• Journal of Pharmacopuncture
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• v.13 no.3
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• pp.63-71
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• 2010

Objectives: Gallic acid (GA) is the major component of tannin which could be easily founded in various natural materials such as green tea, red tea, grape juice, and Corni Fructus. The purpose of this study is to investigate the effect of Gallic acid (GA) on production of interleukin (IL) in mouse macrophage Raw 264.7 cells stimulated by lipopolysaccharide (LPS). Methods: Productions of interleukins were measured by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$ (multi-analyte profiling beads) technology. Firstly, cell culture supernatant was obtained after treatment with LPS and GA for 24 hour. Then, it was incubated with the antibody-conjugated beads for 30 minutes. And detection antibody was added and incubated for 30 minutes. And Strepavidin-conjugated Phycoerythrin (SAPE) was added. After incubation for 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System and concentration of interleukin was determined. Results: The results of the experiment are as follows. 1. GA significantly inhibited the production of IL-3, IL-10, IL-12p40, and IL-17 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 25, 50, 100, 200 uM (p<0.05). 2. GA significantly inhibited the production of IL-6 in LPS-induced mouse macrophage RAW 264.7 cells at the concentration of 50, 100, 200 uM (p<0.05). 3. GA diminished the production of some cytokine such as IL-4, IL-5, and IL-13 in LPS-induced mouse macrophage RAW 264.7 cells. 4. GA did not show the inhibitory effect on the production of IL-$1{\alpha}$ and IL-9 in LPS-induced mouse macrophage RAW 264.7 cells. Conclusions: These results suggest that GA has anti-inflammatory activity related with its inhibitory effects on the production of interleukins such as IL-3, IL-10, IL-12p40, IL-17, and IL-6 in LPS-induced macrophages.

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.306-311
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• 2003

Soy, high dietary intake for the oriental population, is a main source of isoflavonoids. Sophoricoside (SOP) an isoflavone glycoside was isolated from immature fruits of Sophora japonica (Leguminosae family) and its inhibitory effect on chemical mediators involved in inflammatory response was investigated in this study. SOP inhibited the interleukin (IL)-6 bioactivity with an $IC_{50}$ value of 6.1 $\mu$M whereas it had no effects on IL-1$\beta$ and TNF-a bioactivities. SOP was identified as a selective inhibitor of cyclooxygenase (COX)-2 activity with an $IC_{50}$ value of 4.4 $\mu$ M, but did not show inhibitory effect on the synthesis of COX-2. However, SOP had no effect on the production of reactive oxygen species including superoxide anions and nitric oxide. These results revealed that in vitro anti-inflammatory action of SOP is significantly different from that of genistein known as a phytoestrogen of soy products. This experimental study has documented an importance of dietary soy isoflavonoids as multifunctional agents beneficial to human health, and will help to clarify protective mechanisms of SOP against inflammatory conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8775-8778
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• 2014

Background: To explore the relationship between polymorphisms of interleukin17 (IL-17) gene(A-832G 7488A/G) and the susceptibility to silicosis, a risk factor for lung cancer. Materials and Methods: A total of 113 silicosis patients and 116 workers without silicosis were enrolled in the case-control study. IL-17A A-832G and IL-17F 7488A/G polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of AA,GG and AG of IL-17A A-832G locus in the case and control groups were 46.9%, 8.0%, 45.1%, and 49.2%, 7.6%, 43.2%, respectively, with no significant differences (p>0.05).The GG genotype in the IL-17F (7488A/G) locus was not found. The frequencies of AA and GA of IL-17F 7488A/G locus in the case and control groups were 84.1%, 15.9% and 66.4%, 33.6%, respectively (p<0.05). Analysis of combined effects showed that the individuals with GG+AG genotype of IL-17A and GG+GA genotype of IL-17F are protected against silicosis (OR=0.469). Conclusions: IL-17F 7488A/G is associated with susceptibility to silicosis, and G allele may have a protective effect. No relationship was found between IL-17A gene polymorphisms at A-832G and silicosis.

• BMB Reports
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• v.44 no.5
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• pp.335-340
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• 2011

In this study, we attempted to isolate novel mast cell-stimulating molecules from Staphylococcus aureus. Water-soluble extract of S. aureus cell lysate strongly induced human interleukin-8 in human mast cell line-1 and mouse interleukin-6 in mouse bone marrow-derived mast cells. The active molecule was purified to homogeneity through a $C_{18}$ reverse phase HPLC column. By determination of its structure by MALDITOF and $^1H$- and $^{13}C$-NMR, adenosine was revealed to be responsible for the observed cytokine induction activities. Further studies using 8-sulfophenyl theophylline, a selective adenosine receptor blocker, verified that purified adenosine can induce interleukin-8 production via adenosine receptors on mast cells. Moreover, adenosine was purified from S. aureus-engulfed RAW264.7 cells, a murine macrophage cell line, used to induce phagocytosis of S. aureus. These results show a novel view of the source of exogenous adenosine in vivo and provide a mechanistic link between inflammatory disease and bacterial infection.

• Journal of the Korean Applied Science and Technology
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• v.35 no.2
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• pp.509-518
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• 2018

The purpose of this study was myokine product and role with physical activity and literature review. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular disease, colon cancer, dementia and even depression. And myokine has been regarded an important factor of exercise training and brain growth factor for the prevention of Alzheimier's disease. During exercise the release of anti-inflammatory myokine from contracting muscle controled the metabolic response, and IL-4, IL-6, IL-7, IL-10, and IL-15 controled muscle hypertrophy, myogenesis and angiogenenesis. IL-6 promoted the lipid metabolism through AMPK activation. IL-1Ra, IL-10 and sTNF-R inhibited $TNF-{\alpha}$ as the pro-inflammatory cytokine. IL-15 increased the releasing volume from contracting muscle, and promoted the anabolic factor of muscle growth. IL-7 and IL-8 activated the angiogenesis through the more activation of C-X-C receptor signal transmission.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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• pp.670-677
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• 2020

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P_app; 9.7×10^-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t_1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C_max after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.969-976
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• 2006

Novel chalcones were found as potent inhibitors of interleukin-5 (II-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at $50\;{\mu}M,\;IC_{50}=25.3\;{\mu}M$) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c ($IC_{50}=12.6\;{\mu}M$), 2d ($IC_{50}=12.2\;{\mu}M$), and 2i ($IC_{50}=12.3\;{\mu}M$) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.

• Korean Journal of Medicinal Crop Science
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• v.27 no.1
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• pp.38-44
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• 2019

Background: Taraxacum platycarpum has been used in traditional medicine in Korea to treat intoxication and edema and as a diuretic. According to previous reports, it has anti-cancer, anti-gastritis, and anti-inflammation effects. However, the improvement effect of T. platycarpum on rheumatoid arthritis has not been investigated. The anti-oxidative and anti-inflammation effects of the aerial parts of T. platycarpum are different from those of its subterranean parts. Thus, we evaluated the effect of the water extracts of Taraxaci radix (WTR) on type II collagen-induced rheumatoid arthritis (CIA) in animal models. Methods and Results: Rheumatoid arthritis was induced by type II collagen. WTR (100 mg/kg and 500 mg/kg) was administered to the animal models. Methotrexate was used as the positive control. The levels of interleukin-6, TNF-alpha, and type II collagen IgG in the animals were measured by using enzyme-linked immunosorbent assay. Treatment with 500 mg/kg WTR decreased the serum levels of interleukin-6, TNF-alpha, and collagen IgG in the CIA models. Moreover, treatment with WTR diminished the arthritisinduced swelling of the hind legs and monocyte infiltration in the bloodvessels of the animal models. Conclusions: These results indicate that WTR has the potential to improve rheumatoid arthritis by reducing the levels of inflammatory cytokines such as interleukin-6 and TNF-alpha. However, further experiments are required to elucidate the influence of WTR on signal transduction in vitro and in vivo.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.1
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• pp.34-47
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• 2021

Objectives: This study was designed to examine anti-inflammatory effect and mechanism of Citri Reticulatae Viride Pericarpium water extract (CRE). Methods: Cell cytotoxicity was tested with RAW 264.7 cells. To investigate anti-inflammatory effect of CRE in lipopolysaccharide (LPS)-induced RAW 264.7 cell, we measured nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). In addition, mitrogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) were examined by western blotting in LPS-induced RAW 264.7 cell with treated CRE. Results: In cytotoxicity analysis, CRE does not affect cell cytotoxicity. As compared with the control group, the expression of NO, PGE2, TNF-α, IL-6 were significantly decreased, and IL-10 was significantly increased in LPS-induced RAW 264.7 cell with treated CRE. As a result of Western blotting, there was concentration-dependent inhibition of pp38, pERK in MAPK pathway and significant reduction of pp65 in the NF-κB pathway. Conclusions: CRE might have anti-inflammatory effect in LPS-induced macrophages by promoting the production of IL-10.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.348-353
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• 2005

In this paper we discuss the formulation and the analysis of a signaling pathway by Petri nets. In order to explicitly and formally describe the molecular mechanisms and pathological characteristics of signaling pathways, we propose a new modeling method to construct signaling pathways on the basis of formal representation of Petri net. Our proposed extended algorithm effectively finds basic enzymic components of signaling pathways by employing T-invariants of Petri nets with considering the origination leading to an occurrence of inhibition functions than existing methods. An application of the proposed algorithm is given with the example of Interleukin-1 and Interleukin-6 signaling pathways.