• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.353-358
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• 2010

This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-${\kappa}B$/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and Western blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-${\kappa}B$/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-${\kappa}B$/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-${\kappa}B$/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-${\kappa}B$/Rel and p38 kinase signaling.

• YAKHAK HOEJI
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• v.55 no.2
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• pp.154-159
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• 2011

During the search for a novel compound that can inhibit NF-${\kappa}B$ activation, 6-hydroxy-7-methoxychroman-2-carboxylic acid phenyl amide (KL-1156) was identified as a good inhibitor of NF-${\kappa}B$ activation. In the present study, we describe the synthesis of methylchroman-2-carboxylic acid N-(disubstituted)phenylamide derivatives (1 and 2 serieses). In addition, their inhibitory effects of NF-${\kappa}B$ are compared with activity of KL-1156 and SAR (structure activity relationship) are explored.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.59-70
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• 2004

Objectives : Previous studies showed that treatment with Chungganhaeju-tang prevents hepatic inflammation and apoptosis in alcoholic liver disease. The purpose of our study is to determine if any relations exsists between the transcription factor $NF{\kappa}B$, an orchestrating expression of a large number of genes and inhibitory effects of Chungganhaeju-tang on ethanol induced apoptosis. Materials and Methods : To assess the role of $NF{\kappa}B$, we blocked NFkB activation by delivering to the kupffer cells $I{\kappa}B{\Delta}N$, a dominant negative $NF{\kappa}B$ inhibitor, and investigated if Chungganhaeju-tang still prevented apoptosis. Results : When $NF{\kappa}B$ activation was blocked, there was no inhibitory effect of Chungganhaeju-tang on ethanol induced apoptosis of kupffer cells. Conclusion : This result suggests that Chungganhaeju-tang protects the liver from ethanol induced apoptosis by activating the $NF{\kappa}B$ that plays a key role in porotecting mechanism and reducing inflammatory cytokine gene expression.

• BMB Reports
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• v.42 no.3
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• pp.148-153
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• 2009

Pyrrolidine dithiocarbamate (PDTC) is a stable anti-oxidant or pro-oxidant, depending on the situation, and it is widely used to inhibit the activation of NF-${\kappa}B$. We recently reported that PDTC activates the MIP-2 gene in a NF-${\kappa}B$-independent and c-Jun-dependent manner in macrophage cells. In this work, we found that PDTC activates signal transduction pathways in mouse ES cells. Among the three different mitogen-activated protein kinase (MAPK) pathways, including the extracellular-signal-regulated kinase (ERK), p38 MAP kinase, and stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathways, only the ERK pathway was significantly activated in mouse ES cells after stimulation with PDTC. Additionally, we observed a synergistic activation of ERK and induction of c-Fos after stimulation with PDTC in the presence of mouse embryonic fibroblast (MEF) conditioned medium. In contrast, another NF-${\kappa}B$ inhibitor, BMS-345541, did not activate the MAP kinase pathways or induce expression of c-Fos. These results suggest that changes in the presence of the NF-${\kappa}B$ inhibitor PDTC should be carefully considered when it used with mouse ES cells.

• Journal of Chest Surgery
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• v.50 no.3
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• pp.144-152
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• 2017

Background: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of $NF-{\kappa}B$ and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. Methods: We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and $NF-{\kappa}B$ was measured in the left ventricle. Results: Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not $NF-{\kappa}B$, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). Conclusion: MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, $NF-{\kappa}B$ expression levels were not related to UPS function.

• Journal of Nutrition and Health
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• v.51 no.4
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• pp.323-329
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• 2018

Purpose: The dried body of Scolopendra subspinipes mutilans has long been used as a traditional Korean medicinal food, but little is known about its mechanisms of action. In this study, we investigated the anti-inflammatory activities of Scolopendra subspinipes mutilans and possible mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methods: Cytotoxicity of Scolopendra subspinipes mutilans extract (SSME) was measured by MTT assay, anti-inflammatory activities were analyzed by nitric oxide (NO) production, the expression of inducible NO synthase (iNOS) and the mRNA level of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$) and interleukin-6 (IL-6). Nuclear translocation of nuclear factor-kappa B ($NF-{\kappa}B$) p65 subunit and degradation of inhibitory kappa B ($I{\kappa}B$) were examined by western blot. Results: SSME inhibited LPS-induced NO production and iNOS expression without cytotoxicity. Up-regulation of LPS-induced pro-inflammatory cytokines, $IL-1{\beta}$ and IL-6 was dose dependently attenuated by SSME. Exposure of pyrrolidine dithiocarbamate, an $NF-{\kappa}B$ specific inhibitor, accelerated the inhibitory effects of SSME on NO production and iNOS expression in LPS-stimulated cells. Moreover, translocation of $NF-{\kappa}B$ from the cytosol to the nucleus and degradation of $I{\kappa}B$ were decreased by treatment with SSME in LPS-induced cells. Conclusion: These results suggest that the SSME might have the inhibitory effects on inflammation, partly through inhibition of the $NF-{\kappa}B$ signaling pathway.

• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.393-397
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• 2019

Proteasome inhibitors can promote apoptosis and cell cycle arrest in cancer cells by inhibition of nuclear factorkappaB ($NF-{\kappa}B$) activation. The purpose of this study was to investigate the effects of persimmon leaf extract (PSE) on proteasome activity in HepG2 human liver cancer cells. PSE treatment inhibited the proteasome activity and $NF-{\kappa}B$ activation in a dose-dependent manner in HepG2 human liver cancer cells (p<0.05). PSE treatment increased the population of cells in G2/M and sub-G1 phases. The results suggested that PSE is one of the candidate substances that may be developed into a proteasome inhibitor.

• Fisheries and Aquatic Sciences
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• v.19 no.9
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• pp.35.1-35.6
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• 2016

Gliotoxin has been recognized as an immunosuppressive agent for a long time. Recently, it was reported to have antitumor properties. However, the mechanisms by which it inhibits tumors remain unclear. Here, we showed that gliotoxin isolated from the marine fungus Aspergillus fumigatus inhibited proliferation and induced apoptosis in HT1080 human fibrosarcoma cells. Gliotoxin repressed phosphorylation-dependent degradation of $I{\kappa}B-{\alpha}$, an antagonist of nuclear factor kappa B ($NF-{\kappa}B$), which is a known tumor-promoting factor. This coincided with a decrease in nuclear import of $NF-{\kappa}B$, suggesting its signaling activity was impaired. Moreover, gliotoxin increased intracellular reactive oxygen species (ROS). Since ROS have been known to inhibit $NF-{\kappa}B$, this may also contribute to gliotoxin's antitumorigenic effects. These results suggest that gliotoxin suppressed the activation of $NF-{\kappa}B$ by inhibiting phosphorylation and degradation of $I{\kappa}B-{\alpha}$ and by increasing ROS, which resulted in apoptosis of HT1080 cells. Cumulatively, gliotoxin is a promising candidate antagonist of $NF-{\kappa}B$, and it should be investigated for its possible use as a selective inhibitor of human fibrosarcoma cells.

• Korean Journal of Oriental Medicine
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• v.16 no.3
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• pp.155-166
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• 2010

Objetives : The purpose of this study was to examine the pathway of anti-allergic effects of Aconiti Ciliare Tuber (ACT). Methods : We examined cell viability, ${\beta}$-hexosaminidase release, pro-inflammatory cytokines secretion and mRNA expressions, nuclear factor-kappa B (NF-${\kappa}B$) (p65) activation, inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) degradation, and MAPKs activation from RBL-2H3 cells pre-treatment by ACT of 1.0 mg/ml, 2.0 mg/ml separately. Results : We observed that ACT reduced the secretion of ${\beta}$-hexosaminidase, TNF-${\alpha}$, IL-4 and the expression of COX-2 mRNA in RBL-2H3 cells. Futhermore, ACT inhibited the levels of activation of NF-${\kappa}B$ (p65) protein, ERK MAPK, and degradation of $I{\kappa}B-{\alpha}$ in RBL-2H3 cells. Conclusions : These results show that ACT has an anti-histamine effect and inhibitory effect of NF-${\kappa}B$ (p65) through regulation of $I{\kappa}B-{\alpha}$ degradation. This improves that ACT could be used as an anti-allergic medicine.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.442-452
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• 2007

Objectives : The purpose of this study was to investigate the toll-like receptor (TLR)-4 mediated anti-inflammatory effects of extract from Shigyungbanha-tang (SBT) on the peritoneal macrophage. Methods : To evaluate of TLR-4 mediated inflammatory of SBT. we examined NO and cytokine production in TRL-4 ligand (LPS : lipopolysaccharide) induced macrophages. Furthermore, we examined its molecular mechanism using western blot. Results : Extract from SBT itself does not have any cytotoxic effect in the peritoneal macrophages. Extract from SBT reduced LPS-induced nitric oxide (NO). tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin (IL)-6 and IL-12 production in peritoneal macrophages. SBT inhibited degradation of inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) in the TLR-4 mediated peritoneal macrophages. Conclusions : These results suggest that SBT inhibits NO and cytokines production through inhibiting nuclear factor-kappaB (NF-${\kappa}$B) activation in peritoneal macrophage and that SBT may be beneficial oriental medicine for inflammation.