• BMB Reports
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• 제42권5호
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• pp.265-270
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• 2009

Due to their multiple biological activities, flavonoids have gained attention as potentially useful therapeutics for a variety of diseases including cancer, cardiovascular diseases, and autoimmune diseases. In this study, we demonstrated that several flavonoids, including kaempferol, quercetin, fisetin, and chrysin block TNF-$\alpha$ induced IL-8 promoter activation and gene expression in HEK 293 cells. In addition, phosphorylation and degradation of $I{\kappa}B{\alpha}$ and translocation of NF-${\kappa}B$ p65 were inhibited by these flavonoids in TNF-$\alpha$-stimulated HEK 293 cells. Furthermore, generation of reactive oxygen species (ROS) in response to TNF-$\alpha$ was reduced by the flavonoids. Moreover, although pretreatment with fisetin, quercetin, or chrysin decreased cell viability, kaempferol did not. Taken together, these findings suggest that kaempferol would be useful for the treatment of TNF-$\alpha$-induced inflammatory diseases.

• 동의생리병리학회지
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• 제22권5호
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• pp.1315-1321
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• 2008

본 논문은 오랫동안 민간요법으로 염증치료에 사용되어오던 섬수가 lipopolysaccharide(LPS)-자극된 BV2 소교 세포의 nitric oxide(NO) 분비에 미치는 효과에 대해 연구한 내용이다. 실험 결과 섬수는 세포 생존력에 대한 영향 없이 BV2 소교 세포에서 NO 분비를 억제시켰고, nitric oxide synthase (iNOS) 단백질도 감소시켰다. 또한 섬수는 prostaglandin E2 (PGE2) 생산 및 cyclooxygenase (COX)-2 발현을 저지하였고, proinflammatory cytokines과 ${IkB-\alpha}$감소를 억제시켰다. 따라서 섬수가 $I{\kappa}B-{\alpha}$감소를 억제함으로써 NO 합성을 저해하여 항염증작용을 할 수 있다는 내용이다.

• 한국식품영양과학회지
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• 제41권9호
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• pp.1226-1234
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• 2012

본 연구에서는 염증반응을 조절하는 다양한 신호전달체계를 중심으로 분자생물학적 방법을 통해 piceatannol의 항염증 기전을 규명하였다. LPS로 염증반응을 유도한 Raw 264.7 대식세포에서 piceatannol은 iNOS의 발현 억제를 통해 NO의 생성을 감소시키고 염증성 사이토카인(TNF-${\alpha}$, IL-6, IL-$1{\beta}$)의 생성을 감소시켰다. 염증반응을 조절하는 신호전달체계 중 piceatannol은 LPS에 의해 유도된 $I{\kappa}B$의 분해와 p65의 핵으로의 이동을 억제하고, LPS에 의해 유도된 SAPK/JNK의 인산화를 억제하였다. 또한 piceatannol은 LPS와 IL-6(LPS에 의해 증가됨)에 의한 STAT3의 활성화를 억제하였다. 뿐만 아니라 piceatannol은 Nrf2의 핵 내 축적을 야기하고 ARE의 transcriptional activity를 증가시켜 HO-1의 발현을 증가시켰다. 본 연구의 결과, piceatannol은 NF-${\kappa}B$와 AP-1, STAT3 신호전달의 억제를 통해, 그리고 HO-1의 발현 증가를 통해 항염증 효과를 나타내었다(Fig. 8).

• 한방안이비인후피부과학회지
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• 제23권2호
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• pp.13-26
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• 2010

Objectives : The present study was conducted to evaluate the anti-inflammatory effects of the Gamroeum water extracts (GRE) in vivo and in vitro. Methods : The effects of GRE on anti-inflammation were measured by production of NO, $PGE_2$ (Prostaglandin $E_2$), iNOS (inducible Nitric Oxide Synthase), COX-2, $NF{\kappa}B$ (Nuclear Factor kappa B), TNF-$\alpha$ (Tumor Necrosis Factor-alpha) and IL-$1{\beta}$ (Interleukin-$1{\beta}$), IL-6 in Raw 264.7 macrophage cells stimulated with LPS. Results : 1. In machrophage cells, LPS displayed significant stimulatory effects on the production of NO and $PGE_2$. However, GRE showed significant inhibitory effects on NO and $PGE_2$ release. The level of NO and $PGE_2$ was decreased by GRE in a concentration dependent manner as compared with LPS only group. 2. Immunoblot analysis verified that LPS stimulation significantly increased the iNOS and COX-2 protein level, but GRE suppressed the induction of iNOS and COX-2 protein at a concentration dependent manner. 3. GRE reduced the elevated production of TNF-$\alpha$, IL-$1{\beta}$ and IL-6 by LPS. Moreover, the inhibitory effects of GRE was occurred in a dose-dependent manner. 4. GRE significantly reduced the expression of NF-${\kappa}B$ protein in nuclear fraction. 5. GRE effectively inhibited the increases of hind paw skin thicknesses and inflammatory cell infiltrations induced by carrageenan treatment. It, therefore, considered that GRE will be favorably inhibited the acute edematous inflammations. Conclusions : These results indicated that GRE could have anti-inflammatory capacity by inhibiting the production of NO, $PGE_2$ and cytokines in vitro and by reducing the formation of carrageenan-induced paw edema in vivo. Moreover, inhibitory effects of GRE on the macrophage activation were attributable to the reduction of some of inflammatory factors by inhibiting iNOS and COX-2 through the suppression of NF-${\kappa}B$.

• 생명과학회지
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• 제23권4호
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• pp.501-509
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• 2013

포름알데히드는 주로 산업용으로 사용되는 독성이 강한 물질로서 생체에 노출 시 염증, 산화적 스트레스, 알레르기 반응, 나아가서 암을 유발하게 된다. 불가사리에서 추출되는 saponin은 sulphated sterol glycosides 등으로서 인삼 saponin (ginsenoside)들과 화학적 구조가 비슷하여 항균 및 세포독성을 비롯한 미생물을 괴사시키는 기능을 가지고 있음이 보고되었다. 또한 손상된 불가사리의 조직에는 염증성 사이토카인이 발현되는데 TGF-${\beta}$의 증가로 손상 받은 부위를 빠르게 치료, 재생하게 된다. 본 실험은 조직손상 후 8일 된 불가사리 추출물과 포름알데히드를 IMR-90에 처리했을 때와 포름알데히드에 노출시킨 ICR 마우스에 불가사리 추출물을 흡입시켰을 때 염증성 폐 손상의 방어 및 치료에 미치는 효과를 알아보았다. 포름알데히드에 노출된 IMR-90에 조직손상 후 8일이 경과한 불가사리 추출물을 처리한 결과, 세포의 유의한 증식을 보였으며 염증 조절에 영향을 주는 TNF-${\alpha}$, NF-${\kappa}B$의 발현억제 및 $I{\kappa}-B{\alpha}$의 합성을 촉진시켰다. 포름알데히드에 노출된 ICR 마우스에 조직손상 후 8일이 경과한 불가사리 추출물을 처리한 군에서 체중의 증가, 항산화 효소의 증가, 지질과산화 작용의 감소, surfactant protein A의 증가, TNF-${\alpha}$ 및 NF-${\kappa}B$의 발현억제, $I{\kappa}-B{\alpha}$ 발현의 증가와 조직재생에 우수한 효과를 보였다. 이러한 결과는 포름알데히드로 인한 세포 및 폐 손상을 불가사리 추출물의 항염증 작용을 통하여 억제하거나 완화시킴을 확인할 수 있다.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.383-389
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• 2017

Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

• Journal of Periodontal and Implant Science
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• 제43권4호
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• pp.191-197
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• 2013

Purpose: Nitric oxide (NO) is a short-lived bioactive molecule that is known to play an important role in the pathogenesis of periodontal disease. In the current study, we investigated the effect of the flavonoid quercetin on the production of NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen related to inflammatory periodontal disease, and tried to elucidate the underlying mechanisms of action. Methods: LPS was isolated from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The concentration of NO in cell culture supernatants was determined by measuring the accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38, inhibitory ${\kappa}B$ $(I{\kappa}B)-{\alpha}$ degradation, and signal transducer and activator of transcription 1 (STAT1) phosphorylation were analyzed via immunoblotting. Results: Quercetin significantly attenuated iNOS-derived NO production in RAW246.7 cells activated by P. intermedia LPS. In addition, quercetin induced HO-1 protein expression in cells activated with P. intermedia LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The degradation of $I{\kappa}B-{\alpha}$ induced by P. intermedia LPS was inhibited when the cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1 signaling. Conclusions: Quercetin significantly inhibits iNOS-derived NO production in murine macrophages activated by P. intermedia LPS via anti-inflammatory HO-1 induction and inhibition of the nuclear factor-${\kappa}B$ and STAT1 signaling pathways. Our study suggests that quercetin may contribute to the modulation of host-destructive responses mediated by NO and appears to have potential as a novel therapeutic agent for treating inflammatory periodontal disease.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.107-112
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• 2012

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as neuronal protection against excitotoxicity and anti-inflammatory property, the biological activity of 3,4,5-trihydroxycinnamic acid (THC), a derivative of hydroxycinnamic acids, has not been clearly examined. The objective of the present study is to evaluate the anti-inflammatory effects of THC on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. THC significantly suppressed LPS-induced excessive production of nitric oxide (NO) and expression of iNOS, which is responsible for the production of iNOS. THC also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$and TNF-${\alpha}$ in BV2 microgilal cells. Furthermore, THC significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm. Therefore, THC attenuated nuclear translocation of NF-${\kappa}B$, a major pro-inflammatory transcription factor. Taken together, the present study for the first time demonstrates that THC exhibits antiinflammatory activity through the suppression of NF-${\kappa}B$ transcriptional activation in LPS-stimulated BV2 microglial cells.

• 대한본초학회지
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• 제27권1호
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• pp.59-64
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• 2012

Objective : This study was performed to evaluate the effect of Forsythiae Fructus (FF) ethanol extract on inflammatory cytokine production and its underlying mechanisms in mouse macrophages. Methods : Peritoneal macrophages from thioglycollate medium-injected mice were cultured and stimulated with lipopolysaccharide(LPS) or LPS/interferon(IFN)-${\gamma}$ for cytokine measurement and cellular signaling molecule analysis. Results : FF ethanol extract decreased the levels of secreted tumor necrosis factor(TNF)-${\alpha}$ and interleukin(IL)-6 in IFN-${\gamma}$/LPS-stimulated cells in a concentration-dependent manner. FF extract reduced IFN-${\gamma}$/LPS-induced STAT1 phosphorylation and LPS-induced p38 and JNK activation, but not ERK1/2 activity. The extract also inhibited LPS-induced $I{\kappa}B{\alpha}$ degradation through suppression of $I{\kappa}B{\alpha}$ kinase. Conclusions : These results suggest that FF ethanol extract affects the production of TNF-${\alpha}$ and IL-6 through inhibition of activation of STAT-1, $I{\kappa}B{\alpha}$, p38, and JNK.

• 대한한방부인과학회지
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• 제32권3호
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• pp.20-31
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• 2019

Objectives: The seeds from Arctium lappa have been considered for its various pharmacological properties, which include anti-carcinogenic, anti-inflammatory, anti-diabetic, and anti-viral activities. Methods: In the present study, we investigated the anti-inflammatory effect of the ethanol extract from the seeds of Arctium lappa L (EAL) on cytokine-induced vascular inflammation in human umbilical vein endothelial cells (HUVEC). Results: Pretreatment with EAL significantly decreased tumor necrosis factor alpha ($TNF-{\alpha}$)-induced cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) in a dose-dependent manner. Cell adhesion assay showed that pretreatment with EAL suppressed HUVEC-monocyte adhesion by $TNF-{\alpha}$ over $1{\mu}g/ml$ concentration. We investigated the involvement of nuclear transcription factor kappa-B ($NF-{\kappa}B$) in $TNF-{\alpha}$-induced vascular inflammation. $NF-{\kappa}B$ p65 nuclear expression was induced by $TNF-{\alpha}$, however, pretreatment with EAL was attenuated that nuclear translocation. In cytoplasm, EAL was also attenuated $TNF-{\alpha}$-induced decrease of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$) expression. Moreover, EAL significantly decreased $TNF-{\alpha}$-induced production of intracellular reactive oxygen species (ROS). Conclusions: Taken together, our findings suggest that seeds of Arctium lappa L could be a therapeutic herb for prevention of cardiovascular diseases throughout the inhibition of vascular endothelial inflammation.