production of IL-1. This study was aimed to investigate the relationship between angiographically defined CHD and periodontitis as chronic Gram-negative bacterial infection and to determine whether the IL-1 gene polymorphism is associated in both diseases. Patients under the age of 60 who had undergone diagnostic coronary angiography were enrolled in this study. Subjects were classified as positive CHD (+CHD, n=37) with coronary artery stenosis more than 50% in at least one of major epicardial arteries, and negative CHD (-CHD, n=30) without significant stenosis. After recording the number of missing teeth, periodontal disease severity was measured by means of plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and radiographic bone loss around all remaining teeth. Gingival crevicular fluid (GCF) was collected from the 4 deepest periodontal pockets and assessed for cytokine ($IL-1{\beta}$, IL-6, IL-1ra, tumor necrosis $factor-{\alpha}$, and prostaglandin $E_2$). Additionally, blood CHD markers, lipid profile, and blood cytokines were analyzed. IL-1 gene cluster genotyping was performed by polymerase chain reaction and enzyme restriction using genomic DNA from buccal swab, and allele 2 frequencies of IL-1A(+4845), IL-1B(+3954), IL-B(-511), and IL-1RA(intron 2) were compared between groups. Even though there was no significant difference in the periodontal parameters between 2 groups, GCF level of $PGE_2$ was significantly higher in the +CHD group(p<0.05). Correlation analysis showed the positive relationship among PD, CAL and coronary artery stenosis(%) and blood $PGE_2$. There was also significant positive relationship between the periodontal parameters (PI, PD, CAL) and the blood CHD markers (leukocyte count, C-reactive protein, and lactic dehyrogenase). IL-1 gene genotyping showed that IL-1A(+3954) allele 2 frequency was significantly higher in the +CHD group compared with the -CHD group (15% vs. 3.3%, OR 5.118,p=0.043). These results suggested that periodontal inflammation is related to systemic blood cytokine and CHD markers, and contributes to cardiovascular disease via systemic inflammatory reaction. IL-1 gene polymorphism might have an influence on periodontal and coronary heart diseases in Korean patients.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.146-156
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• 2018

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.10
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• pp.1371-1377
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• 2012

Biological activities of Korean Panax ginseng 55% ethanol extract (KPGE) were investigated. The measured total polyphenol content of KPGE was 357.45 mg/100 g. KPGE showed the highest ${\alpha},{\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities of 80% and 86% at 1,000 ${\mu}g/mL$, respectively. DPPH and ABTS radical scavenging activities significantly increased in a KPGE concentration-dependent manner. SOD-like activity of KPGE (1, 10, and 100 ${\mu}g/mL$) increased from 22% up to 33% at KPGE concentrations of 500 and 1,000 ${\mu}g/mL$. KPGE treatment significantly suppressed the generation of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and cytokines (tumor necrosis factor-alpha: TNF-${\alpha}$, interleukin-6: IL-6, interleukin-$1{\beta}$: IL-$1{\beta}$), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. KPGE demonstrated strong anti-inflammatory activity that reduced NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells. Even low concentrations of KPGE (1 and 10 ${\mu}g/mL$) reduced $PGE_2$ and NO production in RAW 264.7 macrophages without LPS-stimulation, respectively. At concentrations of 100, 500, and 1,000 ${\mu}g/mL$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production were significantly suppressed. The results of our study suggest the potential of Korean Panax ginseng as an excellent antioxidant substance for inhibiting inflammatory mediators. Therefore, Korean Panax ginseng (KPGE) may be used as a therapeutic approach to various inflammatory diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.501-509
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• 2016

The present study investigated the anti-atopic effects of mixed extracts from date plum, persimmon, and mulberry leaves (DPME) on atopic dermatitis (AD)-like skin lesions in hairless mice. The in vivo results demonstrated that DPME treatment significantly reduced the dermatitis clinical score and epidermal thickness in AD-like skin lesions. Histological analyses showed that DPME treatment strongly inhibited dermal infiltration of inflammatory cells and activity of mast cells in AD-like skin lesions. DPME treatment inhibited production of serum IgE and interluekin (IL)-4 in hairless mice with AD. Moreover, DPME treatment significantly suppressed production of tumor necrosis factor $(TNF)-{\alpha}$ and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. In addition, DPME treatment reduced production of pro-inflammatory mediators (nitric oxide, prostaglandin E2, $TNF-{\alpha}$, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Therefore, the results of this study indicate that the anti-atopic and anti-inflammatory effects of DPME may be involved in the regulation of inflammatory responses, suggesting that DPME may be used as an anti-atopic dermatitis material and natural anti-inflammatory ingredient.