• Journal of Nutrition and Health
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• 제51권4호
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• pp.323-329
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• 2018

만성 염증은 현대사회에서 다양한 질병을 유발하는 주요 원인으로 작용하기 때문에 항염증 활성을 가진 소재의 연구는 염증 관련 질병의 예방과 치료에 있어서 중요하다. 본 연구에서는 LPS에 의해 염증을 유도한 RAW 264.7 세포에서 제주왕지네 (Scolopendra subspinipes mutilans) 에탄올 추출물의 염증 조절 기전을 확인하여 항염증 소재로서의 가능성을 조사하였다. LPS에 의해 증가된 NO 생성과 iNOS 발현은 왕지네 추출물에 의해 감소되었고 pro-inflammatory cytokine으로 알려진 $IL-1{\beta}$, IL-6의 발현에서도 유사한 결과를 보였다. 왕지네 추출물은 LPS에 의해 유도된 $NF-{\kappa}B$의 핵으로의 전이와 $I{\kappa}B$의 분해를 동시에 억제하였고 $NF-{\kappa}B$ inhibitor의 처리는 NO 생성과 iNOS 발현을 더욱 억제하였다. 이상의 결과는 왕지네 추출물이 $NF-{\kappa}B$ 활성 조절을 통해 염증 반응의 지표로 사용되는 NO 생성 및 pro-inflammatory cytokine의 발현을 효과적으로 억제하여 항염 활성을 가진 소재로서의 가능성을 보여주는 것으로 염증에 의해 유발되는 다양한 질병을 효율적으로 제어하는 소재를 개발하는데 있어서 주요한 정보를 제공할 것으로 생각된다.

• BMB Reports
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• 제35권4호
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• pp.371-376
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• 2002

The receptor activator of nuclear factor kappa B (RANK) is a member of the tumor necrosis factor (TNF) receptor superfamily. It plays a critical role in osteoclast differentiaion, lymph node organogenesis, and mammary gland development. The stimulation of RANK causes the activation of transcription factors NF-${\kappa}B$ and activator protein 1 (AP1), and the mitogen activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). In the signal transduction of RANK, the recruitment of the adaptor molecules, TNF receptor-associated factors (TRAFs), is and initial cytoplasmic event. Recently, the association of the MAPK kinase kinase, transforming growth factor-$\beta$-activated kinase 1 (TAK1), with TRAF6 was shown to mediate the IL-1 signaling to NF-${\kappa}B$ and JNK. We investigated whether or not TAK1 plays a role in RANK signaling. A dominant-negative form of TAK1 was discovered to abolish the RANK-induced activation of AP1 and JNK. The AP1 activation by TRAF2, TRAF5, and TRAF6 was also greatly suppressed by the dominant-negative TAK1. the inhibitory effect of the TAK1 mutant on RANK-and TRAF-induced NF-${\kappa}B$ activation was also observed, but less efficiently. Our findings indicate that TAK1 is involved in the MAPK cascade and NF-${\kappa}B$ pathway that is activated by RANK.

• Journal of Acupuncture Research
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• 제21권6호
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• pp.19-36
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• 2004

Objective : The purpose of this study was to investigate the effect of Bee Venom and Melittin Solution on the lipopolysaccharide(LPS) and sodium nitroprusside(SNP)-induced expression of prostaglandin $E_2(PGE_2)$, cyclooxygenase-2(COX-2), nuclear factor kappa B($NF-{\kappa}B$) and nuclear factor kappa B($NF-{\kappa}B$) dependent luciferase activity in RAW 264.7 cells, a murine macrophage cell line. Methods : The expression of PGE2 was determined by determination of $PEG_2$, COX-2 was by western blotting with corresponding antibodies, $NF-{\kappa}B$ was by gel mobility shift assay method and $NF-{\kappa}B$ dependent luciferase activity was investigated by luciferase assay in RAW 264.7 cells. Results : 1. LPS and SNP-induced expression of $PEG_2$ was significant after 24hour. 2. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS-induced expression of $PEG_2$ and, the $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly SNP-induced expression of $PEG_2$ compared with control, respectively. The 0.5 and $1{\mu}g/mL$ of bee venom could not significantly inhibit SNP-induced expression of $PEG_2$ compared with control. 3. The $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5 and $1{\mu}g/mL$ of bee venom inclined to decrease LPS and SNP-induced expression of COX-2 compared with control. 4. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ compared with control, respectively. 5. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS-induced expression of $NF-{\kappa}B$ dependent luciferase activity and the 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control, respectively. The $NF-{\kappa}B$ inhibitor also inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control. 6. The 0.5, 1 and $5{\mu}g/mL$ of bee venom and the 5 and $10{\mu}g/mL$ of melittin solution inhibited significantly LPS + IFN-${\gamma}$, TNF-${\alpha}$ and LPS + TNF-${\alpha}$-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control, respectively. The $NF-{\kappa}B$ inhibitor also inhibited significantly LPS and SNP-induced expression of $NF-{\kappa}B$ dependent luciferase activity compared with control. Conclusions : These results suggest the inhibitory action of bee venom and melittin solution on the inflammatory mediators such as $PEG_2$, COX-2 and $NF-{\kappa}B$.

• BMB Reports
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• 제35권3호
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• pp.337-342
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• 2002

Many components that are derived from medicinal or dietary plants possess potential chemopreventive properties. Curcumin, a yellow coloring agent from turmeric (Curcuma longa Linn, Zingiberaceae), possesses strong antimutagenic and anticarcinogenic activities. In this study, we have found that curcumin inhibits the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear factor ${\kappa}B$ (NF-${\kappa}B$) activation by preventing the degradation of the inhibitory protein $I{\kappa}B{\alpha}$ and the subsequent translocation of the p65 subunit in cultured human promyelocytic leukemia (HL-60) cells. Alternatively, curcumin repressed the TPA-induced activation of NF-${\kappa}B$ through direct interruption of the binding of NF-${\kappa}B$ to its consensus DNA sequences. Likewise, the TPA-induced DNA binding of the activator protein-1 (AP-1) was inhibited by curcumin pretreatment.

• 동의생리병리학회지
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• 제26권6호
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• pp.922-928
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• 2012

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is one of the most abundant isothiocyanates in some cruciferous vegetables, especially broccoli. Sulforaphaene has been shown to exhibit many pharmacological activities, including anti-oxidant, anti-inflammatory and anti-microbial activities. However, the anti-skin photoaging effects of sulforaphane have not yet been reported. In the present study, we investigated the inhibitory effects of sulforaphane on MMP-1 and -3 expressions of the human dermal fibroblasts via various in vitro experiments and elucidated the pathways of inhibition. Western blot analysis and real-time PCR revealed sulfiraphane inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, which was determined by NF-${\kappa}B$ DNA binding activity. UVB-induced NF-${\kappa}B$ activation and MMP expression were completely blocked by sulforphane. These findings suggest that sulforaphane could prevent UVB-induced MMPs expressions through inhibition of NF-${\kappa}B$ activation.

• 한국한의학연구원논문집
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• 제16권3호
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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.

• 대한한방소아과학회지
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• 제24권1호
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• pp.93-103
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• 2010

Objectives The purpose of this study was to examine the pathway of anti-allergic effects of Cheonmaec-tang (CMT). Methods We examined the cell viability, $\beta$-hexosaminidase release, pro-inflammatory cytokines secretion and mRNA expressions, nuclear factor-kappa B (NF-${\kappa}B$) (p65) activation, inbibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) degradation, and MAPKs activation in RBL-2H3 cells pre-treated by CMT of 2.0 mg/ml, 4.0 mg/ml separately. Results We observed that CMT reduced the secretion of $\beta$-hexosaminidase, TNF-$\alpha$, IL-4 and the expression of COX-2 mRNA in RBL-2H3 cells. Furthermore, CMT 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 CMT has an anti-histamine effect and inhibitory effect of NF-${\kappa}B$ (p65) through regulation of $I{\kappa}B-{\alpha}$ degradation. These suggest that CMT could be used as an anti-allergic medicine.

• 대한화장품학회지
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• 제42권4호
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• pp.311-320
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• 2016

카바(Piper methysticum, P. methysticum)는 비뇨생식기 질환, 류머티즘, 위장 장애, 호흡기 자극 및 폐 통증에 대해 전통적으로 사용되는 것으로 알려져 있다. 본 연구에서는 카바에서 분리된 flavokavain C (FKC)가 염증성 유전자의 발현에 관여하는 전사인자인 핵요소-${\kappa}B$ (NF-${\kappa}B$) 의존성 산화 질소(NO) 생산 및 산화 질소 합성 효소(iNOS)의 발현에 리포폴리사카라이드(LPS) 처리된 대식세포에서 항 염증 활성을 나타낸다는 것을 확인하였다. FKC는 과산화수소와 같은 반응성 산소 종(ROS)의 축적을 억제하고, LPS로 유도된 NO 생성 및 각종 염증 관련 유전자(iNOS, IL-$1{\beta}$, IL-6)의 발현을 NF-${\kappa}B$ 및 MAPKs (ERK 및 JNK)의 억제를 통해 농도 의존적으로 줄일 수 있었다. 결론적으로, 이러한 결과는 FKC가 NF-${\kappa}B$ 경로와 MAPKs 포함한 염증 프로세스를 억제하는 능력을 가지고 있음을 나타내며, 이는 항 염증 및 항산화 효능 기반 기능성 화장품에 적용될 수 있음을 암시한다.

• BMB Reports
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• 제36권1호
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• pp.66-77
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• 2003

Tea is one of the most popular beverages consumed in the world and has been demonstrated to have anti-cancer activity in animal models. Research findings suggest that the polyphenolic compounds, (-)-epigallocatechin-3-gallate, found primarily in green tea, and theaflavin-3,3'-digallate, a major component of black tea, are the two most effective anti-cancer factors found in tea. Several mechanisms to explain the chemopreventive effects of tea have been presented but others and we suggest that tea components target specific cell-signaling pathways responsible for regulating cellular proliferation or apoptosis. These pathways include signal transduction pathways leading to activator protein-1 (AP-1) and/or nuclear factor kappa B(NF-${\kappa}B$ ). AP-1 and NF-${\kappa}B$ are transcription factors that are known to be extremely important in tumor promoter-induced cell transformation and tumor promotion, and both are influenced differentially by the MAP kinase pathways. The purpose of this brief review is to present recent research data from other and our laboratory focusing on the tea-induced cellular signal transduction events associated with the MAP kinase, AP-1, and NF-${\kappa}B$ pathways.

• 대한한방내과학회지
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• 제28권3호
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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.