• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.32-33
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• 2006

There is compelling evidence that chronic inflammation predisposes to biliary tract cancer. Previously we found that aspirin use and variants in the PTGS2 gene, both of which are closely linked to inflammation, were associated with biliary tract cancer risk in a population-based study in China. To test the inflammation hypothesis further, we examined the associations of variants in 20 genes involved in the inflammation pathway with risk of biliary tract cancer and stones in a large population-based case-control study in Shanghai, China. We genotyped 56 single nucleotide polymorphisms (SNPs)from 20 inflammation genes in 411 biliary tract cancer cases (237 gallbladder cancers, 127 extrahepatic bile duct cancers, and 47 ampullary cancers), 895 subjects with biliary stones, and 786 population controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cls) for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer risk. Of the 56 SNPs examined, 20 showed some associations with biliary cancer and stones. Specifically, variants of the IL8, IL8RB, RNASEL, TGF-beta, and TNF-alpha genes were associated with gallstone risk, while variants in the IL1A, IL10, VEGF, and RNASEL genes were associated with gallbladder cancer risk. Adjustment for multiple comparisons did not materially change these results. Of the 10 genes with multiple SNPs, we inferred halotypes; only one haplotype in the IL8RBgene was associated with gallstones. The haplotype frequency was significantly different between bile dict cancer cases and control (p=0.007). A haplotype comprising 3 SNPs in the IL8RB gene (rs2230054, rs1126579, rs1126580) was associated with a 54% increased risk of bile duct stones (95% CI 1.14-2.07, p=0.02), relative to the most frequent haplotype. In summary, common variants in immune-related genes influencing inflammatory responeses were associated with gallstones and biliary tract cancer, lending further support to the role of inflammation in the pathogenesis of biliary stones and biliary tract cancer. Future larger studies with more complete gene coverage are needed to confirm these results.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.11
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• pp.1621-1628
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• 2015

The immune system plays an important role in maintaining and protecting human health. In the present study, comparison of immuno-modulatory activities between polysaccharides (SFP) and ethanol (SFE) extracts separated from Sargassum fulvellum in macrophages and murine splenocytes were investigated. Immuno-modulatory activities of macrophages were estimated based on cell proliferation, nitric oxide (NO), inducible NO synthase (iNOS), and cytokine production in RAW 264.7 macrophage cells, and lipopolysaccharide was used as a positive control. SFP and SFE treatment did not affect cytotoxicity in RAW 264.7 macrophage cells, and SFP treatment significantly increased NO and cytokine production ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$), whereas SFE did not contribute to the increase in NO and cytokine production. In the case of splenocytes, SFP treatment increased splenocyte proliferation and also highly increased production of Th-1 type cytokines (IL-2 and $IFN-{\gamma}$) than those of SFE. Through this study, we confirmed that immuno-modulatory activities of Sargassum fulvellum may be due to polysaccharide extracts and this can be a potential nutraceutical.

• Journal of the Korean Applied Science and Technology
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• v.35 no.4
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• pp.1003-1012
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• 2018

This study is for checking the possibility of Lentinula edodes as cosmetic materials. For this we carried out biological active evaluation about anti-oxidant and anti-inflammatory effects by Lentinula edodes extracts. We extracted Lentinula edodes with water and 70% ethanol and then in order to evaluate anti-oxidant activity we treated samples by concentrations (100, 500, 1000) ${\mu}g/ml$ and carried out 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, the activity of 2,2'-azino-bis ( 3-ethylbenzothiazoline-6-sulphonic acid )-diammonium salt (ABTS) cation radical scavenging and superoxide dismutase(SOD) like activity. Also, in order to evaluate effect of anti-inflammatory the samples in macrophages(RAW 264.7 cells), we carried out evaluation of cell viability, nitric oxide inhibitory activity western blot. The results of DPPH, $ABTS^+$ radical scavenging activity and SOD-like activity of the Lentinula edodes extracts increased in dose-dependent manner. The cytotoxic of samples by MTT assay showed no toxicity at the concentrations of 10, 25 and $50{\mu}g/ml$ of Lentinula edodes extract. Nitric oxide inhibition activity results showed that the extracts reduced NO productions in a concentration-dependent manner. Expression of inflammatory cytokines as $TNF-{\alpha}$, $PGE_2$ and $IL-1{\beta}$ decreased in a concentration-dependent manner and iNOS and COX-2 proteins expression rates were decreased significantly in western blot analysis. From the results of the experiment, it was comfirmed that the Lentinula edodes extracts had excellent anti-oxidant and anti-inflammatory effect and could be used as a safe natural cosmetic material in the future.

• Nutrition Research and Practice
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• v.10 no.2
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• pp.131-138
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• 2016

BACKGROUND/OBJECTIVES: Citrus and its peels have been used in Asian folk medicine due to abundant flavonoids and usage of citrus peels, which are byproducts from juice and/or jam processing, may be a good strategy. Therefore, the aim of this study was to examine antioxidant and anti-inflammatory effects of bioconversion of Jeju Hallabong tangor (Citrus kiyomi ${\times}$ ponkan; CKP) peels with cytolase (CKP-C) in RAW 264.7 cells. MATERIALS/METHODS: Glycosides of CKP were converted into aglycosides with cytolase treatment. RAW 264.7 cells were pre-treated with 0, 100, or $200{\mu}g/ml$ of citrus peel extracts for 4 h, followed by stimulation with $1{\mu}g/ml$ lipopolysaccharide (LPS) for 8 h. Cell viability, DPPH radical scavenging activity, nitric oxide (NO), and prostagladin $E_2$ ($PGE_2$) production were examined. Real time-PCR and western immunoblotting assay were performed for detection of mRNA and/or protein expression of pro-inflammatory mediators and cytokines, respectively. RESULTS: HPLC analysis showed that treatment of CKP with cytolase resulted in decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycoside forms (naringenin and hesperetin). DPPH scavenging activities were observed in a dose-dependent manner for all of the citrus peel extracts and CKP-C was more potent than intact CKP. All of the citrus peel extracts decreased NO production by inducible nitric oxide synthase (iNOS) activity and $PGE_2$ production by COX-2. Higher dose of CKP and all CKP-C groups significantly decreased mRNA and protein expression of LPS-stimulated iNOS. Only $200{\mu}g/ml$ of CKP-C markedly decreased mRNA and protein expression of cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Both 100 and $200{\mu}g/ml$ of CKP-C notably inhibited mRNA levels of $interleukin-1{\beta}$ ($IL-1{\beta}$) and IL-6, whereas $200{\mu}g/ml$ CKP-C significantly inhibited mRNA levels of $TNF-{\alpha}$. CONCLUSIONS: This result suggests that bioconversion of citrus peels with cytolase may enrich aglycoside flavanones of citrus peels and provide more potent functional food materials for prevention of chronic diseases attributable to oxidation and inflammation by increasing radical scavenging activity and suppressing pro-inflammatory mediators and cytokines.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1576-1584
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• 2013

This study is carried out to assess the relative effects of different doses of dietary glucose or fructose on non-alcoholic fatty liver disease (NAFLD) and hepatic metaflammation in a rodent model of type 2 diabetes. KK/HlJ male mice were fed experimental diets as follows: 1) control (CON), 2) moderate glucose (MG, 30% of total calories as glucose), 3) high glucose (HG, 60% of total calories as glucose), 4) moderate fructose (MF, 30% of total calories as fructose), and 5) high fructose (HF, 60% of total calories as fructose) for three weeks. Food intake was not affected by treatments. Compared with HF, HG not only increased serum fasting glucose and area under the curve during oral glucose tolerance test, but also decreased the levels of serum insulin and adiponectin. It indicated that glucose control was complicated via high glucose intake. High fructose treatment led to increased triglyceride in the serum and liver. In comparison to HG, high fructose diet activated NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome consisting of apoptosis-associated speck-like protein containing a CARD (ASC), NLRP3 and caspase 1, which increases interleukin (IL)-$1{\beta}$ maturation and secretion. The activation of NLRP3 inflammasome was accompanied by increased levels of tumor necrosis factor alpha (TNF-${\alpha}$) and IL-6. However, the expression of NLRP3 inflammasome components and pro-inflammatory cytokines did not differ between CON and HG. These data suggested that dietary fructose triggers hepatic metaflammation accompanied by NLRP3 inflammasome activation and has deleterious effects on NAFLD.

• Journal of the Korean Institute of Oriental Medical Informatics
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• v.15 no.1
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• pp.57-66
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• 2009

Objectives : The aim of the present study is to evaluate the wound healing-enhancing and anti-inflammatory effects of Pinus densiflora, Cornus officinalis, Zingiber officinale, Ganoderma japonicum and Scutellaria baikalensison human keratinocyte, HaCaT cells. Methods : We adopted in vitro wound healing assay to measure the proliferation-and migration-enhancing effects in HaCaT cells. The expressions of cytokine genes were measured in HaCaT cells using real-time PCR analysis. Results : The extracts of Pinus densiflora, Cornus officinalis, Zingiber officinale, Ganoderma japonicum and Scutellaria baikalensis enhanced the proliferation and migration of HaCaTcells. The expression of keratinocyte growth factor receptor(FGFR2-IIIb) gene was also induced. The extracts inhibited iNOS, IL-$1{\beta}$ and TNF-$\alpha$ gene expression. Conclusions : The extract of Pinus densiflora, Cornus officinalis, Zingiber officinale, Ganoderma japonicum and Scutellaria baikalensis has wound healing-enhancing effects and anti-inflammatory effects.

• Journal of Periodontal and Implant Science
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• v.23 no.1
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• pp.145-158
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• 1993

The oral microbiota such as P. gingivalis, P. intermedia and A. actinomycetemcomitans play a primary role in the initiation and progression of the periodontal disease. The purpose of this study was to evaluate the antimicrobial effects and inhibitory effects of honokiol and magnolol on the bacterial collagenase activity, cytotoxicity and cytokine production of periodontopathic microorganisms. The antimicrobial activities of honokiol and magnolol was evaluted with minimum inhibition concentration. Honokiol was more active than magnolol, but less than chlorhexidine on antimicrobial activity. The inhibitory effects of magnolol and honokiol on the collagenolytic activity and cytotoxicity were evaluated using a Collagenokit CLN-100 and rapid colorimetric assay (MTT method) for cellular growth and survival of gingival fibroblast and periodontalligament cell and $[^3H]-thymidine$ incorporation for the gingival epithelial cell. The inhibitory effects on the collagenolytic activity was the highest in chlorhexidine, and the lowest in magnolol. Magnolol had the lowest cytotoxic effect and chlorhexidine had the highest. The inhibitory effects on cytokine production was evaluated using $interleukin-1{\beta}$ ELISA kit (Cistron Biotech.), IL-6, $TNF-{\alpha}$ ELISA kit (Genzyme) and inhibitory effects were higher than bacterial LPS and there is no difference among the honokiol, magnolol and chlorhexidine. From these results, the antimicrobial and antienzymatic activities of honokiol and magnolol were seemed to inhibit bacterial growth and enzyme activities with lesser cytotoxic activities. Therefore, it was suggested that honokiol and magnolol are very effective antimicrobial agents on periodontal pathogens.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.535-544
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• 2017

Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol ($0.05{\mu}g/cm^2$) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of $TNF-{\alpha}$, $IL-1{\beta}$, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.

• The Journal of Korean Medicine
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• v.32 no.2
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• pp.63-78
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• 2011

Objective: This study aimed to evaluate the protective effects of Maekmundong-tang (MMDT) on an elastase-induced COPD model. Materials and Methods: The extract of MMDT was treated to A549 cells and elastase-induced COPD mice model. Then, various parameters such as cell-based cytoprotective activity and histopathological findings were analyzed. Results: MMDT showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, protein level of Cdk1, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. MMDT treatment also revealed a protective effect on the elastase-induced COPD mice model. This effect was evidenced via histopathological finding including immunofluorescence stains against elastin, collagen, and caspase 3, and protein level of Cdc2 in lung tissue. Conclusion: These data suggest that MMDT has pharmaceutical properties on COPD. This study can provide scientific evidence for the efficacy of MMDT for clinical application to patients with COPD.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.10-16
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• 2014

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$ and TNF-${\alpha}$. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.