• 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.

• The Journal of Korean Medicine
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• v.30 no.2
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• pp.17-29
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• 2009

Objectives: The present study is focused on the inhibitory effect of the rhizome hexane fraction extract of Zingiberis Rhizoma Crudus (ginger hexan extract; GHE) on the production of inflammatory mediators such as NO, $PGE_2$, and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV2 cells, a mouse microglial cell line. Methods: We separated the hexane fraction from Zingiberis Rhizoma Crudus's methanol extract. The inhibitory and anti-inflammatory effect of GHE was examined on microglial activation. Results: GHE significantly inhibited the excessive production of NO, $PGE_2$, TNF-${\alpha}$, and IL-1${\beta}$ in LPS-stimulated BV2 cells. In addition, GHE attenuated the mRNA expressions and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines. Conclusion: The anti-inflammatory properties of GHE may make it useful as a therapeutic candidate for the treatment of human neurodegenerative diseases.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.288-298
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• 2011

Background: Salvia miltiorrhiza (SM) has been used to treat inflammatory diseases including edema and arthritis; however, the anti-inflammatory mechanism of SM action remains unresolved. Methods: The effects of an ethanol extract of SM (ESM) on pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and NO, and on anti-inflammatory cytokines including IL-4, IL-10, TGF-${\beta}$, and IL-1Ra have been studied in an attempt to elucidate the anti-inflammatory mechanism in murine macrophages. Results: ESM inhibited the production of pro-inflammatory cytokines via down-regulation of gene and protein expression whereas it increased the anti-inflammatory cytokines. Furthermore, ESM inhibited the expression of the chemokines, RANTES and CX3CL1, as well as of inflammatory mediators such as TLR-4 and $11{\beta}$-HSD1. Conclusion: These results indicated that the regulatory effects of ESM may be mediated though the suppression of pro-inflammatory cytokines as well as the induction of anti-inflammatory cytokines. Consequently, we speculate that ESM has therapeutic potential for inflammation-associated disorders.

• Korean Journal of Plant Resources
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• v.30 no.3
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• pp.280-286
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• 2017

Barbaloin is a major component of Aloe vera, which has been used for a laxative. Also, barbaloin is C-glucoside of aloe emodin anthrone which is founded in Aloe vera. Barbaloin has varieties of pharmacological activity such as inhibitory effects on inflammation, histamine release, cancer and microbial infection. But the effect of barbaloin on lipopolysaccharide (LPS)-stimulated macrophages has not been understood. In this study, we evaluated the effects of barbaloin against LPS-stimulated production of nitric oxide (NO), inflammatory cytokines and MAPKs activation in macrophage. We treated barbaloin (0.1, 1, 10, $100{\mu}M$) in LPS-stimulated mice peritoneal macrophage. Our results showed that barbaloin significantly inhibited production of NO and cytokines of tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, interleukin $(IL)-1{\beta}$ in LPS-stimulated peritoneal macrophage. Moreover, barbaloin inhibited the phosphorylation of ERK and JNK in a dose dependent manner. These results indicated that barbaloin could be useful for inflammatory diseases.

• The Korea Journal of Herbology
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• v.22 no.1
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• pp.111-117
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• 2007

Objectives : The purpose of this study was to investigate the anti-inflammatory effects of extract from Pulsatilla koreana $N_{AKAI}$ (PK) on the peritoneal macrophage. Methods : To evaluate of anti-inflammatory of PK, we examined cytokines and NO production in lipopolysacchride (LPS)-induced macrophages. Furthermore, we examined molecular mechanism using western blot. Results : 1.Extract from PK reduced LPS-induced NO, tumor necrosis factor-a ($TNF-{\alpha}$), interleukin (IL)-6 and IL-12 production in peritoneal macrophages. 2.Extract from PK itself does not have any cytotoxic effect. PK inhibited the activation of extracelluar signal-regulated kinase(ERK 1/2) but not another mitogen-activated protein kinases (MAPKs) such as p38, c-Jun NH2-terminal kinase (JNK) and the degradation of inhibitory kappa B a ($I_{k}B_{a}$) does not any effect in the LPS-stimulated peritoneal macrophages. Conclusion : PK down-regulated LPS-induced NO and cytokines production, which may be provide a clinical basis for anti-inflammatory properties of PK.

• Journal of Ginseng Research
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• v.30 no.4
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• pp.181-187
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• 2006

Protopanaxadiol (PPD) is a mixture of protopanaxadiol type saponins with a dammarane skeleton, from Korean red ginseng (Panax ginseng C.A. Meyer; Araliaceae). Korean ginseng is well-known herb to treat almost all kinds of diseases in Oriental medicine. This herb was particularly prescribed for treatment various inflammatory diseases, including rheumatoid arthritis, atherosclerosis, and diabetes mellitus, for centuries. To understand the efficacy of ginseng against inflammatory diseases, we aimed to show anti-inflammatory activities of the PPD in murine macrophage cell line, RAW264.7 cells using nitric oxide (NO) production assay and the expressions of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and IL-6, and monocyte chemotactic protein-1 (MCP-1). We found that PPD saponin significantly blocked LPS ($1{\mu}g/ml$)-induced NO production in a dose-dependent manner. In addition, PPD abrogated the expressions of LPS-induced pro-inflammatory cytokines, such as IL-$1{\beta}$ and MCP-1. Moreover, cyclooxygenase (COX)-2, a critical enzyme to produce prostaglandin E2 (PGE2), was significantly inhibited by PPD in LPS-activated RAW264.7 cells. Taken together, these results suggested that anti-inflammatory efficacy of Korean red ginseng on inflammatory diseases is, at least, due to the NO inhibitory activity and the inhibition of the expressional level of inflammatory cytokines and/or mediators.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.333-338
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• 2015

Our previous report showed that the extract from cuttlebone (CB) had wound healing effect in burned lesion of rat and the extract was identified as chitin by HPLS analysis. We herein investigated the morphology in CB extract using scanning electron microscope (SEM). Chitin was used as a control. There is no difference in morphology between CB extract and chitin. We also assessed the role of CB extract on the production of inflammatory mediators using murine macrophages and the migration of inflammatory cells. The extract induced the production of nitric oxide (NO) in macrophages. While the extract of CB itself stimulated macrophages to increase the expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6, CB extract suppressed the production of those cytokines by LPS. CB extract also induced the production of mouse IL-8 which is related to the cell migration, and treatment with CB enhanced fibroblast migration and invasion. Therefore, our results suggest that CB activates inflammatory cells to enhance the cell migration.

• The Korea Journal of Herbology
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• v.25 no.3
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• pp.19-25
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• 2010

Objective : The aim of this study was to investigate anti-inflammatory activity of SD-01 methanol extract in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods : Cytotoxic activity of SD-01 methanol extract on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. The nitric oxide (NO) production was measured by Griess reagent system. And proinflammatory cytokines and $PGE_2$ were measured by ELISA method. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), $I{\kappa}$-B-alpha and nuclear NF-${\kappa}$ B p65 expression were detected by western blot. Results : Our results indicated that methanol extract of SD-01 significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-$\alpha$, IL-$1\beta$, IL-6 and MCP-1 production in RAW 264.7 cells. Moreover, methanol extract of SD-01 treatment also blocked LPS-induced NF-kB activation. Conclusion : These findings indicate that methanol extract of SD-01 inhibits the production of pro-inflammatory mediators and cytokines via suppression of NF-${\kappa}$ B activation. Take together, these results indicate that methanol extract of SD-01 has the potential for use as an agent of anti-chronic inflammatory diseases.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.2
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• pp.1-11
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• 2014

Objectives: The purpose of this study was to investigate the effects of Longanae Arillus water extract (LA) on the production of inflammatory mediators in RAW 264.7 cell. LA is used for forgetfulness, insomnia, palpitation symptoms in korean medicine. Methods: In order to evaluate cytotoxicity of LA, cell viability was measured. To investigate anti-inflammatory effects of LA in the lipopolysacharide (LPS)-induced RAW 264.7 cell, the concentration of nitric oxide (NO) and cytokines were measured. And when p-value is below 0.05, it is judged to have the significant difference statistically. Results: 1. LA showed no cytotoxicity. 2. LA inhibited significantly the production on NO at the concentration of 50 and $200{\mu}g/ml$. 3. LA inhibited significantly the production on interleukin (IL)-$1{\beta}$ at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 4. LA inhibited significantly the production on tumor necrosis factor (TNF)-${\alpha}$ at the concentration of 50, 100 and $200{\mu}g/ml$. 5. LA inhibited significantly the production on lipopolysaccharide-induced chemokine (LIX) at the concentration of 25, 100 and $200{\mu}g/ml$. 6. LA inhibited significantly the production on regulated on activation normal T cell expressed and secreted (RANTES) at the concentration of $200{\mu}g/ml$. Conclusions: These results suggest that LA has anti-inflammatory effect.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.83-90
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• 2014

Objectives : This research has been done to investigate the anti-inflammatory effect of Coptidis Rhizoma extracts. Method : Coptidis Rhizoma was extracted by $100^{\circ}C$ water. The extract (CC : Extract of Coptis chinensis rhizome) was used to examine its effects on the cell viability of mouse macrophage Raw 264.7 cell line. Also the production of nitric oxide (NO), the c-jun N-terminalkinase (JNK) activation and the production of cytokines such as (IL)-5 were evaluated in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. After the CC and LPS were applied to Raw 264.7 cells which were cultured for 24 hours, the MTT assay was performed. Result : The CC extracts didn't affect the viability of macrophage cells. However, the extracts inhibited the NO production and the JNK activation significantly in LPS-stimulated macrophage cells treated with 100 and $200{\mu}g/mL$ concentrations. The CC extract, also, impeded the production of inflammation-related factors and cytokines such as KC, VEGF, MCP-1, GM-CSF, IL-$1{\alpha}$, IL-5, IL-6, and IL-12p40 in LPS-stimulated macrophage cells at the concentration higher than $25{\mu}g/mL$. The production of basic-FGF concentration of 50 and $100{\mu}g/mL$, the production of IP-10 at $100{\mu}g/mL$, and the production of IFN-${\gamma}$ at $25{\mu}g/mL$, respectively. Conclusion : The CC prepared using $100^{\circ}C$ water showed the significant anti-inflammatory effect such as the inhibition not only on the production of NO, KC, VEGF, MCP-1, GM-CSF, IL-$1{\alpha}$, IL-5, IL-6, and IL-12p40 in LPS-stimulated macrophage cells at or higher than the concentration of $25{\mu}g/mL$, but also on the JNK activation at 100 and $200{\mu}g/mL$.