• Natural Product Sciences
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• 제14권3호
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• pp.206-213
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• 2008

This study was designed to investigate the anti-inflammatory effects of mangiferin isolated from the rhizome of Anemarrhena asphodeloides, a natural polyphenol, on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Mangiferin dose-dependently inhibited LPS-induced nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ productions in RAW 264.7 macrophages and peritoneal macrophages isolated from C57BL/6 mice. Consistent with these data, mangiferin suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. In addition, the release of tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) and interleukin-6 (IL-6), and the mRNA expression levels of these cytokines were reduced by mangiferin in a dose-dependent manner. Moreover, mangiferin effectively inhibited the transcriptional activation of nuclear factor-kappa B $(NF-{\kappa}B)$. These results suggest that the anti-inflammatory properties of mangiferin are caused by iNOS, COX-2, $TNF-{\alpha}$, and IL-6 down-regulation due to $(NF-{\kappa}B)$ inhibition in RAW 264.7 macrophages.

• BMB Reports
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• 제48권2호
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• pp.109-114
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• 2015

The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

• Natural Product Sciences
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• 제10권6호
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• pp.344-346
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• 2004

Eight phenolic compounds (1-8) which were isolated from the barks of Ulmus macrocarpa were evaluated for their inhibitory activities on nitric oxide (NO) and prostagrandin $E_2$ (COX-2) production in $interferon-{\gamma}\;(INF-{\gamma})$ and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro. NO and COX-2 levels were moderately reduced by the addition of compounds (1-8). Among them 3,4,5,6,7 and 8 inhibited NO production in a dose dependent manner with an $IC_{50}$ of 92.2, 97.3, 36.1, 43.5, 32.8, 39.4 and 37.1 ${\mu}g/ml$, respectively (positive control, L-NMMA; 36.4 ${\mu}g/ml$), and 3,4,5,6,7 and 8 reduced the COX-2 level in a dose dependent manner with an $IC_{50}$ of 43.2, 24.8, 24.8, 33.4, 44.8 and 22.7 ${\mu}g/ml$, respectively (positive control, indomethacin; 23.4 ${\mu}g/ml$). These results suggest that the phenolic compounds may be developed as potential anti-inflammatory and cancer chemopreventive agents.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.73-77
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• 2000

Rheum undulatum L. has been used as Rhei Radix in Korean Pharmacopea although their pharmacological effects were not studied much. In this studym, we tested anti-inflammatory effect as a representative activity of Rheum undulatum L. extracts using cyclooxygenase (COX)-2 inhibition. Murine macrophage, Raw 264.7 cells were incubated with lipopolysaccharide (1 $\mu\textrm{g}$/ml) to induce COX-2. The prostagladin $E_2$ ($PGE_2$) levels as an indicator of COX-2 activity were determined in the culture medium using ELISA. Inhibition of acetylsalicylic acid (ASA) as a standard, aloe-emodin, chrysophanol, rhein, 80% ethanol extract of Rheum undulatum L. (Ex) and ether fraction (Fr) after acid hydrolysis of Rheum undulatum L. were tested in induced COX-2 described above. $IC_{50}$ values were 0.082 $\mu\textrm{g}$/ml for ASA. 181 $\mu\textrm{g}$/ml for aloe-emodin, 3.65 $\mu\textrm{g}$/ml for emodin, 144 $\mu\textrm{g}$/ml for chrysophanol, 39.8 $\mu\textrm{g}$/ml for rhein, 141 $\mu\textrm{g}$ of herb/ml for Ex, and 95.7 $\mu\textrm{g}$ of herb/ml for Fr. We found that Ex and Fr of Rheum undulatum L. were more effective than other anthraquinones, since their $IC_{50}$ are lower than others.

• Natural Product Sciences
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• 제22권1호
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• pp.53-59
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• 2016

Anti-inflammatory effects of dihydrobenzofuran neolignans isolated from Euonymus alatus leaves and twigs were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Six neolignans, (+)-simulanol (1), (+)-dehydrodiconiferyl alcohol (2), (-)-simulanol (3), (-)-dehydrodiconiferyl alcohol (4), (+)-dihydrodehyrodiconiferyl alcohol (5), threo-buddlenol B (6) effectively inhibited the production of nitric oxide (NO) induced by LPS, and the activity of iNOS. (-)-dehydrodiconiferyl alcohol (4), which showed the most potent inhibitory activity, attenuated the activity of iNOS enzyme and also the expression of iNOS and COX-2 proteins. The subsequent production of pro-inflammatory cytokines, interleukin-$1{\beta}$, interleukin-6, tumor necrosis factor-${\alpha}$ and prostaglandin E2 were also inhibited by the pretreatment of RAW264.7 cells with (-)-dehydrodiconiferyl alcohol (4). These neolignans are thought to contribute to anti-inflammatory effects of E. alatus, and expected to be potential candidates to prevent/treat inflammation-related diseases.

• Natural Product Sciences
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• 제24권4호
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• pp.247-252
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• 2018

Halophytes are expected to possess abundant secondary metabolites and various biological activities because of habitat in extreme environments. In this study, we collected 14 halophytes (Asparagus oligoclonos, Calystegia soldanella, Carex pumila, Chenopodium glaucum, Elymus mollis, Glehnia littoralis, Limonium tetragonum, Messerschmidia sibirica, Rosa rugosa, Salsola komarovii, Spergularia marina, Suaeda glauca, Suaeda maritima, and Vitex rotundifolia) native to Korea and compared their total polyphenol contents, antioxidant and anti-inflammatory activities. The total polyphenol contents of R. rugosa (27.28%) and L. tetragonum (13.17%) were significantly higher than those of the other 12 halophytes and L. tetragonum, R. rugosa, and M. sibirica showed significantly greater antioxidant activities than the other 11 halophytes, as determined by DPPH (2,2-diphenyl-1-picrylhydrazyl). A. oligoclonos, E. mollis, and C. pumila showed significantly greater anti-inflammatory activities than the other 11, as determined by NO (Nitric oxide) and $PGE_2$ (Prostaglandin $E_2$) levels. In contrast, these three extracts had normal and low total polyphenol contents among the 14 halophytes. Consequently, the total polyphenol content in the 14 studied halophytes appeared to be related to antioxidant, but not anti-inflammatory activity levels.

• 한국미생물·생명공학회지
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• 제49권4호
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• pp.528-533
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• 2021

The microalga, Tetrathelmis tetrathele, is used in the development of products for the aquaculture, food, and nutraceutical industries. In the present study, we investigated whether the T. tetrathele ethanolic extract (TTE), which has anti-inflammatory properties, can confer protection against alopecia and improve scalp health, influence the proliferation of human keratinocytes, HaCaT cells, and human hair follicle dermal papilla cells (HFDPC), or inhibit 5α-reductase activity. We found that TTE inhibited the production of the inflammatory mediator, nitric oxide (NO), and prostaglandin E₂ (PGE₂) without cytotoxicity in LPS-stimulated RAW 264.7 cells. In addition, TTE encouraged the proliferation of HaCaT cells and HFDPC. Our results showed that TTE had anti-inflammatory activities, proliferated HaCaT cells and HFDPC, and inhibited 5α-reductase activity. Therefore, we suggest that T. tetrathele could be a potent therapeutic agent for alopecia prevention and scalp improvement.

• Fisheries and Aquatic Sciences
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• 제25권6호
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• pp.311-319
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• 2022

Hyaluronic acid from Liparis tessellatus eggs (HALTE) was grafted with caffeic acid (CA-g-HALTE), ferulic acid (FA-g-HALTE), gallic acid (GA-g-HALTE), and nisin (Nisin-g-HALTE) and investigated for their anti-inflammatory and antioxidant potential in lipopolysaccharides-stimulated RAW 264.7 mouse macrophages. Nitric oxide (NO) generation and prostaglandin E₂ activity were measured after treatment with the grafted HALTE samples. All grafted HALTE samples exhibited more antioxidant activity against 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals than 2,2-diphenyl-1-picrylhydrazyl radicals. Nisin-g-HALTE showed the least antioxidant activity. Additionally, the NO assay results showed that all grafted samples had no cytotoxic effect on RAW 264.7 macrophages and reduced macrophage activity after treatment. The most effective concentrations of CA-g-HALTE and FA-g-HALTE were found to be above 100 ㎍/mL. Increased sample concentration resulted in increased activity except with Nisin-gHALTE at 100 ㎍/mL. CA-g-HALTE, FA-g-HALTE, GA-g-HALTE, and Nisin-g-HALTE were found to have antioxidant and anti-inflammatory potential, which can be further explored for use in food, cosmetic, nutraceutical, and biomedical applications.

• Molecules and Cells
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• 제26권5호
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• pp.486-489
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• 2008

Curcumin (diferuloylmethane), a pigment derived from turmeric, has anti-oxidant and anti-inflammatory activities. Accumulating evidence points to a biochemical link between increased oxidative stress and reduced bone density. Osteoclast formation was evaluated in co-cultures of bone marrow stromal cells (BMSC) and whole bone marrow cells (BMC). Expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) was analyzed at the mRNA and protein levels. Exposure to curcumin led to dose-dependent suppression of osteoclastogenesis in the co-culture system, and to reduced expression of RANKL in $IL-1{\alpha}$-stimulated BMSCs. Addition of RANKL abolished the inhibition of osteoclastogenesis by curcumin, whereas the addition of prostaglandin $E_2$ ($PGE_2$) did not. The decreased osteoclastogenesis induced by curcumin may reduce bone loss and be of potential benefit in preventing and/or attenuating osteoporosis.

• 대한의생명과학회지
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• 제15권2호
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• pp.141-146
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• 2009

Paclitaxel, an antimicrotubule agent, binds to beta-tubulin in the microtubule and stabilizes the polymer, thereby repressing dynamic instability. Here, we have demonstrated that microtubule cytoskeletal architecture involved in regulation of the COX-2 expression in chondrocyte treated with paclitaxel. Paclitaxel enhanced COX-2 expression and prostaglandin E2 production, as indicated by the Western blot analysis, reverse transcriptase PCR(RT-PCR) and immunofluorescence staining, and $PGE_2$ assay, respectively. In our previous data have shown that paclitaxel treatment stimulated activation of ERK-1/2 and p38 kinase(Im et al., 2009). SB203580, an inhibitor of p38 kinase, blocked the induction of COX-2 expression by paclitaxel. Also PD98059, an inhibitor of ERK-1/2 kinase was blocked the induced COX-2 expression. These results indicate that activation of ERK-1/2 and p38 kinase is required for COX-2 expression induced by paclitaxel in rabbit articular chondrocytes.