• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.110-118
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• 2015

According to the expansion of lifespan, neuronal disorder based on inflammation has been social problem. Therefore, we isolated shikonin from Lithospermum erythrorhizon and evaluated anti-inflammatory effects of shikonin in lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose-dependently inhibits the expression of the proinflammatory mediators, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-${\kappa}B$ (TNF-${\alpha}$) as well as their main regulatory genes and products such as inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-${\alpha}$ in LPS-stimulated BV2 microglial cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) to regulate the key regulatory genes of the proinflammatory mediators, such as iNOS, COX-2, and TNF-${\alpha}$, accompanied with downregulation of reactive oxygen species (ROS) generation. The results indicate that shikonin may downregulate the expression of proinflammatory genes involved in the synthesis of NO, $PGE_2$, and TNF-${\alpha}$ in LPS-treated BV2 microglial cells by suppressing ROS and NF-${\kappa}B$. Taken together, our results revealed that shikonin exerts downregulation of proinflammatory mediators by interference the ROS and NF-${\kappa}B$ signaling pathway.

• Journal of Periodontal and Implant Science
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• v.34 no.2
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• pp.461-474
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• 2004

The purpose of this study was to assess some biological activities of lipopolysaccharides (LPSs) from P. intermedia and P. nigrescens. LPS was prepared by the standard hot phenol-water method. NO production was assayed by measuring the accumulation of nitrite in culture supernatants. $TNF-{\alpha}$ production was determined by enzyme-linked immunosorbent assay. Western blot analysis of iNOS and analysis of reverse transcription (RT)-PCR products were carried out. LPS from P. intermedia demonstrated higher KDO content than those from two stains of P. nigrescens. LPSs from P. intermedia and P. nigrescens were mitogenic for spleen cells of BALB/C mouse. The present study clearly shows that LPSs from P. intermedia and P. nigrescens fully induced iNOS expression and NO production in RAW264.7 cells in the absence of other stimuli. Moreover, LPSs from P. intermedia and P. nigrescens clearly induced $TNF-{\alpha}$ production in RAW264.7 cells. The biological activities of LPS from P. intermedia was found to be comparable to those of P. nigrescens LPS. The ability of LPSs from P. intermedia and P. nigrescens to promote the production of NO and $TNF-{\alpha}$ may be important in the pathogenesis of inflammatory periodontal disease.

• Journal of Applied Biological Chemistry
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• v.60 no.3
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• pp.199-205
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• 2017

To investigate the anti-inflammatory activity of natural products, we determined the anti-inflammatory activity of purified epigallocatechin (EGC) from Camellia sinensis leaves. In the present study, we found that EGC inhibited the production of proinflammatory mediators (IL-6, TNF-${\alpha}$, NO, and $PGE_2$) in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. Suppression of IL-6 seems to be at least partly attributable to the inhibitory effect of EGC. TNF-${\alpha}$ is a major cytokine produced by LPS-induced macrophages, and they have a wide variety of biological functions including regulation of inflammation. The inhibition of IL-6 and TNF-${\alpha}$ production by EGC may downregulate the acute-phase response to LPS, thereby reducing LPS-induced inflammation. In addition to IL-6 and TNF-${\alpha}$, EGC effectively reduced the production of other key inflammatory mediators, including NO and $PGE_2$. The inhibitory effect of EGC on NO and $PGE_2$ production was supported by the suppression of inducible nitric oxide synthase and COX-2 at protein levels. These results support the traditional use of EGC in the alleviation of various inflammation-associated diseases and suggest that EGC might be useful in the development of new functional foods for inflammatory diseases.

• YAKHAK HOEJI
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• v.46 no.5
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• pp.343-347
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• 2002

In the present study, effects of essential oils isolated from various plants have been evaluated on lipopolysaccharide (LPS)-induced release of nitric oxide (NO), prostaglandin E$_2$(PGE$_2$) and tumor necrosis factor-a (TNF-$\alpha$) by the macrophage RAW 264.7 cells. Among the tested essential oils, essential oil of Ligularia fischeri var. spiciformis (LF-oil) significantly inhibited the LPS-induced generation of NO, PGE$_2$ and TNF-$\alpha$ in Raw 264.7 cells. Consistent with these observations, the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzyme was inhibited by LF-oil in a concentration-dependent manner. Thus, this study suggests that inhibition of release of iNOS, COX-2 expression, and TNF-$\alpha$ by the essential oil of Ligularia fischer may be one of the mechanisms responsible for the anti-inflammatory effects of this medicinal plant.

• Journal of Oriental Neuropsychiatry
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• v.11 no.2
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• pp.11-21
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• 2000

Substance P(SP) can stimulate production of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) from astrocytes stimulated with lipopolysaccharide(LPS). The objective of the current study was to determine the effect of Taraxacum officinale(TO) on the production of TNF-${\alpha}$ from primary cultures of rat astrocytes. TO(100& 1000$\mu\textrm{g}$/ml) significantly inhibited the TNF-${\alpha}$ production by astrocytes stimulated with LPS and SP. Interleukin-1(IL-1) has been shown to elevate TNF-${\alpha}$ production from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-${\alpha}$ production from primary astrocytes by TO. Treatment of TO(100 and 1000$\mu\textrm{g}$/ml) to astrocytes stimulated with both LPS and substance P decreased IL-1 production significantly. Moreover, the production of TNF-${\alpha}$ by LPS and substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. These results suggest that TO may inhibit TNF-${\alpha}$ production by inhibiting IL-1 production and that TO has an antiinflammatory activity in the central nervous system.

• Journal of the East Asian Society of Dietary Life
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• v.24 no.6
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• pp.776-784
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• 2014

Korean dishes, Hansik are characterized by healthful vegetable intake. The purpose of this study was to evaluate the inhibitory effect of commonly consumed vegetables by Koreans on obesity/metabolic disease-related inflammation. Through statistical analysis of the KNHANES database ($1^{st}$ 1998, $5^{th}$ 2010, 2011) and a literature review, we selected vegetables for study. Among the vegetables, main or sub ingredients of Kimchi were excluded. Samples were prepared using only edible portions and freeze-dried. After grinding, samples were extracted with ethanol, evaporated and finally lyophilized. The cytotoxicity of samples was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, at various concentrations that do not affect cell viability. Raw 264.7 macrophages were treated with lipopolysaccharide (LPS) and 11 kinds of samples or positive control (troglitazone) dissolved in dimethyl sulfoxide (DMSO). After 24 hours, nitric oxide (NO), tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and monocyte chemoattractant protein-1 (MCP-1) production were determined. Excepts for young pumpkin and bracken, nine samples effectively reduced NO production compared with control treated with LPS and DMSO. NO levels of five samples (bean sprouts, leeks, eggplant, mugwort, and pumpkin) were similar to that of the positive control. These five samples showed significantly decreased TNF-${\alpha}$ or MCP-1 compared to the control group. Our results suggest that consumption of commonly consumed vegetables contributes to partial prevention of obesity and related metabolic syndrome through reduction of NO, TNF-${\alpha}$, and MCP-1 production.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.2
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• pp.152-165
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• 2008

Purpose: It is the purpose of this study to investigate the anti-inflammatory effects and mechanism of cheukbaekjurpihwan(CBJPH) extract on LPS (lipopolysaccharide)-induced inflammatory mediators in murine peritoneal macrophages. Methods: To evaluate anti-inflammatory effects of CBJPH extract, the production of cytokines(TNF-${\alpha}$(tumor necrosis factor-alpha), IL(interleukin)-6, IL-12) and NO(nitric oxide) was measured in vitro and in vivo. And western blot analysis has been done to look into the mechanism. Results: CBJPH extract reduced LPS-induced NO, TNF-${\alpha}$ and IL-6, IL-12 productions in peritoneal macrophages. CBJPH extract inhibited the activation of JNK(c-Jun N-terminal kinase), but didn't inhibit the activation of MAPKs (mitogen-activated protein kinases) such as p38, ERK1/2(extracelluar signal-regulated kinase1/2) and the degradation of $I_{\kappa}B-{\alpha}$(inhibitory kappa B-alpha) in the LPS-stimulated peritoneal macrophages. CBJPH extract suppressed LPS-induced endotoxin shock and the productions of TNF-${\alpha}$, but not of IL-6, after an oral administration of CBJPH extract Conclusion: CBJPH extract suppressed the productions of LPS-induced NO and cytokines by preventing JNK from phosphorylation, which may provide a clinical basis for anti-inflammatory properties of CBJPH.

• YAKHAK HOEJI
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• v.59 no.5
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• pp.215-221
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• 2015

Glucocorticoids are known to have anti-inflammatory effect. To investigate whether corticosterone pretreatment enhances or not lipopolysaccharide (LPS)-induced production of inflammatory mediators, RAW 264.7 cells were pretreated with various concentrations of corticosterone for 24 h and then cultured without corticosterone in the presence or absence of LPS. Our results demonstrated that LPS remarkably increased production of TNF-${\alpha}$, IL-6, IL-$1{\beta}$, vascular endothelial growth factor (VEGF), and NO (nitric oxide). Corticosterone pretreatment significantly attenuated LPS-induced production of TNF-${\alpha}$, IL-$1{\beta}$, and VEGF, while significantly enhanced IL-6 and NO. These findings suggest that corticosterone pretreatment may contribute to LPS-induced inflammatory responses in macrophages via pro- and anti-inflammatory imbalance of inflammatory mediators.

• Journal of Korean Neurosurgical Society
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• v.29 no.4
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• pp.477-484
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• 2000

Objective : Despite advances in the understanding of tumor biology and the tumor immunology, there has been no effective treatment. The Intercellular adhesion molecule-1(ICAM-1) has been shown to be important in interaction involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon($IFN-{\gamma}$) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$). ICAM-1 has been identified as one of the ligands for lymphocyte function-associated antigen-1(LFA-1). The effectiveness of various cytokines to ICAM-1 induction on cultured human glioblastoma cell lines and potential efficacy of immunotherapy were studied. Method : Human glioblastoma cell lines, U-251 MG, U-373 MG were trypsinized and suspended at $1{\times}10^5cells/ml$ and grown on 8 well chamber slide, the cells were incubated in 0.3ml medium alone or medium containing $IFN-{\gamma}$(1000U/ml) or $TNF-{\alpha}$(250U/ml) or $IFN-{\gamma}$ plus $TNF-{\alpha}$ for 6, 12, 24, 48 and 72 hours. The coverslip were then removed and stained with a 1/30 dilution of anti-ICAM-1 antibody. Result : Surface antigen expression of ICAM-1 was increased by incubating glioblastoma cell lines with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\gamma}$ and $TNF-{\alpha}$ has induced more ICAM-1 expression on glioblastoma cell lines. Upregulation of ICAM-1 expression in an established glioblastoma cell line was of greater magnitude and more rapid following incubation with $IFN-{\gamma}$ plus $TNF-{\alpha}$. Surface antigen expression of ICAM-1 was increased for up to 48 hours after cytokine treatment on both cell lines(p<0.05). There was no difference on both cell lines(p>0.05). Conclusion : The results of the present study indicate that ICAM-1 expression in glioblastoma cell lines, U-251 MG and U-373 MG, are induced and enhanced after treatment with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\alpha}$ and $TNF-{\gamma}$ is stronger and more rapid than $IFN-{\gamma}$ or $TNF-{\alpha}$ alone.

• Korean Journal of Plant Resources
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• v.23 no.5
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• pp.399-405
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• 2010

Rosa rugosa has been used as a folk medicine with various pharmacological properties for a long time in Asia. Recently, it has been reported that the extract of fractions from different parts of Rosa rugosa have various pharmacological effects on diverse diseases including diabetes, inflammatory diseases and tumor. We investigated effects of fructus extracts of Rosa rugosa(RRF) and semen extracts of this herb(RRS) on macrophage to evaluate the possibilities as a biological response modifier. We showed increased effects on tumoricidal activity, phagocytic activity, TNF-$\alpha$ and NO production in RRF-treated groups without direct tumor cell cytotoxicity. RRS-treated groups increased direct tumor cell cytotoxicity at high dose without tumoricial activity except increasing of TNF-$\alpha$ release. These results provide further possibilities for the beneficial immunomodulating effects of RRF on immune system with relatively larger safety margin rather than RRS.