• Advances in Traditional Medicine
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• 제10권1호
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• pp.37-43
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• 2010

Palmitic acid (PA) is one of free fatty acids, which is found from Gaultheria itoana Hayata and Sarcopyramis nepalensis. Although PA has a variety of pharmacological effects including mediates hypothalamic insulin resistance, induces IP-10 expression, and promote apoptotic activities, the anti-inflammatory mechanism of PA in mouse peritoneal macrophages remains unclear. In this study, we showed that PA exerted an anti-inflammatory action through suppression the production of tumor necrosis factor-$\alpha$, interleukin-6, cyclooxygenases-2 and nitric oxide in lipopolysaccaride-stimulated mouse peritoneal macrophages. Our study suggests an important molecular mechanism of PA, which might explain its beneficial effect in the regulation of inflammatory reactions.

• Biomolecules & Therapeutics
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• 제14권1호
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• pp.11-18
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• 2006

Certain flavonoids possess anti-inflammatory activity. Besides their antioxidative property, the cellular action mechanisms of flavonoids include an inhibition of arachidonate metabolizing enzymes such as cyclooxygenases and lipoxygenases, and a down-regulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-$\alpha$. In this review, the recent findings of anti-inflammatory flavonoid research since 2004 were summarized. And the cellular mechanisms on signal transduction pathways were also discussed.

• 동의생리병리학회지
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• 제22권2호
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• pp.415-421
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• 2008

Pro-inflammatory mediators, such as prostaglandin $E_2$ (PGE2), nitric oxide (NO), and cyclooxygenases-2 (COX-2), play pivotal roles in normal as well as transformed cells. Previous studies have shown that Euphorbiae humifusae Wind exhibits anti-proliferative and antioxidant activities. However, the it's anti-inflammatory properties are unclear. In this study, we examine the effects of water extract of E. humifusae (WEEH) on the expression of COX-2 and the production of $PGE_2$ in human lymphatic U937 cells. Treatment of phorbol 12-myristate-13-acetate (PMA) significantly induced COX-2 expression and $PGE_2$ production in U937 cells. However, pretreatment WEEH markedly inhibited the PMA-induced COX-2 expression and $PGE_2$ production in a dose-dependent manner. Moreover, WEEH prevented the elevated early growth response gene-1 (Egr-1) expression and nuclear factor-kappaB ($NF{-\kappa}B\; p65$) nuclear translocation stimulated by PMA treatment. Taken together, the present data indicate that WEEH exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the $NF{-\kappa}B$ and Egr-1 signaling pathway.

• Natural Product Sciences
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• 제18권4호
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• pp.211-214
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• 2012

Since 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key metabolic enzyme of prostaglandin $E_2$ ($PGE_2$), inhibition of 15-PGDH is supposed to facilitate various physiological functions by increasing $PGE_2$. Methanol extract of Artemisia argyi (AAME) inhibited 15-PGDH ($IC_{50}$: $13.13{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$: $415.00{\mu}g/mL$) and elevated extracellular $PGE_2$ levels in HaCaT cells. Real-time PCR analysis showed that AAME decreased significantly mRNA expression of PG transporter (PGT) in HaCaT cells. These results indicate that AAME could be applicable to functional materials as a 15-PGDH inhibitor and PGT expression inhibitor for the upregulation of extracellular $PGE_2$ level.

• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2011년도 춘계학술논문집 2부
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• pp.1068-1071
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• 2011

Cyclooxygenases (COX)-2 has been highly expressed in a variety of tumor cells and involved inflammatory process, tumor-associated angiogenesis, and vascular functions but the underlying mechanism is not clearly elucidated. We here investigated the molecular mechanism by which COX-2 regulates tumor-associated angiogenesis. In vivo, we injected B16-F1 cells overexpressed with COX-2 or mock in wild type or eNOS-deficient mice. Tumor cells overexpressed with COX-2 increase tumor-associated angiogenesis and tumor growth compared with control cells and that the effect of COX-2 was lower in eNOS-deficient mice than wild type mice. These results may contribute to further understanding of the regulation of angiogenesis by COX during tumor metastasis and inflammation.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.520-525
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• 2012

Prostaglandin (PG) $E_2$, the most abundant prostaglandin in the human body, is synthesized from arachidonic acid via the actions of cyclooxygenase (COX) enzymes. $PGE_2$ exerts homeostatic, cytoprotective, inflammatory, and in some cases anti-inflammatory effects. Also, it has been reported that $PGE_2$ is involved in hair growth. Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from the brown algae Ishige okamurae, with various biological activities in vitro and in vivo. In this study, the biological effect and mechanism of action of DPHC on prostaglandin synthesis in HaCaT human keratinocytes was examined. The results showed that, in these cells, DPHC significantly and dose-dependently induced $PGE_2$ synthesis by increasing the protein and mRNA levels of COX-1 and COX-2. Interestingly, DPHC-induced COX-1 expression preceded that of COX-2. Also, while both rofecoxib and indomethacin inhibited $PGE_2$ production, the latter was seems to be the more potent. From above results, we can expect that DPHC has some beneficial effects via increasing of $PGE_2$ production.

• Journal of Acupuncture Research
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• 제20권3호
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• pp.166-176
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• 2003

Objective : The aim of this study is to investigate the anti-inflammatory effects of 15Hz electroacupuncture(EA) on carrageenan-injected rats. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw. Methods : Bilateral EA stimulation with 15 Hz were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles for a total of 30 min duration in carrageenan-injected rats. Results: The developing edema was measured 30 minutes interval afer carrageenan injection and 15 Hz EA stimulation presented significant edema inhibition. Three hours after carrageenan injection, prostaglandin $E_2(PGE_2)$ and nitric oxide(NO) levels were measured. The 15Hz EA stimulation significantly inhibited $PGE_2$ and NO production in the right paw. The pro-inflammatory mRNA expression such as cyclooxygenases(COX)-2 and interleukin(IL)-$1{\beta}$ were slightly down-regulated by EA stimulation. The number of COX-2, IL-$1{\beta}$, tumor necrosis factor-${\alpha}$ immunoreactive cells were abundantly observed in paw edema. But these cells were decreased in nmber according to anti-edema effect of 15Hz EA. Conclusions: These results indicate that 15Hz EA stimulation have an alleviation action against carrageenan-induced edema and local inflammation.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.16-23
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• 2010

Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte differentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, $PPAR{\gamma}$ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) agonist, significantly reduced the levels of anti-adipogenic $PGE_2$ in IDX-conditioned hBM-MSC culture supernatants when compared to $PGE_2$ levels in the absence of $PPAR{\gamma}$ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease $PGE_2$ levels in culture. These results suggest that the role of $PPAR{\gamma}$ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic $PGE_2$ levels through the up-regulation of HPGD expression.

• BMB Reports
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• 제42권9호
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• pp.552-560
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• 2009

Cyclooxygenases (COX-1 and COX-2) are ER-resident proteins that catalyze the committed step in prostanoid synthesis. COX-1 is constitutively expressed in many mammalian cells, whereas COX-2 is usually expressed inducibly and transiently. Abnormal expression of COX-2 has been implicated in the pathogenesis of chronic inflammation and various cancers; therefore, it is subject to tight and complex regulation. Differences in regulation of the COX enzymes at the posttranscriptional and posttranslational levels also contribute significantly to their distinct patterns of expression. Rapid degradation of COX-2 mRNA has been attributed to AU-rich elements (AREs) at its 3’UTR. Recently, microRNAs that can selectively repress COX-2 protein synthesis have been identified. The mature forms of these COX proteins are very similar in structure except that COX-2 has a unique 19-amino acid (19-aa) segment located near the C-terminus. This C-terminal 19-aa cassette plays an important role in mediation of the entry of COX-2 into the ER-associated degradation (ERAD) system, which transports ER proteins to the cytoplasm for degradation by the 26S proteasome. A second pathway for COX-2 protein degradation is initiated after the enzyme undergoes suicide inactivation following cyclooxygenase catalysis. Here, we discuss these molecular determinants of COX-2 expression in detail.

• 대한화장품학회지
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• 제32권3호
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• pp.173-180
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• 2006

참깨(Sesamum indicum L.)는 1년생 초본식물로서 볶은 참깨나 참기름은 우리나라 식단에서 아주 중요한 조미용 양념 및 식용유지로서 이용되고 있다. 약효로는 동맥경화, 고혈압 및 노화 예방 등으로 알려져 왔으나, 참깨에 함유되어 있는 어떤 성분이, 이들 약효에 관여하고 있는지의 과학적인 규명이 미흡한 실정이다. 본 연구에서는 천연물 유래의 새로운 노화방지제를 개발하기 위해 참깨의 리그난 화합물(sesamin, sesamol, sesaminol, sesaminol diglucosides (SDG), sesaminol triglucosides (STG))의 항염증 활성을 검색하고, 그 중에서 항염증 효과가 가장 높게 나타난 sesamin을 전처치 방법과 동시처치 방법으로 NO 생성억제효과, 세포독성, inducible nitric oxide synthase (iNOS) 및 cyclooxygenases-2 (COX-2) 발현에 미치는 영향을 탐색하고 작용기작을 규명하고자 하였다. 리그난 화합물의 NO 생성억제효과를 탐색한 결과, sesamol, sesaminol, sesamin에서 NO 생성에 미치는 억제율이 높았으나, sesamol, sesaminol은 세포독성이 나타났다. 하지만 sesamin ($IC_{50}: 64{\mu}M$)은 세포독성은 없으면서 농도의존적으로 NO 생성을 억제시켰으며, iNOS 발현에서도 억제 효과를 보여주었다. 결론적으로 sesamin은 피부노화에 원인 중 하나이며 체내 염증반응의 중요 매개인자인 NO의 생성을 억제하는 항염증 물질로서 이와 같은 연구 결과는 향후 임상에서 항염증과 관련된 새로운 항노화 전략으로 개발하기 위해 기초자료로 응응될 수 있음을 시사한다.