• Korean Journal of Food Science and Technology
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• v.40 no.3
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• pp.332-336
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• 2008

Ginger is widely used as a traditional herbal medicine. Both ginger and its extracts have been used to treat many chronic inflammatory conditions via the inhibition of nuclear factor-kappa B (NF-${\kappa}B$) activation, which results in the suppression of cyclooxygenase-2 (COX-2) expression. However, the mechanisms as to how ginger extracts mediate their health effects are largely unknown. Toll-like receptors (TLRs) trigger anti-microbial innate immune responses, recognizing conserved microbial structural molecules that are known as pathogen-associated molecular patterns. All TLR signaling pathways culminate in the activation of NF-${\kappa}B$. The activation of NF- ${\kappa}B$ leads to the induction of inflammatory gene products, including cytokines and COX-2. This study reports the biochemical evidence that 6-shogaol, an active compound in ginger, inhibits NF-${\kappa}B$ activation and COX-2 expression induced by TLR2, TLR3, and TLR4 agonists. Furthermore, 6-shogaol inhibited NF-${\kappa}B$ activation induced by the following downstream signaling components of the TLRs: MyD88, $IKK{\beta}$, and p65. These results imply that ginger can modulate immune responses that could potentially modify the risk of many chronic inflammatory diseases.

• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.820-826
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• 2019

This study evaluated the anti-inflammatory potential of a grasshopper ketone (GK) isolated from the brown alga Sargassum fulvellum on lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophage cell line. GK was isolated and purified from the n-hexane fraction and its structure was verified on the basis of NMR spectroscopic data. GK up to $100{\mu}g/ml$ is not cytotoxic to RAW 264.7, and is an effective inhibitor of LPS-induced NO production in RAW 264.7 cells. The production of pro-inflammatory cytokines, including IL-6, $IL-1{\beta}$, and $TNF-{\alpha}$ was found significantly reduced in $0.1-100{\mu}g/ml$ dose ranges of GK treatment (p < 0.05). We confirmed the dose-dependent and significant inhibition of iNOS and COX-2 proteins expression. In addition, it has been shown that GK induces anti-inflammatory effects by inhibiting MAPKs (ERK, JNK, and p38) and $NF-{\kappa}B$ p65 phosphorylation. Our results show that the anti-inflammatory properties of GK may be due to the inhibition of the $NF-{\kappa}B$ and MAPKs pathways, which are associated with the attenuation of cytokine secretion.

• Journal of Life Science
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• v.20 no.3
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• pp.388-395
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• 2010

Cyclooxygenase (COX)-2 is generally known as an inducible enzyme, and it produces arachidonic acid to prostaglandin $E_2$ ($PGE_2$), which has been demonstrated to play a critical role in inflammation. In the present study, we investigated the effects of the extracts of fermented beans including soybean (FS), black agabean (FBA) and yellow agabean (FYA), on the expression of COXs and production of $PGE_2$ in U937 human promonocytic cells. Treatment of phorbol 12-myristate 13-acetate (PMA) significantly induced pro-inflammatory mediators such as COX-2 expression and $PGE_2$ production, whereas the levels of COX-1 remained unchanged. However, pre-treatment with FS, FBA and FYA significantly decreased PMA-induced COX-2 protein as well as mRNA, which is associated with inhibition of $PGE_2$ production. Moreover, FS, FBA and FYA markedly prevented the increase of nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$) p65 by PMA. Our data indicate that the extracts of fermented beans exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the NF-${\kappa}B$ signaling pathway.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1180-1188
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• 2017

Neuronatin (NNAT) is known to regulate ion channels during brain development and plays a role in maintaining the structure of the nervous system. A previous in silico analysis showed that Nnat was overexpressed in the adipose tissue of an obese rodent model relative to the wild type. Therefore, the aim of the present study was to investigate the function of Nnat in the adipose tissue. Because obesity is known to systemically induce low-grade inflammation, the Nnat expression level was examined in the adipose tissue obtained from C57BL/6 mice administered lipopolysaccharide (LPS). Unexpectedly, the Nnat expression level decreased in the white adipose tissue after LPS administration. To determine the role of NNAT in inflammation, 3T3-L1 cells overexpressing Nnat were treated with LPS. The level of the p65 subunit of nuclear factor-kappa B ($NF-{\kappa}B$) and the activity of $NF-{\kappa}B$ luciferase decreased following LPS treatment. These results indicate that NNAT plays an anti-inflammatory role in the adipose tissue.

• The Journal of Korean Medicine
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• v.32 no.2
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• pp.1-13
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• 2011

Background and Objective: Coptidis Rhizoma is a medicinal herb known for its antioxidant and anti-inflammatory effect. The purpose of this study was to examine the effects of CR on the experimental burn elicitation in vitro and in vivo. Material and Methods: In order to know the antioxidant effect on skin cell of mice after burn elicitation, superoxide dismutase (SOD) activity was measured. In vitro, the RAW 264.7 macrophage cells were treated with lipopolysaccharides for experimental inflammation. iNOS mRNA expression was observed after CR-treatment. In order to know effects on the skin regeneration in the burned mice, we counted the nitric oxide (NO) in blood. We also observed the histological structure in the epidermal basal layer and the dermal section, and we studied changes of angiogenesis in the capillaries surrounding the basal layer and dermal papilla. The changes of transcription of iNOS mRNA (inducible nitric oxide synthase mRNA) and changes of NF-${\kappa}$B (nuclear factor ${\kappa}$B) p65 positive reaction were also observed to investigate the changes of the stress in the skin. Results: The results indicated that CR has significant effects on the antioxidant effect on skin cells of mice after burn elicitation by increasing SOD activity in the in vitro test. It seemed that CR decreased the amount of NF-${\kappa}$B which induced the iNOS mRNA dose-dependently and suppress activating NO and angiogenesis. Furthermore, CR facilitated the process of skin recovery after experimental burn. Conclusion: CR can be applied for burned skin via antioxidant effect and skin regeneration.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.107-121
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• 2010

Objective: This study aimed to ascertain the curative effects of Gamisipjeon-tang (GST) used for wound healing on the skin regeneration of deep second degree burns in mice. Material & Methods: In vitro, the $I{\kappa}B$ kinase (IKK) mRNA expression, inducible nitric oxide synthase (iNOS) mRNA expression, and cyclooxygenase-2 (COX-2) mRNA expression in the GST concentration from 1 mg/$m{\ell}$ to 10 mg/$m{\ell}$ were measured. In vivo, the mice were divided into four groups : the normal group, the BE group (burn-elicited group, control group), the DC group (Duoderm CGF-treated group after burn elicitation), and the GST group (Gamisipjeon-tang treated group after burn elicitation). To determine the anti-inflammatory effects, nuclear factor (NF)-${\kappa}B$ p65, iNOS, COX-2 positive reaction were measured by immunohistochemistry. To estimate the skin regenerative effects, change of burn area, 5-bromo-2'-deoxyuridine (BrdU), and fibroblast growth factor (FGF) positive reaction were analyzed. Results: In vitro, the iNOS, IKK, COX-2 mRNA expression decreased according to the increase of GST concentration. The significant decrease of COX-2, iNOS, NF-${\kappa}B$ positive reaction were the highest in the GST group, followed by the DC group and the BE group (p<0.05). The diameter of burn area was significantly decreased in the GST group as compared to that in the DC and BE group (p<0.05). The BrdU and FGF positive reaction increased more significantly in the GST group than in the DC group, and more significantly in the DC group than in the BE group on the 3rd and 7th day after burn (p<0.05). FGF positive reaction increased in the BE and DC group, whereas it decreased significantly in the GST group on the 14th day (p<0.05). The BrdU positive reaction increased in the BE group, whereas it decreased significantly in the DC and GST group on the 14th day (p<0.05). Conclusions: This study shows that GST could decrease the inflammatory response and accelerate the skin regeneration as compared to the duoderm CGF in mice with deep second degree burns.

• Natural Product Sciences
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• v.12 no.1
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• pp.38-43
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• 2006

Ilekudinol B is one of the flavonoids isolated from Weigela subsessilis (Caprifoliaceae). In the present study, the suppression effect of ilekudinol B on tumor necrosis factor $(TNF)-{\alpha}-induced$ cyclooxygenase-2 (COX-2) expression was investigated in human colon epithelial cell line HT-29. Interleukin-8 (IL-8) production and prostaglandin $E_2\;(PGE_2)$ secretion was measured by enzyme-linked immunosorbent assay (ELISA). COX-2 and nuclear factor $(NF)-{\kappa}B$ expression were determined by Western blot analysis. Ilekudinol B significantly inhibited $TNF-{\alpha}-induced$ secretion of IL-8 and prostaglandin $E_2\;(PGE_2)$ from the human colon epithelial cell line HT-29 in a concentration-dependent manner. In addition, ilekudinol B remarkably diminished $TNF-{\alpha}-induced$ COX-2 expression and $NF-{\kappa}B$ p65 subunit translocation to the nucleus. In conclusion, our results indicate that ilekudinol B may have anti-inflammatory activity on $TNF-{\alpha}-dependent$ colonic inflammation.

• Parasites, Hosts and Diseases
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• v.47 no.3
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• pp.205-212
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• 2009

Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis Iysates increased proinflammatory cytokines, such as TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by HMDM. The involvement of nuclear factor (NF)-${\kappa}B$ signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-${\kappa}B$. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-${\kappa}B$ activation and TNF-${\alpha}$ production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-${\kappa}B$ inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-${\alpha}$. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-${\alpha}$, and NO. In particular, we showed that T. vaginalis induced TNF-${\alpha}$ production in macrophages through NO-dependent activation of NF-${\kappa}B$, which might be closely involved in inflammation caused by T. vaginalis.

• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.227-234
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• 2014

The anti-inflammatory effect of Sargassum micracanthum water extract (SMWE) was investigated using lipopolysaccharide (LPS)-induced inflammatory response in this study. The murine macrophage cell line RAW 264.7 cells were used and MTT assay was performed to measure the cell proliferation ability. The secretion of nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and IL-$1{\beta}$ was measured in LPS-induced RAW 264.7 cells by ELISA. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear transcription factor-kappa B p65 protein was studied by immunoblotting. The Balb/c mice were used for an acute toxicity test, and imprinting control region mice were purchased to evaluate a croton oil-induced ear edema. As a result, there was no cytotoxicity in the macrophage proliferation treated with SMWE compared to the control. NO levels decreased with increasing concentration of SMWE and were inhibited over 50%. Moreover, the secretion of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed in a dose-dependent manner, especially, IL-$1{\beta}$ inhibition activity was over 50% at 50 ${mu}g$/mL. The formation of ear edema of mice was reduced at the highest dose tested compared to that in the control. Moreover, in acute toxicity test, no moralities occurred in mice administered 5,000 mg/kg body weight of SMWE over 2 weeks observation period. These results suggested that SMWE may have significant effects on inflammatory factors and be potential anti-inflammatory therapeutic materials.

• Journal of Microbiology and Biotechnology
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• v.23 no.12
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• pp.1691-1698
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• 2013

The anti-inflammatory effects of Sargassum micracanthum ethanol extract (SMEE) was investigated using LPS-induced inflammatory response in this study. As a result, there was no cytotoxicity in the macrophage proliferation treated with SMEE compared with the control. SMEE inhibited production of nitric oxide and cytokines (IL-6, TNF-${\alpha}$, and IL-$1{\beta}$) in a dose-dependent manner. In addition, the expression of inducible nitric oxide synthase and cyclooxygenase 2 were suppressed via inhibition of nuclear factor ${\kappa}B$ p65 expression by SMEE treatment. The formation of edema in the mouse ear was reduced at the highest dose tested compared with that in the control, and reduction of ear thickness was observed in histological analysis. Moreover, in an acute toxicity test, no mortalities occurred in mice administered 5,000 mg/kg body weight of SMEE over a 2-week observation period. These results suggest that SMEE may have significant effects on inflammatory mediators and be a potential anti-inflammatory therapeutic material.