• Title/Summary/Keyword: Cyclooxygenases-2

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Palmitic acid inhibits inflammatory responses in lipopolysaccharide-stimulated mouse peritoneal macrophages

  • Lee, Ju-Young;Lee, Hye-Ja;Jeong, Ji-Ahn;Jung, Ji-Wook
    • Advances in Traditional Medicine
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    • v.10 no.1
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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.

Recent Advances in Anti-inflammatory Flavonoid Research since 2004

  • Kim Hyun-Pyo
    • Biomolecules & Therapeutics
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    • v.14 no.1
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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.

Screening of Arachidonic Acid Cascade Related Enzymes Inhibitors from Korean Indigenous Plants (2) (한국 자생식물로부터 아라키돈산 대사계 효소 저해제 검색 (2))

  • 정혜진;문태철;이은경;손건호;김현표;강삼식;배기환;안인파;권동렬
    • YAKHAK HOEJI
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    • v.47 no.2
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    • pp.69-77
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    • 2003
  • Arachidonic acid (AA), which is stored in membrane glycerophospholipids, is liberated by phospholipase $A_2$ (PLA$_2$) enzymes and is sequentially converted to cyclooxygenases (COXs) and lipoxygenases (LOXs) then to various bioactive PGs, and LTs. In order to find the specific inhibitors of AA metabolism especially PLA$_2$, COX-2, 5-LO and lyso PAF acetyltransferase, 120 Korean residential plants extracts were evaluated for their inhibitory activity on PGD$_2$, LTC$_4$ production from cytokine-induced mouse bone marrow-derived mast cells (BMMC) and arachidonic acid released from phospholipid and PAF production from lyso PAF. From this screening procedure, methanol extract of ten indigenous plant such as Salix gracilistyla, Sedum kamtschaticum, Cirsium chanroenicum, Hypericum ascyron, Astilbe chinensis, Agrimonia pilosa, Aristolochia manshuriensis, Vodia daniellii, Pyrola japonica, Styrax obassia were found to inhibit production of inflammatory mediators in vitro assay system.

Extracellular Prostaglandin $E_2$ Upregulation Effect of the Methanol Extract of Artemisia argyi

  • Lee, Kyoung In;Moon, Young Sook;Pyo, Byoung Sik;Choi, Chul Hee
    • Natural Product Sciences
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    • v.18 no.4
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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.

COX-2 increase tumor-associated angiogenesis and tumor growth by eNOS-dependent pathway (eNOS 의존적 pathway를 통한 COX-2의 tumor 성장 증가와 tumor 혈관신생 증가)

  • Sohn, Eun-Hwa;Nam, Seung-Koong
    • Proceedings of the KAIS Fall Conference
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    • 2011.05b
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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.

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Euphorbiae Humifusae Inhibits Egr-1, $NF{-\kappa}B$ and COX-2 Activity Stimulated by Phorbol 12-myristate-13-acetate (PMA에 의해 유도된 Egr-1, $NF{-\kappa}B$ 및 COX-2의 활성에 미치는 지금초 추출물의 영향)

  • Kim, Tae-Hwan;Jin, Cheng-Yun;Park, Sang-Eun;Kim, Won-Il;Park, Dong-Il;Kim, Gi-Young;Kim, Nam-Deuk;Hong, Sang-Hoon;Choi, Yung-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.2
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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.

THE DNA TOPOISMERASE I INHIBITOR $\beta$-LAPACHONE INHIBITS PROLIFERATION AND DOWNREGULATES CYCLOOXYGENASE-2 GENE EXPRESSION IN HUMAN PROSTATE CARCINOMA CELLS

  • Kong, Kyu-Ri;Park, Byung-Tae;Park, Yung-Hyun
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.95-95
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    • 2002
  • Cyclooxygenases (COXs) are key enzymes in the conversion of arachidonic acid into prostanoids, which are involved in cell proliferation and inflammation. Two distinct COXS have been identified: COX-l which is constitutively expressed and COX-2 which is induced by different products such as tumor promoters or growth factors.(omitted)

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Effects of Lignan Compound of Sesame on LPS-induced Nitric Oxide Generation in Murine Macrophage RAW 264.7 Cells (참깨의 리그난 화합물의 항염증 효과)

  • Lee, Hwa-Jeong;Son, Dong-Ju;Kang, Myung-Hwa;Lee, Bum-Chun;Hong, Jin-Tae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.3 s.58
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    • pp.173-180
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    • 2006
  • Sesame (Sesamum indicum L.), one of the oldest oilseed crops, has been known to posses antioxidative and inflammatory effects. This seed contains lignan compounds such as sesamin, sesamol, sesaminol, sesaminol diglucosides (SDG), and sesaminol triglucosides (STG). Sesamin, a major lignan in sesame, displayed several biological activities including a protective effects against oxidative damage in the skin. In the present study, we investigated the effect of sesamin, sesamol, sesaminol, SDG, and STG, on nitric oxide (NO) induction and inducible nitric oxide synthane (iNOS) and cyclooxygenases-2 (COX-2) expression in lipopolysaccharides (LPS)-treated RAW 264.7 cells. The results showed that sesamol and sesaminol significantly inhibited NO generation but they were also cytotoxicity however, sesamin effectively inhibited NO production ($IC_{50}: 64{\mu}M$) without my cytotoxic effect in LPS-stimulated macrophage RAW 264.7 cells. In further study, it was founded that sesamin inhibited the expression of inducible nitric oxide synthase but not COX-2 expression. These results suggest that sesamin may be useful for improvements of the inflammatory diseases.

Diphlorethohydroxycarmalol, Isolated from Ishige okamurae, Increases Prostaglandin E2 through the Expression of Cyclooxygenase-1 and -2 in HaCaT Human Keratinocytes

  • Kang, Gyeoung-Jin;Han, Sang-Chul;Koh, Young-Sang;Kang, Hee-Kyoung;Jeon, You-Jin;Yoo, Eun-Sook
    • Biomolecules & Therapeutics
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    • v.20 no.6
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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.