• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.90-97
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• 2015

Water chestnut (Trapa japonica Flerov.) is an annual aquatic plant. In the present study, we showed that the treatment of water chestnut extracted with boiling water resulted in a significant increase 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and decrease the intracellular $H_2O_2$-induced accumulation of reactive oxygen species. In addition, water chestnut extract (WCE) inhibited lipopolysaccharide (LPS)-induced nitric oxide production and suppressed mRNA and protein expression of the inducible nitric oxide synthase gene. The cytokine array results showed that WCE inhibited inflammatory cytokine secretion. Also, WCE reduced tumor necrosis factor-${\alpha}$- and interleukin-6-induced nuclear factor-${\kappa}B$ activity. Furthermore, during sodium lauryl sulfate (SLS)-induced irritation of human skin, WCE reduced SLS-induced skin erythema and improved barrier regeneration. These results indicate that WCE may be a promising topical anti-inflammatory agent.

• BMB Reports
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• v.48 no.3
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.435-441
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• 2013

Emodin, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, has several beneficial pharmacologic effects, which include anti-cancer, anti-diabetic, and anti-inflammatory activities. In this study, the authors examined the effect of emodin on the production of proinflammatory cytokines, such as, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the mechanism responsible for the regulation of pro-inflammatory cytokine production by emodin, the authors assessed its effects on the activations of transcriptional factor nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and mitogen-activated protein kinases (MAPKs). Emodin attenuated the nuclear translocation of (NF)-${\kappa}B$ p65 and its DNA-binding activity by reducing the phosphorylation and degradation of $I{\kappa}B{\alpha}$ and the phosphorylation of $I{\kappa}B$ kinase B (IKK). Furthermore, emodin dose-dependently attenuated the phosphorylations of MAPKs, such as, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase, and the stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK). Taken together, the findings of this study suggest that the anti-inflammatory effects of emodin on PMA plus A23187-stimulated BMMCs are mediated via the inhibition of NF-${\kappa}B$ activation and of the MAPK pathway.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.3
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• pp.82-93
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• 2008

Objective: Previously, the methanol extracts of the semen of Xanthium strumsrium could involved anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated Raw 264,7 cells, We evaluated the anti-allergic effects of X. strumarium on rat basophilic leukemia (RBL-2H3) cells, Methodes : To investigate the effect of X. strumarium on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced RBL-2H3 cells. The effects of X. strumarium on the degranulation and the pro-inflammatory cytokines secretion and expression from RBL-2H3 cells were evaluated with $\beta$-hexosaminidase assay, ELISA, and RT-PCR analysis, In addition, we examined the effects of X. strumarium on nuclear factor (NF)-${\kappa}B$ activation and $I{\kappa}B-\alpha$ degradation using Western blot analysis. Results : X. strumarium inhibited degranulation and secretions and expressions of pro-inflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-\alpha$), interleukin (IL)-4 and cyclooxygenase (COX)-2, on stimulated RBL-2H3 cells, however, X. strumarium not affect cell viability. In stimulated RBL-2H3 cells, the protein expression level of nuclear factor-kappa B (NF-${\kappa}B$) was decreased in the nucleus by X. strumarium. In addition, X. strumarium suppressed the degradation of inhibitory protein $I{\kappa}B-{\alpha}$ protein in RBL-2H3 cells. Conclusion : These results suggest that X. strumarium inhibits the degranulation and secretion of pro-inflammatory cytokines through blockade of NF-${\kappa}B$ activation and I $I{\kappa}B-{\alpha}$ degradation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.1017-1024
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• 2007

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via $CCR4^+$ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and $I{\kappa}B{\alpha}$ phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-${\alpha}$ and IFN-${\gamma}$. Wogonin inhibited NF-${\kappa}B$-DNA complex, NF-${\kappa}B$ binding activity, and the phosphorylation of $I{\kappa}B{\alpha}$ in a dose dependent manner. Wogonin also inhibited the translocation of NF-${\kappa}B$ from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-${\alpha}$ and IFN-${\gamma}$-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-${\kappa}B$ activation by $I{\kappa}B{\alpha}$ degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

• BMB Reports
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• v.35 no.1
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• pp.28-40
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• 2002

Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-${\kappa}B$ activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-${\kappa}B$ and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which mayor may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-${\kappa}B$ controls apoptosis.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.202-210
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• 2018

Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum flower (ADF) extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor NF-${\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADF significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-${\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the flower extract has potential therapeutic benefits against various inflammatory diseases.

• Journal of agriculture & life science
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• v.50 no.2
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• pp.151-160
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• 2016

Inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. Sulforaphane, isolated from the Broccoli(Brassica oleracea var. italia) florets, inhibits the production of inflamatory cytokine. In the present study, we determined inhibitory effect of sulforaphane on Receptor activator of nuclear factor κB ligand(RANKL)-induced osteoclast formation. Sulforaphane inhibited the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase(TRAP), cathepsin K, matrix metalloproteinase 9(MMP-9), and calcitonin receptor in RANKL-induced RAW 264.7 macrophage. Also, sluforaphane inhibited the expression of osteoclast protein, such as TRAP, MMP-9, tumor necrosis factor receptor-associated factor 6(TRAF6) and transcription factor nuclease factor of activated T cells(NFAT)c1. Sulforaphane inhibited RANKL-induced activiation of nuclear factor kappaB(NF-kappaB) by suppression RANKL-mediated NF-kappaB transcriptional acitivation. We are confirmed that sulforaphane inhibits not only transcriptional activity of NF-kappaB but also expressions of the osteoclastogenesis factors(TRAP, cathepsin K, MMP-9, calcitonin, TRAF6) and trranscription factor NFATc1.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.2
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• pp.1-15
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• 2017

Objectives: The object of this study was to identify the anti-inflammatory effects of Patrinia scabiosaefolia aqueous extract (PSE). Methods: RAW 264.7 cells were pre-treated with PSE and then incubated with or without lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), secretion of pro-inflammatory cytokine, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-${\kappa}B$) were measured. In addition, we observed mice survival rate after LPS and their cytokine levels of serum. We also observed inflammatory and hemorrhagic change on the histological sections of the liver. Results: PSE inhibited LPS-induced NO production, interleukin (IL)-6 secretion, c-Jun NH2-terminal kinase (JNK) and NF-${\kappa}B$ activation. In addition, PSE reduced the death rate of LPS-induced mice and IL-6 production on the serum of mice. PSE inhibited inflammation and hemorrhage on liver tissue as well. Conclusions: The results suggest that PSE have anti-inflammatory effects by inhibited NF-${\kappa}B$ and JNK activation, IL-6 secretion, and NO production. So PSE may be effective treatment for the inflammatory disease.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.15-22
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• 2014

Aggregatibacter actinomycetemcomitans is an important pathogen in the development of localized aggressive periodontitis. Lipopolysaccharide (LPS) is a virulent factor of periodontal pathogens that contributes to alveolar bone loss and connective tissue degradation in periodontal disease. Our present study was designed to investigate the cytokine expression and signaling pathways regulated by A. actinomycetemcomitans LPS (Aa LPS). Cytokine gene expression profiling in RAW 264.7 cells was performed by microarray analyses. The cytokine mRNA and protein levels and related signaling pathways induced by Aa LPS were measured by RT-PCR, ELISA and western blotting. Microarray results showed that Aa LPS strongly induced the expression of NF-${\kappa}B$, NF-${\kappa}B$-related genes, inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in RAW 264.7 cells. NF-${\kappa}B$ inhibitor pretreatment significantly reduced the levels of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA and protein. In addition, the Aa LPS-induced TNF-${\alpha}$ and IL-$1{\beta}$ expression was inhibited by p38/JNK MAP kinase inhibitor pretreatment. These results show that Aa LPS stimulates TNF-${\alpha}$ and IL-$1{\beta}$ expression through NF-${\kappa}B$ and p38/JNK activation in RAW 264.7 cells, suggesting the essential role of this pathway in the pathogenesis of localized aggressive periodontitis.