• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Journal of Acupuncture Research
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• v.20 no.3
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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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• v.18 no.1
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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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• v.42 no.9
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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.

• 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.