• Journal of Haehwa Medicine
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• v.24 no.2
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• pp.35-57
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• 2016

Objectives : The purpose of this study is to prove the effect and mechanism of Gamikyejakjimogawusul-tang(GKHA) herbal acupuncture on induced rheumatoid arthritis model of DBA/1 mice. Methods : We check effect of GKHA extract on the AST, ALT, Creatinine, BUN of serum and cell viability of GK extract in RAW 264.7 cells to test the stability of this study. In vitro, we measure total phenol contents, total flavonoid contents, DPPH free radical scavenging activity, ABTS cation radical scavenging activity of Gamikyejakjimogawusul-tang, effect of GK extract on ROS(Reactive Ooxygen Species) production to estimate a anti-oxidant capacity, and we also measure effect of GK extract on NO (Nitric Oxid), IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF production in RAW 264.7 cells to estimate a anti-inflammatory efficacy. In vivo, we compare a rheumatoid arthritis manifestation between control and experimental group and estimate a AI. Then we check effect of GKHA on the level of WBC, neutrophil, lympocyte, monocyte in the blood to see the effect of immune cells in blood. In addition we measure effect of GKHA on the level of hs-CRP, IgM, IgG, IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF in serum. We observe effects of GKHA on imaging of cartilage degeneration using micro CT-arthrography in paw hind. And we calculate effects of GKHA that reduced BV ratio, BS/BV ratio using 3D Micro-CT. Lastly we observe effects of GKHA histopathologic examination analysis. Results : 1. The toxicity on liver and kidney was disregardable and the cytotoxicity against RAW 264.7 cells was also disregardable. 1. Total phenol contents and total flavonoid contents in GK extract were in high level. 2. DPPH free radical scavenging activity and ABTS cation radical scavenging activity were increased according to concentration of GK extract 3. ROS production was significantly decreased in GK extract (at 10, $100{\mu}g/ml$). 4. NO, IL-6, TNF-${\alpha}$, MCP-1 production were significantly decreased in GK extract(at 10, $100{\mu}g/ml$). IL-17, GM-CSF production were significantly decreased in GK extract(at 1, 10, $100{\mu}g/ml$). IL-$1{\beta}$, IL-21 production were also decreased but there was no statistical significance. 5. 25x observation after H&E and M-T staining, infiltration of immune cells and subsidence of the cartilage and damage to the synovial cells were decreased. Conclusions : This study showed that GKHA extract had anti-oxidant capacity, anti-inflammatory efficacy. GKHA extract also had inhibiting effect on the process of rheumatoid arthritis and can protect joint and cartilage. So we expect that GKHA extract can be a meaningful treatment to rheumatoid arthritis patients.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.2
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• pp.76-96
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• 2008

Purpose: This study was performed to evaluate anti-inflammatory effects of Jogantanggagambang(JGTG). Methods: In the study of anti-oxidant activities, JGTG was investigated by DPPH radical scavenger activity, superoxide dismutase activity and superoxide anion radical scavenger activity. In the study of anti-inflammatory effects, JGTG was investigated using cultured cells and murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were measured in mouse lung fibroblast cells(mLFCs) and RAW264.7 cells. Results: 1. JGTG showed a safety in cytotoxicity and toxicity of liver. 2. JGTG effected scavenging activity on DPPH free radical, superoxide dismutase and superoxide anion radical. 3. JGTG in RAW 264.7 cell decreased IL-$1{\beta}$ mRNA expression, IL-6 mRNA expression, TNF-${\alpha}$ mRNA expression at 50, $100{\mu}g/m{\ell}$ and also decreased NOS-II mRNA expression at $100{\mu}g/m{\ell}$, and decreased COX-2 mRNA expression at 10, 50, $100{\mu}g/m{\ell}$. 4. JGTG in RAW 264.7 cell decreased significantly IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ at 50, $100{\mu}g/m{\ell}$. 5. JGTG inhibited significantly IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ production in serum of acute inflammation-induced mice. 6. JGTG decreased significantly IL-$1{\beta}$ mRNA production in spleen tissue. Conclusion: These results suggest that JGTG can be used for treating diverse female diseases caused by inflammation

• The Korea Journal of Herbology
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• v.20 no.4
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• pp.141-149
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• 2005

In order to investigate the immunomodulational effects of Lonicerae Caulis et Folium, the author measured cytokines production(IL-10, IL-12(P35), IL12(P40), $IFN-{\gamma}$) in mice splenocytes. The results were obtained as follows : 1. The water extract of Lonicerae Caulis et Folium significantly enhanced the gene expression of IL-12(P35), IL-12(P40), but reduced the gene expression of IL-10, $IFN-{\gamma}$. 2. In water fraction and ethyl acetate fraction, the gene expression of IL-12(P35), $IFN-{\gamma}$ was significantly increased and that of IL-12(P40), IL-10 was decreased. The above results demonstrate that Lonicerae Caulis et Folium has enhancing immune activity by upregulation of these cytokines. Therefore, if we make the relationship between these cytokines(IL-10, IL-12, $IFN-{\gamma}$) besides IL-1, IL-4, IL-6, $TNF-{\alpha}$, IL-8, $TGF-{\beta}$ and so on which concerned the immunopotentiation, the immunopotentiational mechanism of Lonicerae Caulis et Folium will be shown clearly.

• Advances in Traditional Medicine
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• v.2 no.1
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• pp.41-46
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• 2002

In our study, the several cytokines were determined in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Adamantiades-Behcets patients. Adamantiades-Behcets disease (ABD) is a systemic inflammatory disorder and might involve immune dysfunction. High levels of $TNF-\alpha,\;IL-1\beta$ and $IFN-{\gamma}$ indicate the activation of inflammatory reactions and immune system in ABD. Gami-Phedoc-San (GPS) is an Oriental herbal medication, which has been used in Korea for the treatment of ABD. GPS (1 mg/ ml) significantly inhibited the secretion of proinflammatory cytokines, $TNF-\alpha\;and\;IL-1\beta$, compared to absence of GPS (by $50.5{\pm}1.9%$ inhibition for $TNF-\alpha$ and $106.9{\pm}16.8%$ for $IL-1\beta$). GPS also inhibited the production of $IFN-\gamma$, immunoregulatory Th1 cytokine, by $78.4{\pm}2.8%$. The inhibitory effects of GPS on cytokine secretion showed dose-dependent manner, and the pre-treatment of 1 mg/ml GPS had better effects than immunosuppressive drug for treatment of ABD, cyclosporin A. Our results suggest that GPS treatment for ABD patients might have pharmacological activity of immune and inflammatory responses through the cytokine modulation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.121-141
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• 2011

Objective : This Experimental study was done to investigate the Effect of Taklisodok-um and Hwangryunhaedok-tang(TH) on Atopic Dermatitis. Methods : We assessed effects of TH on the IgE, IL-4, IL-5, IL-6, IgM, IgG1, IFN-${\gamma}$ in vivo, on the IL-4, IL-5, CCR3 in the skin tissues of ear and dorsum with NC/Nga mice. And we assessed effects of TH on the COX-2, IL-$1{\beta}$, TNF-${\alpha}$, IL-6 with RAW 264.7 cell. Results and Conclusion : 1. IgE, IL-4, IL-5, IL-6, IgM, IgGl levels in the serum of TH treated NC/Nga mouse group were decreased compared to the untreated control mice. IFN-r showed a increase in the experimental group compared to the untreated control group. The spleen weight of TH treated NC/Nga mice was decreased compared to the untreated control group. 2. mRNA expression levels of IL-4, IL-5 and CCR3 in the skin tissues of TH treated NC/Nga mice were decreased, and expression levels of IL-6 in the skin tissues of TH treated NC/Nga mice were decreased compared to the untreated control group. IFN-${\gamma}$ mRNA expression levels were increased compared to the untreated control group. 3. Judged from that IL-$1{\beta}$, TNF-${\alpha}$, IL-6 express of gene, effect of inflammatory Cytokines revelation were decreased compared to the untreated control group. 4. Depend on the strength of TH, inflammatory RAW 264.7 in the serum of TH were inhibited compared to the untreated control serum that leaded a COX-2 activity model. 5. Histological observation of the ear and skin tissues showed that the extents of inflammation and infiltrated immune cells in the epidermis and dermis of TH treated NC/Nga mice were highly reduced compared to the untreated control group.

• Natural Product Sciences
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• v.21 no.4
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• pp.268-272
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• 2015

Sesquiterpene-quinone is a class of secondary metabolites frequently encountered from marine sponge. The present study was designed to examine the anti-inflammatory action of sponge-derived dactyloquinone B (DQB) and cyclospongiaquinone-1 (CSQ1) mixture using lipopolysaccharide (LPS)-induced inflammatory responses. We measured the production of nitric oxide (NO), tumor necrosis factor-alpha ($TNF-{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), and interleukin-6 (IL-6) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 production, which increased by treatment with LPS, were significantly inhibited by DQB and CSQ1 mixture. It also decreased the production of NO production, and iNOS and COX-2 expression. Furthermore, it reduced 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema of ICR mice. These results demonstrate that sesquiterpene-quinone, DQB and CSQ1 mixture, might serve as a chemical pipeline for the development of anti-inflammatory agent.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.898-908
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• 2000

Background : Eotaxin a CC chemokine specific for eosinophils, is implicated in the pathogenesis of asthma by recruiting eosinophils into the airways. Theophylline has been used for the treatment of asthma and recently was proposed to have an anti-inflammatory action. The aim of this study is to examine whether theophylline may inhibit the eosinophilic airway inflammation by reducing the expression of eotaxin. Methods : The expression of eotaxin mRNA was assessed by Northern analysis in A549 cells 4 h after stimulation with TNF-$\alpha$ or IL-1$\beta$. And then, theophylline was added to A549 cells stimulated with 0.1 ng/mL IL-1$\beta$. Results : Eotaxin mRNA expression rates induced by 0.1, 1, 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 7%, 22%. 28%, respectively. Eotaxin mRNA expression rates induced by 0.01, 0.1, 1, 10 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 10%, 42%, 63%, 72%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 27%, 18%, 8%, respectively. Eotaxin mRNA expression rate after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 0.1 ng/mL IL-1$\beta$ as compared with $\beta$-actin, were 43%, 47%, 12%, 8%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1, 1, 10 mM theophylline induced by 0.1 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 48%, 40%, 33%, 22%, 16%, 14%, respectively. Conclusion : These results suggest that theophylline may reduce eosinophil infiltration of the airway at least in part by reducing the expression of eotaxin under the conditions of these experiments.

• Journal of Embryo Transfer
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• v.31 no.4
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• pp.323-333
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• 2016

Pro-inflammatory cytokines, interleukin-$1{\beta}$(IL1B), IL6, and tumor necrosis factor-alpha (TNF), are known to play important roles in regulating the endometrial function in the uterus during the estrous cycle and pregnancy in several species. However, the expression and function of these cytokines and their receptors in the uterine endometrium during the estrous cycle have not been studied in pigs. Thus, this study determined the expression and regulation of IL1B, IL6, TNF and their respective receptors, IL1R1, IL1RAP, IL6R, GP130, TNFRSF1A, and TNFRSF1B during the estrous cycle in pigs. To analyze levels of each gene expression in the uterine endometrium we obtained from endometrial tissues on Days 0, 3, 6, 9, 12, 15, and 18 of the estrous cycle. Real-time RT-PCR analysis showed that levels of IL1B, IL1RAP, IL6R, GP130, TNF, TNFRSF1A, and TNFRSF1B mRNAs were highest on Day 15 or 18 of the estrous cycle, which corresponds to the proestrus period. Levels of IL1R1 were highest on Day 0, while levels of IL6 were biphasic with high levels on Day 6 and Day 15. The abundance of IL1B, IL6, IL6R, and TNF mRNAs was decreased by progesterone, while levels of GP130 were increased by progesterone in endometrial tissue explants. These results showed that expression of pro-inflammatory cytokines and their receptors changed stage-specifically during the estrous cycle and regulated by progesterone in the uterine endometrium in pigs, suggesting that these pro-inflammatory cytokines may be involved in the regulation endometrial function during the estrous cycle in pigs.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.3
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• pp.18-32
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• 2013

Objectives: In this research, the effect of Gyogam-dan (GGD) on depression and immunity were assessed in ovariectomized rats subjected to repetitive stress. GGD is the prescription consisting of Poria cocos and Cyperi Rhizoma. Methods: Ovariectomized rats were repeatedly stressed over a 2-week period. After GGD (100 or 400 mg/kg) were orally administered, Elevated Plus Maze (EPM) and forced swimming test (FST) were performed to evaluate depressive and anxiety response. As well, the change of corticosterone (CORT) and the change of interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-4 (IL-4) in blood serum and in brain were mesured. Results: 1. In the EPM, there were no statistically significant differences among the groups. 2. In the FST, immobility time significantly decreased in rats of each experiment group compared with the control group (p<0.01). 3. Serum CORT level were decreased in 400 mg GGD group (p<0.05). 4. On IL-$1{\beta}$ and IL-4 measurement in the serum and brain, there were not significant increase or decrease compared with the control group. Conclusions: These results suggest that GGD is effective to reduce depression-behavior in ovariectomized rats. However, GGD do not has significant efficacy to reduce anxiety-behavior in EPM test. Measurement of serum CORT level reveals significant decrease and it shows anti-depressant like effect. Results on immunity are not significant.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1063-1072
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• 2009

Membranous nephropathy(MN) is the most common cause of adult nephrotic syndrome worldwide. But treatment of MN is not defined. This study was to evaluate the effects of Lonicerae Flos Extract(LFE) on the MN induced by cBSA in mice. Mice were divided into 4 groups. The first group named for 'Normal' was injected with a saline solution. The second group named 'Control' treated with cBSA(10 mg/kg i.p) only. The third group named 'LFE-250', treated with cBSA(10 mg/kg i.p) and LFE(250 mg/kg, p.o). The fourth group named 'LFE-500'treated with cBSA(10 mg/kg i.p) and LFE(500 mg/kg, p.o). After cBSA and LFE treatment for 4 weeks, we measured change of body weight, 24hrs proteinuria, serum albumin, total cholesterol, triglyceride, BUN, creatinine, TNF-$\alpha$, IL-6, IL-$1{\beta}$, IL-10, IFN-$\gamma$, IgA, IgM and IgG levels. The morphologic changes of renal glomeruli were also observed with a light microscope. The levels of 24 hrs proteinuria, total cholesterol, IgG , IgM, IgA, IL-6 were significantly decreased in both LFE groups. The level of triglyceride, IL-$1{\beta}$ was significantly decreased in LFE-500 group. The level of Albumin was significantly increased in LFE-250 group. The level of TNF-$\alpha$, IFN-$\gamma$ were significantly decreased in LFE-250 group. The mRNA expression of IL-$1{\beta}$ in splenocytes was consideraly decreased in LFE-500 group. In histological findings of kidney tissue, thickening of GBM decreased in both LFE groups. This study shows that the LFE might be effective for treatment of MN. More clinical data and studies are to be done for efficient application.