• Title/Summary/Keyword: 5(S)-HETE

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Inhibition of Red Ginseng on 5-Hydroxyeicosatetraenoic Acid (5-HETE) Biosynthesis from Arachidonic Acid in Helicobacter Pylori-infected Gastric Cells

  • Park Soo-Jin
    • Nutritional Sciences
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    • v.9 no.3
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    • pp.152-158
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    • 2006
  • Helicobacter pylori (H. pylori) infection rapidly stimulated either COX-2 or 5-LOX and released arachidonic acid metabolites that have been considered as pivotal mediators in H. pylori-induced inflammatory responses. To determine whether red ginseng extract (RGE) can suppress the biosynthesis of 5(S)-hydroxyeicosatetraenoic acids (HETE), a precursor metabolite of leukotrienes B4 (LTB4) in H. pylori-provoked inflammatory responses in gastric epithelial cells, the biosynthesis of monohydroxy fatty acids was measured using radioactive arachidonic acid and validated by RP-HPLC using non-radioactive AA as substrate in AGS cells cocultured with H. pylori (ATCC 43504) with or without pretreatment of RGE. Among three known major HETEs, H. pylori infection specifically induced the biosynthesis of $^{14}C-5(S)-HETE$ rather than the complex of $^{14}C-15S-/^{14}C-12(S)-HETE$ from $^{14}C-AA$, concomitantly obtained by HPLC(p<0.01). RGE, 1 to $100{\mu}g/ml$, selectively suppressed H. pylori-stimulated $^{14}C-5(S)-HETE$ production implying the attenuation of 5-lipoxygenase activity, of which was similar to known LOX inhibitor NDGA $(10{\mu}M)$ (p<0.01). However, the amount of 5(S)-HETE was significantly reduced by higher dose of RGE $(100{\mu}g/ml)$ (p<0.05). These results indicated that LOX pathway might be one of principle pathogenic mechanisms of H. pylori and red ginseng could be a nutraceutical against H. pylori infection through inhibiting action of LOX activity.

Antioxidant Effect of Green Tea Extracts on Enzymatic Activities of Hairless Mice Skin Induced by Ultraviolet B Light (녹차추출물에 의한 쥐표피의 효소에 대한 항산화 효과)

  • Ryu, Beung-Ho;Park, Chun-Ok
    • Korean Journal of Food Science and Technology
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    • v.29 no.2
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    • pp.355-361
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    • 1997
  • This study was carried out to investigate the acute cutaneous enzymatic antioxidant activity of green tea extracts (GTE) on hairless mice skin after a signal exposure to ultraviolet B radiation. GTE has been in corporated at concentration of 5, 25, 50 and $100\;{\mu}g$ into hairless mice skin. Under exposure conditions of $1.0\;joule/cm^{2}$, impairment of cutaneous enzymatic activity was observed. Catalase and glutathione reductase were significantly influenced in dose-dependent manner by GTE, however glutathione peroxidase and superoxide dismutase were not affected. To measure inhibition effect of the GTE on lipoxygenase. $50\;{\mu}g$ GTE extract was added in vitro to arachidonis acid. GTE showed higher inhibition effect on 5-hydroxyeicosatetraenoic acid (HETE) and 8-HETE than metalolic products of 12- or 15-HETE. The addition of 5, 25, 50 and $100\;{\mu}g$ GTE inhibited the metabolite formation of 5-HETE by 32, 52, 62 and 80%, respectively, and the metabolite formation of 8-HETE by 36, 47, 70 and 84%, respectively.

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Contributory Role of BLT2 in the Production of Proinflammatory Cytokines in Cecal Ligation and Puncture-Induced Sepsis

  • Park, Donghwan;Ro, MyungJa;Lee, A-Jin;Kwak, Dong-Wook;Chung, Yunro;Kim, Jae-Hong
    • Molecules and Cells
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    • v.44 no.12
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    • pp.893-899
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    • 2021
  • BLT2 is a low-affinity receptor for leukotriene B4, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB4 [leukotriene B4] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB4 and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

Leukotriene B4 receptors contribute to house dust mite-induced eosinophilic airway inflammation via TH2 cytokine production

  • Park, Donghwan;Kwak, Dong-Wook;Kim, Jae-Hong
    • BMB Reports
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    • v.54 no.3
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    • pp.182-187
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    • 2021
  • Leukotriene B4 (LTB4) is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4, BLT1, and BLT2 play mediatory roles in the allergic airway inflammation induced by ovalbumin (OVA). However, considering that house dust mites (HDMs) are the most prevalent allergen and well-known risk factor for asthmatic allergies, we are interested in elucidating the contributory roles of BLT1/2 in HDM-induced allergic airway inflammation. Our aim in this study was to investigate whether BLT1/2 play any roles in HDM-induced allergic airway inflammation. In this study, we observed that the levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid)] were significantly increased in bronchoalveolar lavage fluid (BALF) after HDM challenge. Blockade of BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or 12-lipoxygenase (12-LO) markedly suppressed the production of TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lung inflammation and mucus secretion in an HDM-induced eosinophilic airway-inflammation mouse model. Together, these results indicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDM-induced airway inflammation by mediating the production of TH2 cytokines. Our findings suggest that BLT1/2 may be a potential therapeutic target for patients with HDM-induced allergic asthma.

Anti-inflammatory action of ethanolic extract of Ramulus mori on the BLT2-linked cascade

  • Park, Geun-Soo;Kim, Jeong-Keun;Kim, Jae-Hong
    • BMB Reports
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    • v.49 no.4
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    • pp.232-237
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    • 2016
  • Mulberry tree twigs (Ramulus mori) contain large amounts of oxyresveratrols and have traditionally been used as herbal medicines because of their anti-inflammatory properties. However, the signaling mechanism by which R. mori exerts its anti-inflammatory action remains to be elucidated. In this study, we observed that R. mori ethanol extracts (RME) exerted an inhibitory effect on the lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokine interleukin-6 (IL-6) in Raw264.7 macrophage cells. Additionally, RME inhibited IL-6 production by blocking the leukotriene B4 receptor-2 (BLT2)-dependent-NADPH oxidase 1 (NOX1)-reactive oxygen species (ROS) cascade, leading to anti-inflammatory activity. Finally, RME suppressed the production of the BLT2 ligands LTB4 and 12(S)-HETE by inhibiting the p38 kinase-cytosolic phospholipase A2-5-/12-lipoxygenase cascade in LPS-stimulated Raw264.7 cells. Overall, our results suggest that RME inhibits the 'BLT2 ligand-BLT2'-linked autocrine inflammatory axis, and that this BLT2-linked cascade is one of the targets of the anti-inflammatory action of R. mori.

Antioxidant Constituents from Melothria heterophylla; Regulation of Matrix Metalloproteinase-1 Expression in Ultraviolet A-irradiated Human Dermal Fibroblasts (백렴으로부터 항산화 물질의 분리와 자외선이 조사된 사람 섬유아세포의 Matrix Metalloproteinase-1 발현에 미치는 영향)

  • Cho, Young-Ho;Kim, Jin-Hui;Sim, Gwan-Sub;Lee, Bum-Chun;Pyo, Hyeong-Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.4 s.54
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    • pp.323-327
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    • 2005
  • Although many studies have been performed to elucidate the molecular consequence of ultraviolet irradiation on an aging, little is known about the effect of natural products. Matrix metalloproteinases (MMPs) we known to play an important role in (a) photoaging. Hete we investigated the effect of $1,2,4,6-tetra-O-galloyl-{\beta}-{_D}-gluco- pyranose (1)$ and 3,4,5-trihydroxybenzoic acid (2) on the expression of MMP-1 in UVA-irradiated human skin fibroblasts (products), (on the) activity of MMP-1, and (on the) scavenging activities of free radicals. Compounds 1 and 2 were isolated from Melothria heterophylla (Cucurbitaceae). These compounds were found to scavenge free radicals and reactive oxygen species (ROS) and were measured to have the $SC_{50}$ values of $3.9{\mu}M\;and\;13.3{\mu}M$ against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and $4.3{\mu}M\;and\; 4.0{\mu}M$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Compounds 1 and 2 showed a dose-dependent inhibitory effect on the e):pression and activity of MMP-1 in the UVA-irradiated human skin fibroblasts. Therefore, we concluded that compounds 1 and 2 significantly inhibited MMP-1 expression at the protein level. Also, these compounds were determined to have a potent antioxidant activity. From these results, we suggest that these compounds nay be used as (a) new anti-aging agents for the photo-damaged skin.