• 동의생리병리학회지
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• 제26권3호
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• pp.293-300
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• 2012

Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important inflammatory mediators implicated in pathogenesis of inflammation and certain types of human cancers. The present study was designed to determine whether Red Ginseng (RG) could modulate $I{\kappa}B$-kinase, iNOS and COX-2 gene expression and immune responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). RG extract suppressed the expression of LPS-induced $I{\kappa}B$, iNOS, COX-2, and immune responses in a dose-dependent manner. It also showed an anti-inflammatory effect by inhibiting NF-${\kappa}B$ immune response induced by LPS treatment. Inhibitory effect of RG on LPS-induced inflammation was mediated by suppressed phosphorylation of ERK, JNK and p38 through the regulation of the mitogen-activated protein kinase (MAPK) pathway leading to a decreased production of NO, iNOS, COX-2 and NF-${\kappa}B$. The results implied the role of RG as an inflammation regulator and its possible application for curing inflammatory diseases.

• 생약학회지
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• 제39권2호
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• pp.95-103
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• 2008

In the present study, we investigated the anti-inflammatory effects by kaempferol-3-O-${\beta}$-D-sophoroside (KS) isolated from Sophora japonica (Leguminosae) on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin ($PGE_2$) production by RAW 264.7 cell line compared with kaempferol. KS significantly inhibited the LPS-induced NO and $PGE_2$ production. Consistent with these observations, KS reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner. In addition, the release and the mRNA expression levels of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-6 (IL-6) were also reduced by KS. Moreover, KS attenuated the LPS-induced activation of nuclear factor-kappa B ($NF{-\kappa}B$), a transcription factor necessary for pro-inflammatory mediators, iNOS, COX-2, $TNF-{\alpha}$ and IL-6 expression. These results suggest that the down regulation of iNOS, COX-2, $TNF-{\alpha}$, and IL-6 expression by KS are achieved by the downregulation of $NF{-\kappa}B$ activity, and that is also responsible for its anti-inflammatory effects.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8411-8418
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• 2016

The effect of Eruca sativa seed extract (SE) on nuclear factor kappa B (NF-${\kappa}B$), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels was investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(${\alpha}$)anthracene (DMBA). DMBA increased NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while, decreased glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. After DMBA administration, SE treatment reduced NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and LP. Hence, SE treatment reduced inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC. Analysis revealed that SE has high concentrations of total flavonoids, triterpenoids, alkaloids and polyphenolic compounds such as gallic, chlorogenic, caffeic, 3,4-dicaffeoyl quinic, 3,5-dicaffeoyl quinic, tannic, cinnamic acids, catechin and phloridzin. These findings indicate that SE may be considered a promising natural product from cruciferous vegetables against breast cancer, especially given its high antioxidant properties.

• 생명과학회지
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• 제20권3호
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• pp.388-395
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• 2010

본 연구에서는 콩 발효 산물 추출물의 항염증 효능에 관한 기초 자료를 제시하기 위하여 PMA에 의해 유도되는 COX-2의 발현 및 $PGE_2$의 생성 증가에 미치는 이들 추출물의 영향을 조사하였다. 본 연구에서 조사된 3가지 콩 발효 산물은 PMA에 의한 COX-2의 발현 증가를 매우 유의적으로 차단하였으며, 이는 $PGE_2$의 생성 억제와 연관성이 있었다. 아울러 PMA에 의한 NF-${\kappa}B$ 활성 증가 또한 콩 발효 산물들에 의하여 유의적으로 억제되었다. 이러한 결과들은 콩 발효 산물에 의한 NF-${\kappa}B$ 활성의 억제가 COX-2의 발현을 저하시켰으며, 이로 인한 $PGE_2$의 생성이 억제된 것으로 추정되어진다. 이러한 콩 발효 산물의 항염증 효과는 대두 추출물보다 아가콩 추출물에서 더욱 효과가 높게 나타났으며, 이는 향후 아가콩 추출물은 염증성 질환 예방/치료를 위한 적용 가능성이 매우 우수함을 제시하여 주는 결과이다.

• Food Science and Biotechnology
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• 제15권2호
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• pp.303-307
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• 2006

Effect of Oenanthe javanica ethanol extract (OJE) on nuclear factor-${\kappa}B$ (NF-${\kappa}B$)-mediated inflammatory reaction in RAW 264.7 macrophage cells was investigated. The OJE dose-dependently inhibited secretions of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandins $E_2\;(PGE_2)$ from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and blocked LPS-induced expression of cyclooxygenase-2. To clarify mechanistic basis for its inhibitions of NF-${\kappa}B$ and activator protein-1 (AP-1) activations, effects of OJE on activations of NF-${\kappa}B$ and AP-1 genes by luciferase reporter activity were examined. The LPS-stimulated activations of NF-${\kappa}B$ and AP-1 were significantly blocked by 400 and $600\;{\mu$}g/mL of OJE, implicating that OJE might regulate gene expression through more than one signaling pathway. Cytosolic degradation of I-${\kappa}B{\alpha}$ was inhibited by OJE dose-dependently, indicating that the nuclear translocation of p65 was inhibited by OJE. These findings suggest that the inhibition of LPS-stimulated COX-2 expression by OJE is due to its inhibition of NF-${\kappa}B$ activation by blocking I-${\kappa}B{\alpha}$ degradation, which may be mechanistic basis of anti-inflammatory effects of OJE.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.95.1-95
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• 2003

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.

• Natural Product Sciences
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• 제10권6호
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• pp.315-320
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• 2004

Alpha-viniferin was previously isolated as a cyclooxygenase (COX)-2 inhibitor from Carex humilis (Cyperaceae) and is an oligomeric stilbene compound with benzofuran (BF) moieties in its chemical structure. In the present study, a chemically synthetic BF compound, named as 3,3-dimethyl-2,3,4,6,7,8,9,10,11,12,13,14,15,16,17,18-hexadecahydro-1H-benzo[b] cyclopentadeca[d]furan-1-one, was discovered to inhibit bacterial lipo polysaccharide (LPS)-induced prostaglandin $E_2$ $(PGE_2)$ production in macrophages RAW 264.7. The BF compound exhibited a selectively preferred inhibitory effect on COX-2 activity over COX-1 activity. Furthermore, BF compound inhibited LPS-induced COX-2 expression at transcription level. As a down-regulatory mechanism of COX-2 expression shown by BF compound, suppression of nuclear factor $(NF)-{\kappa}B$ activation has been demonstrated. BF compound inhibited LPS-induced $NF-{\kappa}B$ transcriptional activity and nuclear translocation of $NF-{\kappa}B$ p65, in parallel, but did not affect LPS-induced degradation of inhibitory ${\kappa}B{\alpha}$ protein $(I{\kappa}B{\alpha})$. Taken together, anti-inflammatory effect of BF compound on $PGE_2$ production was ascribed by its down-regulatory action on LPS-induced COX-2 synthesis in addition to inhibitory action on enzyme activity of COX-2.

• 생명과학회지
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• 제20권8호
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• pp.1221-1229
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• 2010

정상세포뿐 만 아니라 형질 전환된 세포의 증식조절에 중요한 역할을 하는 것으로 알려진 COX-2는 전사조절인자인 NF-${\kappa}B$에 의해서 조절되며, 염증반응에 있어서 중요한 역할을 하는 PGE2의 생성에 관여하는 것으로 알려져 있다. 본 연구에서는 U937 인체혈구세포에서 염증유발인자인 PMA에 의해서 유발되는 염증반응에 있어서 중요한 역할을 하는 COX-2 및 COX-2의 산물인 PGE2와 COX-2의 발현에 영향을 미치는 전사조절인자인 NF-${\kappa}B$의 발현에 협죽도 잎 및 줄기의 에탄올 추출물인 ENIL 및 ENIS가 어떠한 영향을 미치는 지를 조사하였다. PMA가 처리된 U937 세포에서 COX-1의 발현에는 아무런 영향을 미치지 못하였지만 COX-2의 발현 증가가 유도되었고 이에 따른 PGE2의 생성이 증가되었다. PMA에 의해서 증가된 COX-2의 발현이 ENIS 선처리에 의하여 거의 완벽하게 억제되었고 그에 따른 PGE2의 생성도 현저하게 감소되었다. ENIS에 의한 COX-2의 발현 및 PGE2의 생성억제가 전사조절인자인 NF-${\kappa}B$와 상관성이 있는지를 조사한 결과, 핵 내로의 NF-${\kappa}B$ 이동이 ENIS 선처리에 의하여 억제되는 것으로 나타났다. 이는 ENIS가 NF-${\kappa}B$의 활성 억제를 통하여 COX-2의 발현 및 PGE2의 생성을 효과적으로 억제함으로서 항염증 효능을 가진다는 것을 의미하는 결과이다. 하지만 ENIL의 경우에는 이상에서와 같은 이러한 변화들이 매우 약하게 나타나는 것으로 조사되어 ENIS와 비교해서 항염증 효능이 낮은 것으로 나타났다. 본 연구 결과는 협죽도의 항염증기전에 대한 생화학적 해석 및 이를 활용한 향후 지속적인 연구를 위한 귀중한 자료가 될 것으로 생각된다.

• Journal of Ginseng Research
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• 제36권2호
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• pp.146-152
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• 2012

Panax ginseng (PG) is a globally utilized medicinal herb. The medicinal effects of PG are primarily attributable to ginsenosides located in the root and leaf. The leaves of PG are known to be rich in various bioactive ginsenosides, and the therapeutic effects of ginseng extract and ginsenosides have been associated with immunomodulatory and anti-inflammatory activities. We examined the effect of PG leaf extract and the isolated ginsenosides, on nuclear factor (NF)-${\kappa}B$transcriptional activity and target gene expression by applying a luciferase assay and reverse transcription polymerase chain reaction in tumor necrosis factor (TNF)-${\alpha}$-treated hepatocarcinoma HepG2 cells. Air-dried PG leaf extract inhibited TNF-${\alpha}$-induced NF-${\kappa}B$transcription activity and NF-${\kappa}B$-dependent cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) gene expression more efficiently than the steamed extract. Of the 10 ginsenosides isolated from PG leaves, Rd and Km most significantly inhibited activity in a dose-dependent manner, with $IC_{50}$ values of $12.05{\pm}0.82$ and $8.84{\pm}0.99\;{\mu}M$, respectively. Furthermore, the ginsenosides Rd and Km inhibited the TNF-${\alpha}$-induced expression levels of the COX-2 and iNOS gene in HepG2 cells. Air-dried leaf extracts and their chemical components, ginsenoside Rd and Km, are involved in the suppression of TNF-${\alpha}$-induced NF-${\kappa}B$ activation and NF-${\kappa}B$-dependent iNOS and COX-2 gene expression. Consequently, air-dried leaf extract from PG, and the purified ginsenosides, have therapeutic potential as anti-inflammatory.

• Food Science and Biotechnology
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• 제15권6호
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• pp.975-979
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• 2006

The extracts of Oenanthe javanica were evaluated for their effects on the expression of cyclooxygenase-2 (COX-2), which is mediated by the translocation of the p65 subunit into the nucleus. Fractions of ethyl acetate and chloroform from 80% ethanol extracts of O. javanica exhibited inhibitory effects on the secretion of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) from lipopolysaccharide (LPS)-stimulated peritoneal macrophages; however, the aqueous- and hexane-fractions showed no significant effect. The ethyl acetate- and chloroform-fractions also reduced the COX-2 enzyme levels after 24-hr treatment. RT-PCR showed that the mRNA levels of COX-2 decreased following treatment with these fractions, suggesting that COX-2 expression is transcriptionally regulated by these extracts. We examined the effects of the chloroform- and ethyl acetate-fractions on the cytosolic activation of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$, p65 subunit) and on the degradation of inhibitor-${\kappa}B{\alpha}$ ($I-{\kappa}B{\alpha}$) in order to determine the mechanism of COX-2 regulation. The LPS-stimulated activation of the p65 subunit was significantly blocked upon the addition of $50\;{\mu}g/mL$ of these fractions, and the cytosolic $I-{\kappa}B{\alpha}$ degradation process was simultaneously inhibited. These findings suggest that the inhibition of COX-2 expression by the ethyl acetate-and chloroform-fractions may result from the inhibition of p65 translocation by blocking the degradation of $I-{\kappa}B{\alpha}$; this may be the mechanistic basis for the anti-inflammatory effects of O. javanica.