• YAKHAK HOEJI
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• v.56 no.6
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• pp.347-351
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• 2012

5-Lipoxygenase (5-LO) catalyzes the formation of two major groups of leukotrienes, LTB4 and cysteinyl leukotrienes (CysLT), and it has been implicated as a promising drug target to treat various inflammatory diseases. Since its role in mature osteoclasts (mOCs) had not been reported, we investigated the effect of 5-LO inhibitors on mOCs. We showed that 5-LO inhibitors dose-dependently decreases the number of mOCs. The effects of 5-LO inhibitors were reversible, suggesting that they did not cause any cellular damages in mOCs. We further demonstrated that the suppression of mOCs by 5-LO inhibitors was caused mainly by disruption of the actin ring formation. Similar effects were shown with CysLT receptor (CysLTR)1 antagonist in mOCs. The mRNA expression of CysLTR1 and the production of CysLT were increased in mOCs. These results indicate that CysLTR1 mediates the suppression of mOCs by 5-LO inhibitors. Taken together, this study demonstrated that 5-LO plays important role in mOCs and possibly a novel therapeutic target for bone resorption diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.241-249
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• 1998

Platelet-activating factor(PAF) enhanced interleukin-1(IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide(LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with $IC_{50}\;of\;2\;{\mu}M\;and\;5\;{\mu}M$, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at $1\;{\mu}M\;and\;5\;{\mu}M$, respectively. In addition, leukotriene $B_4$ and prostaglandin $E_2$ production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF- stimulated leukotriene $B_4$ and prostaglandin $E_2$ production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between $10^{-16}\;and\;10^{-8}$ M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.

• YAKHAK HOEJI
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• v.45 no.3
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• pp.287-292
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• 2001

To investigate whether phospholipase $A_2$pathway is involved in histamine release of rat peritoneal mast cells, we measured histamine release in the presence of various enzyme inhibitors involved in eicosanoid pathway, such as phospholipase $A_2$, cyclooxygenase and lipoxygenase. Phospholipase $A_2$inhibitors, manoalide and OPC, significantly inhibited histamine release induced by 100 $\mu$M ATP and 1$\mu$g/ml compound 48/80. Cyclooxygenase inhibitors, ibuprofen and indomethacin, significantly inhibited ATP-induced histamine release and lipoxygenase inhibitors, baicalein and caffeic acid, also significantly inhibited. To investigate the involvement of protein kinase in ATP- and compound 48/80-induced histamine release, we observed effects of protein kinase inhibitors on histamine release. Bisindolmaleimide (protein kinase C antagonist) dose-dependently inhibited both ATP and compound 48/80-induced histamine release. Tyrosine kinase inhibitors (methyl 2,5-dihydroxy cinnamate and genistein) dose-dependently inhibited ATP and compound 48/80-induced histamine release. Protein kinase C and tyrosine kinase seem to be involved in histamine release induced by ATP and compound 48/80. These results suggest that phospholipase $A_2$pathway as well as protein kinase C and tyrosine kinase are involved in histamine release of rat peritoneal mast cells by ATP and compound 48/80.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.3
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• pp.280-285
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• 1993

The bioactivity of garlic extract was evaluated, based on the inhibition of soybean lipoxygenase. While the inhibition of lipoxygenase by the chloroform extract (1$_{50}$ value after 10min precirculation, 55mg/$m\ell$) of garlic homogenate shows the property as irreversible inhibitors, the aqueous extract (1$_{50}$ value, 65mg/$m\ell$) appeared to contain mainly reversible inhibitors. In the related study, diallyldislufide and dimethyldisulfide inhibited the enzyme with 1$_{50}$ value of 1.3mM and 18mM, respectively. These disulfides demonstrated both irreversible and reversible patterns of inhibition. In addition, synthetic alliin(allylcysteine sulfoxide) was found to inhibit the enzyme at high concentration (approximately 22%, at 10mM), and its decomposition products showed the irreversible property in the inhibition, in contrast to S-ethyl cysteine sulfoxide which expressed no significant inhibition. Thus, it is suggested that the garlic macerate contains both irreversible and reversible sulfur inhibitors.itors.

• Korean Journal of Food Science and Technology
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• v.27 no.1
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• pp.19-24
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• 1995

The effect of several inhibitors such as ascorbic acid on the lipoxygenase in soybeans known to catalyze reaction resulting in racid off-flavors was examined in the soybean homogenates by the oxygen electrode method. Among 8 compounds added at homogenizing process, 10 mM ascorbic acid inhibited lipoxygenase-1 and lipoxygenase-2/3 activities to 41.7 and 49.8%, respectively. Inactivation of lipoxygenase-2/3 was highly accelerated by homogenization for 15 min at room temperature, so the activity was inhibited 70.8% comparing with the homogenization of 3 min. When soybean homogenates with 10 mM ascorbic acid was stored at $25^{\circ}C$ for 72 hrs, lipoxygenase-2/3 activities lowered to 52.8% whereas L-1 activities lowered to 15.8%. Since it is reported that lipoxygenase-2 is responsible for the off-flavor of soybean products, the inhibitory effect of ascorbic acid among several inhibitors investigated might be useful in soybean processing.

• Journal of Food Hygiene and Safety
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• v.8 no.3
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• pp.157-161
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• 1993

In order to get infonnations on the development of alcohol induced cardiovascular disorders, primary cultured vascular smooth muscle cells (PVSMC) were treated with acetaldehyde, one of the most reactive metabolites of ethanol. Acetaldehyde caused the striking release of lactate dehydrogenase (LDH) from PVSMC and it stimulated the prostaglandin synthesis in the same system. But it didn't induce cyclooxygenase activity. lipoxygenase inhibitors-propyl gallate and nordihydroguaiaretic acid could reverse the effect of acetaldehyde, but dexamethasone, a phospholipase $A_2\;(PIA_2)$ inhibitor and cyclooxygenase inhibitors except indomethacin could not protect the cells from acetaldehyde toxicity. These results indicate that enhanced prostaglandin synthesis by acetaldehyde is not a direct cause of cell death, but secondary effect due to the activation of PIAl and also, the roles of the lipoxygenase metabolites and/or $PIA_2$ activity itself might be more important in the cytotoxicity of acetaldehyde.

• Journal of Integrative Natural Science
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• v.4 no.2
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• pp.91-98
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• 2011

Quantitative structure-activity relationships (QSAR) have been applied for two decades in the development of relationships between physicochemical properties of chemical substances and their biological activities to obtain a reliable statistical model for prediction of the activities of new chemical entities. The fundamental principle underlying the QSAR is that the structural difference is responsible for the variations in biological activities of the compounds. In this work, we developed 3D-QSAR model for a series of 5-Lipoxygenase inhibitors, utilizing comparative molecular field analysis (CoMFA) and Topomer CoMFA methodologies. Our developed models addressed superiority of Topomer CoMFA over CoMFA. The CoMFA model was obtained with $q^2$=0.593, $r^2$=0.939, $Q^2$=0.334 with 6 optimum number of components (ONC). Higher statistical results were obtained with the Topomer CoMFA model ($q^2$=0.819, $r^2$=0.947, ONC=5). Further robustness of developed models was checked with the ANOVA test and it shows F=113 for CoMFA and F=162.4 for Topomer CoMFA model. Contour map analysis indicated that the more requirement of electrostatic parameter for improved potency.

• Bulletin of the Korean Chemical Society
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• v.32 no.10
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• pp.3752-3755
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• 2011

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.5
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• pp.313-320
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• 2012

In this study, we focused to identify whether eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone), an extract from Artemisia argyi folium, prevents $H_2O_2$-induced injury of cultured feline esophageal epithelial cells. Cell viability was measured by the conventional MTT reduction assay. Western blot analysis was performed to investigate the expression of 5-lipoxygenase by $H_2O_2$ treatment in the absence and presence of inhibitors. When cells were exposed to 600 ${\mu}M$ $H_2O_2$ for 24 hours, cell viability was decreased to 40%. However, when cells were pretreated with 25~150 ${\mu}M$ eupatilin for 12 hours, viability was significantly restored in a concentration-dependent manner. $H_2O_2$-treated cells were shown to express 5-lipoxygenase, whereas the cells pretreated with eupatilin exhibited reduction in the expression of 5-lipoxygenase. The $H_2O_2$-induced increase of 5-lipoxygenase expression was prevented by SB202190, SP600125, or NAC. We further demonstrated that the level of leukotriene $B_4$ ($LTB_4$) was also reduced by eupatilin, SB202190, SP600125, NAC, or nordihydroguaiaretic acid (a lipoxygenase inhibitor) pretreatment. $H_2O_2$ induced the activation of p38MAPK and JNK, this activation was inhibited by eupatilin. These results indicate that eupatilin may reduce $H_2O_2$-induced cytotoxicity, and 5-lipoxygenase expression and $LTB_4$ production by controlling the p38 MAPK and JNK signaling pathways through antioxidative action in feline esophageal epithelial cells.

• Journal of Korean Neurosurgical Society
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• v.29 no.1
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• pp.28-34
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• 2000

Object : To verify the effect of the lipoxygenase inhibitor and cycloxygenase inhibitor on meningioma cell proliferation. Method : Using two meningioma cell lines, cell proliferation was determined at 96 hrs after adding inhibitor (AA861, Nordihydroguaiaretic acid(NDGA), Indomethacin, acetyl-11-keto-beta-boswellic acid(AKBA) into medium by methyl tetrazolium salt/phenazine methosulfate(MTS/PMS) non-radioactive cell proliferation assay. We checked optical density with 490nm wavelength UV and this value was used as a proliferative index. The percent of inhibition was also calculated from this value. Conclusion : Indomethacin and NDGA showed no effect on meningioma proliferation. AA861 also showed no significant inhibitory effect, but AKBA demonstrated a significant inhibitory effect on meningioma cell proliferation.