• Toxicological Research
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• 제22권1호
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• pp.31-37
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• 2006

It was previously found that melittin inhibited $NF-{\kappa}B$ activity by reacting with signal molecules of $NF-{\kappa}B$ which is critical contributor in cancer cell growth by induction of apoptotic cell death. We here investigated whether melittin inhibits cell growth of human prostate cancer cells through induction of apoptotic cell death, and the possible signal pathways. Melittin ($0{\sim}1\;{\mu}g/ml$) inhibited prostate cancer cell growth in a dose dependent manner. Conversely related to the growth inhibitory effect, melittin increased the induction of apoptotic cell death in a dose dependent manner. Melittin also inhibited DNA binding activity of $NF-{\kappa}B$, an anti-apoptotic transcriptional factor. Consistent with the induction of apoptotic cell death and inhibition of $NF-{\kappa}B$, melittin increased the expression of pro-apoptotic proteins caspase-3, and Bax but down-regulated anti-apoptotic protein Bcl-2. These findings suggest that melittin could inhibit prostate cancer cell growth, and this effect may be related with the induction of apoptotic cell death via inactivation of $NF-{\kappa}B$.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.123-132
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• 2005

Melittin,cationic 26-amino acid, is the principal component of the bee venom (BV) which has been used for treatment of inflammatory disease such as arthritis rheumatism NF-kB is activated by subsequent release of inhibitory IkB via activation of a multisubunit IkB kinase (IKK). We previously found that melittin bind to the sulfhydryl group of p50, a subunit of NF-kB. Since sulfhydryl group is present in kinase domain of IKKa and IKKb, melittin could modify IKK activity by protein-protein interaction. We therefore examined effect of melittin on IKK activities in sodium nitroprusside (SNP)-stimulated synoviocyte obtained from RA patients. Melittin suppressed the SNP-induced release of IkB resulted in inhibition of DNA binding activity of NF-kB and NF-kB-dependent luciferase activity. Consistent with the inhibitory effect on NF-kB activation, IKKa and IKKb activities were also suppressed by melittin. Surface plasmon resonance analysis realized that melitin binds to IKKa $(Kd\;=\;1.34{\times}10-9M)$ and IKKb$(Kd\;=\;1.0{\times}10-9M)$. Inhibition of IKKa and IKKb resulted in reduction of the SNP-induced production of inflammatory mediators NO and PGE2 generation. The inhibitory effect of melittin on the IKKs activities, binding affinity of melittin to IKKs, and NO and PGE2 generation were blocked by addition of reducing agents dithiothreitol and glutathione. In addition, melittin did not show inhibitory effect in the transfected Synoviocytes with plasmid carrying dominant negative mutant IKKa (C178A) and IKKb (C179A). These results demonstrate that melittin directly binds to sulfhydryl group of IKKs resulting in IkBrelease, thereby inhibits activation of NF-kB and expression of genes involving in the inflammatory responses.

• Biomolecules & Therapeutics
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• 제22권1호
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• pp.55-61
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• 2014

Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-${\kappa}B$ and the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides $Rk_3$ and $Rs_4$ exerted the strongest activity, inhibiting NF-${\kappa}B$ in a dose-dependent manner. SF and $Rg_6$ also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-${\alpha}$-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-${\alpha}$-mediated diseases such as chronic hepatic inflammation.

• 동의생리병리학회지
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• 제22권2호
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• pp.385-389
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• 2008

Nitric oxide (NO) has been suggested to play an important role in endotoxin-mediated shock and inflammation. In this study, we investigated the effect of Rosa laevigata Michx. (Rosaceae) on the production of NO and the molecular mechanism of its action. Rosa laevigata inhibited NO generation and iNOS expression in LPS-stimulated murine macrophages. Activity of nuclear $factor{-\kappa}B\;(NF{-\kappa}B)$ and the degradation of $I{\kappa}B-{\alpha}$ were suppressed by Rosa laevigata. Furthermore, extracellular signal-stimulated kinase (ERK), which is known to be involved in $NF{-\kappa}B$ activation, is inhibited by Rosa laevigata. These results suggest that Rosa laevigata could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of $NF{-\kappa}B$ activity.

• 생약학회지
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• 제35권1호통권136호
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• pp.92-97
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• 2004

Effect of AGI $({\alpha}-Glucosidase\;Inhibitor)-1120$, pine (Pinus densiflora) bark extract and Chaga mushroom (Inonotus obliquus) - and Chaga mushroom mycelium extracts on cellular $NF-{\kappa}B$ activation in malignant human keratinocytes (SCC-13) were evaluated to elucidate the possible correlation of $NF-{\kappa}B$ with antioxidant activity. The antioxidant activities of these natural products were examined in three different evaluation methods, i.e., lipid peroxidation value (POV) evaluation test, and 1,1diphenyl-2-picrylhydrazyl radical (DPPH) and nitric oxide (NO) scavenging test. In a cell-based $NF-{\kappa}B$ monitoring assay systern, all samples revealed the downregulatory profiles on the cellular $NF-{\kappa}B$ activity. AGI -1120 (1, 2 mg) and Chaga mushroom extract (0.05, 0.1 mg) downregulated the $NF-{\kappa}B$ activity in a dose-dependent manner. Chaga mushroom mycelium extract (5 mg) significantly inhibited the $NF-{\kappa}B$ activity (p<0.05). Although AGI-1120 and Chaga mushroom mycelium extract exhibited no antioxidant activities evaluated in pay, Chaga mushroom extract showed antioxidant in a dose-dependent manner at concentrations of $0.05{\sim}1$ mg. While AGI-1120 and Chaga mushroom extract possessed a relatively potential DPPH radical scavenging activity, the NO scavenging activity of Chaga mushroom extract $(SC_{50}:47\;{mu}g)$ was higher than the known antioxidant, vitamin C $(SC_{50}:77\;{mu}g)$. These results suggest that AGI-1120 and Chaga mushroom- and Chaga mushroom mycelium extracts may serve as an useful radical scavenging antioxidant agents with $NF-{\kappa}B$ inhibitory effect in human skin.

• 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.

• 약학회지
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• 제57권6호
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• pp.426-431
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• 2013

In our previous studies, 6-hydroxy-7-methoxychroman-2-carboxylic acid N-phenylamide (KL-1156) was identified as a good inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation. In continuation of our study, we describe the structure-activity relationship of chroman derivatives containing N-arylalkyl groups and their NF-${\kappa}B$ inhibitory activities. In addition, inhibitory effects of cell proliferation are evaluated against human cancer cell lines (NCI-H23 and PC-3). The most active compounds 3i and 3j contained diphenylethyl and diphenylpropyl side chain on amide nitrogen.

• 한국임상수의학회지
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• 제28권2호
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• pp.190-195
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• 2011

본 연구에서 돼지 PBMC에 t10c12-CLA 처리는 TNF-${\alpha}$생산을 증가시켰으나, LPS 자극 PBMC에서는 TNF-${\alpha}$생산을 감소시켰다. t10c12-CLA 처리는 PBMC의 inhibitory ${\kappa}B$ ($I{\kappa}B$)-${\alpha}$ 단백질 분해를 증가시키고 NF-${\kappa}B$ p65 활성 수준을 증가시켰다. 그러나 LPS 자극 PBMC에서는 상반되는 효과가 관찰되었다. 특히, LPS 비자극 PBMC에서 t10c12-CLA는 NF-${\kappa}B$ 저해제인 caffeic acid phenethyl ester (CAPE)를 처리한 경우 NF-${\kappa}B$ p65 활성 수준을 증가시켰으나 반대로 LPS로 자극한 CAPE 처리 PBMC에서는 NF-${\kappa}B$ p65 활성 수준을 억제시켰다. 이상의 결과는 t10c12-CLA가 돼지 PBMC에 있어 LPS 자극 유무에 따라 다른 효과를 가질 수 있으며, 이는 NF-${\kappa}B$ p65 활성도의 변화와 관련성이 있음을 보여주고 있다.

• BMB Reports
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• 제41권4호
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• pp.328-333
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• 2008

A variety of anti-inflammatory agents have been shown to exert chemopreventive activity via targeting of transcription factors such as NF-${\kappa}B$ and AP-1. Lithospermum erythrorhizon (LE) has long been used in traditional oriental medicine. In this study, we demonstrated the inhibitory effects of LE extracts on lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines. As an underlying mechanism of inhibition, LE extracts reduced LPS-induced transactivation of AP-1 as well as NF-${\kappa}B$ in mouse macrophage cells. Electrophoretic mobility shift assays indicated that LE extracts inhibited the DNA binding activities of AP-1 and NF-${\kappa}B$. In addition, phosphorylation of $I{\kappa}B-{\alpha}$ protein was suppressed by LE extracts. Moreover, LE extracts inhibited c-Jun N-terminal kinase and extracellular signal-regulated signaling pathways. Our results suggest that the anti-inflammatory activity of LE extracts may be mediated by the inhibition of signal transduction pathways that normally lead to the activation of AP-1and NF-${\kappa}B$. These inhibitory effects may be useful for chemoprevention of cancer or other chronic inflammatory diseases.

• 한국임상수의학회지
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• 제29권5호
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• pp.361-367
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• 2012

고혈당으로 야기된 염증은 당뇨병에서 합병증을 일으키는 주된 요인이다. 최근 연구에 따르면 면역세포에서 TNF-${\alpha}$ 같은 염증성 cytokine의 과도한 생성은 인슐린 저항성을 야기시킨다고 한다. Conjugated linoleic acid (CLA)는 TNF-${\alpha}$ 생산에 관여하여 면역반응을 조절하는 것으로 알려져 있다. 본 연구는 고농도의 당으로 처리한 RAW 264.7 세포에서 TNF-${\alpha}$ 생산, NF-${\kappa}B$의 활성과 $I{\kappa}B-{\alpha}$ 분해에 대한 CLA 효과를 검토하였다. 고농도의 당에 노출된 RAW세포는 저농도의 당에 노출된 RAW 세포보다 NF-${\kappa}B$의 활성과 $I{\kappa}B-{\alpha}$ 분해가 증가되었으며 RAW 세포의 배양 상층액 중에 TNF-${\alpha}$ 생산을 증가시켰다. CLA와 고농도 또는 저농도의 당을 같이 처리한 군은 당만 단일 처리한 군보다 TNF-${\alpha}$ 생산, NF-${\kappa}B$의 활성 및 $I{\kappa}B-{\alpha}$ 분해가 증가되었다. 그리고 고농도의 당과 CLA를 처리한 군에서 저농도의 당과 CLA 처리군에 비해 NF-${\kappa}B$의 활성과 $I{\kappa}B-{\alpha}$ 분해가 증가되었으며 이와 더불어 TNF-${\alpha}$의 양이 증가되었다. 이상의 결과로부터, CLA는 고농도의 당에 노출된 RAW 세포에서 NF-${\kappa}B$의 활성을 높이고 TNF-${\alpha}$ 생산을 증가시키며 이는 고혈당으로 유발되는 염증반응을 촉진하는 인자로 작용할 수 있음을 시사하였다.