• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.414-419
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• 2006

Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of inflammation and osteoarthritis. And nitric oxide (NO) activated the MMPs responsible for PG degradation in articular chondrocytes. Therefore, we have studied the effects on anti-inflammation and analgesic by ethyl acetate fraction from 70% ethanol extract of Perilla Frutescens (EPF). EPF inhibited LPS plus inflammation-cytokines-induced proteoglycan (PG) degradation, matrix-metalloproteinase (MMP-2,9) expression in rabbit articular chondrocytes. Also, EPF have inhibitory effects on LPS or LPS plus inflammation cytokines-induced nitric oxide (NO) and PGE2 production in mouse macrophage andrabbit articular chondrocytes. These results suggest that EPF decreases PGE2, iNOS, MMPs activity and PG degradation in mouse macrophage and/or rabbit articular chondrocytes. In vivo, EPF was shown to have inhibitory effects on acetic acid-induced pain. The herbal extract with this profile, may have utility in the treatment of osteoarthritis.

• Journal of Microbiology and Biotechnology
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• v.20 no.11
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• pp.1585-1591
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• 2010

A comprehensive study on the production of inflammatory mediators in the lungs of BALB/c mice following infection with Stenotrophomonas maltophilia was conducted. The levels of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-${\alpha}$), and interleukin-1${\beta}$ (IL-1${\beta}$) were raised in the lungs of infected mice compared with control. The production of anti-inflammatory cytokine IL-10 was slightly delayed. Its peak level was on the $2^{nd}$ day, whereas the peak of pro-inflammatory cytokines was observed on day 1 after intranasal challenge. This was accompanied by a rise in myeloperoxidase (MPO) and malondialdehyde (MDA) on day 1. The increase in MPO levels matched with histopathological observations, as neutrophils infiltration was detected on the first day. Alveolar macrophages (AMs) obtained from infected animals showed a higher rate of uptake and killing when exposed to bacteria in vitro, compared with similar experiments conducted with AMs from normal mice (control). This suggests that AMs were more efficient in cleaning the bacteria. The nitric oxide (NO) production however started early during infection but reached its maximum on the $3^{rd}$ day. No mortality was observed among the infected animals, and infection was resolved by the $5^{th}$ day post infection. No drastic changes in the lung tissue were observed on histopathological examination.

• International Journal of Oral Biology
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• v.31 no.2
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• pp.67-72
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• 2006

Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of $30{\mu}M$ SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration($3{\mu}M$) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1491-1498
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• 2007

NC/Nga mice with contact dermatitis induced using DNCB were applied with GJHB(祛風燥濕解毒方), and its influence on the expressions of IgE, immune related cytokines, and immunoglobulins were tested. The results were obtained as follows ; GJHB significantly redued the production of IgE compared to the control. GJHB significantly reduced the amount of IL-4 within the suspension of spleen cells, but significantly induced the production of $IFN-{\gamma}$, compared to the control. GJHB significantly reduced the production of IL-6 and $TNF-{\alpha}$ in the serum compared to the control. GJHB significantly suppressed the concentration of IgM, IgG2a, IgG2b in the serum. However, no significant decrease of IgG1 was observed. From the results above, GJHB suppressed the intermediate factors during the hypersensitive immune response as well as suppressing the generation of inflammation related cytokines. Therefore, anti-allergic effect of GJHB on the contact dermatitis through immune modulation was confirmed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1101-1111
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• 2003

Our study shows that EC extract has inhibitory effect on pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, iNOS and COX2 in hFLSs. IL-1β, IL-6, iNOS and COX2 mRNA expression is suppressed at a low dasage (1㎍/ml) of EC extract. TNF-α was also suppressed at higher dosages (10 ㎍/ml, 100㎍/ml). EC extract also inhibited TNF-α, IL-1β and IL-6 production in pro-inflammatory cytokine stimulated-hFLSs. Expecially IL-1β(p<0.05) production are suppressed significantly. On the other hand, EC extract did not show any cytotoxicity. Thses data suggest that EC extract has anti-inflammatory effect mostly by inhibiting IL-1β production, and thus could be used to prevent or treat some inflammatory disease such as RA. It remains to be known what are the major components responsible for anti-inflammatory effect and what is the main mechanism.

• Food Science and Preservation
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• v.30 no.1
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• pp.65-77
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• 2023

In this study, we investigated the immunological properties of six strains of Acetobacter pasteurianus through nuclear factor-kappa B/activator protein-1 (NF-κB/AP-1) transcription factor activation and nitric oxide (NO) and cytokine production in macrophages. We found that the six A. pasteurianus strains had no significant inhibitory effect on the cell viability of RAW-Blue^TM cells at the concentration of (25, 50, 100 CFU/macrophage). The production of NO and cytokines (TNF-α, IL-1β, and IL-6) showed different abilities of immune activation for each strain, and it was 0.7 to 0.9 times higher than that of the LPS (100 ng/mL, v/v) positive control and 7 to 8 times superior to that of the negative control group. To explore the underlying mechanism, we evaluated the mRNA expression of pro-inflammatory genes. Consequently, we found that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression including genes expression of cytokines were elevated by the six A. pasteurianus treatment. These results suggested that the six strains of A. pasteurianus have an excellent industrial application value as a functional material for the purpose of enhancing immune function.

• Journal of Life Science
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• v.17 no.10
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• pp.1354-1360
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• 2007

Theaflavins (TF) and thearubigins (TR) are constituents of tea pigments which are polyphenols derived from Korean fermentation tea. After TF, TR and [(-) epigallocatechin-3-gallate](EGCG) have been applied to macrophage cell line (RAW264.7) nitric oxide (NO) synthesis and cytokines production were estimated. Cytokines production by enzyme linked immune-sorbent assay (ELISA) determined. NO production was increased by about 1.5-folds at the dose of $80\;{\mu}g/ml$ compared to control and lipopolysaccharide (LPS) stimulation when TF, TR and EGCG were applied to a RAW264.7 cell. Interleukin-6 (IL-6), Tumor necrosis factor ($TNF-{\alpha}$) and granulocyte-macrophage colony stimulating factor (GM-CSF) increased depended on concentrations of TF, TR and EGCG. The production of tumor necrosis $factor-{\alpha}$ increased highly in TR, TF and EGCG group with LPS. These results suggest that TF, TR and EGCG have immune-enhancement effect through the cytokine production. TF, TR and EGCG inhibited cancer cell viability, the anticancer effect of these polyphenols may explain the anti-tumor promotion action and antioxidant activity of these tea constituents.

• Analytical Science and Technology
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• v.28 no.4
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• pp.260-269
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• 2015

The protective effects of extract powder of Angelica gigas on the degeneration of the articular cartilage in rats was investigated with monosodium iodoacetate (MIA)-induced osteoarthritis, The treatment of high concentration (50 μg/mL) of Angelica gigas effectively inhibited nitric oxide (NO) production induced by interleukin-1α (IL-1α) without any cytotoxicity. Specifically, mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were dose dependently reduced by extract powder of Angelica gigas. Importantly, mRNA expression in articular cartilage of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were clearly reduced. The inflammatory cytokines in blood were also reduced as well. These results suggested that the protective effects on the degeneration of the articular cartilage was derived from the inhibitory effects of mRNA and protein expression of tested inflammatory cytokines which is linked to prevent the degradation of proteoglycan (PG), the main matrix content in articular cartilage. Meanwhile, the 2 hrs incubation of decursin, a major compound of extract powder in rat whole blood rapidely converted decursin into decursinol which shows string anti-inflammatory activity. The coverted decursinol was detected after 8 hrs in whole blood by LC-MS/MS. Conclusively, the inhibitory effects of inflammatory cytokines production in osteoarthritis may be derived from the production of decursinol, which performs against inflammatroy cytokines like TNF-α, IL-1β, and IL-6.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.829-836
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• 2003

Seogakjihwang-tang (SJT) was widely used to treat patients suffering from cerebral infarction. But scientific investigation has been carried out very little. The aim of the present study is to investigate the effect of SJT on the production of various cytokines in the patients with cerebral infarction (CI). We investigated interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-1 in the sera of 27 patients with cerebral infarction under consciousness disorders and 10 normal controls using an originally devised sensitive sandwich enzyme-linked immunosorbent assay (ELISA). We found that plasma levels of IL-4 were slightly elevated in patients with cerebral infarction, whereas plasma levels of IL-10 (P<0.001) and TGF-1 were reduced. Peripheral blood mononuclear cells (PBMC) obtained from the patient with CI were cultured for 24 h in the presence or absence of lipopolysaccharide (LPS) or phytohaemagglutinin (PHA). The amount of IL-4, IL-10 and TGF-1, in culture supernatant, was significantly increased in the LPS or PHA treated cells compared to unstimulated cells (P<0.05), We also show that increased cytokines IL-4, and IL-10 level was significantly inhibited by SJT in a dose-dependent manner. Maximal inhibition rate of IL-4 and IL-10 production by SJT was 45.63.3% and 614.7% for LPS-stimulated cell and 27.31.2% and 83.62% for PHA-stimulated cells, respectively (P<0.05). On the other hand, SJT significantly increased the LPS or PHA-induced TGF-1 production (P<0.05). These data suggest that SJT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of CI.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.