• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.193-199
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• 2014

The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin $D_2$ ($PGD_2$), leukotriene $C_4$ ($LTC_4$), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of $PGD_2$ and $LTC_4$ in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun $NH_2$-terminal kinase and p38), and the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

• Journal of Nutrition and Health
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• v.37 no.3
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• pp.182-192
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• 2004

Conjugated linoleic acid (CLA) is the mixture of positional and geometric isomers of linoleic acid (LA), which is found abundantly in dairy products and meats. This study was performed to investigate the anticarcinogenic effect of CLA in HepG2 hepatoma cells. HepG2 cell were treated with LA and CLA at the various concentrations of 10, 20, 40, 80 uM each at different incubation times. After each incubation times, cell proliferation, fatty acids incorporation into cell, peroxidation and postaglandin E$_2$ (PGE$_2$) and thromboxane $A_2$ (TXA$_2$) for the eicosanoid metabolism were measured. LA treated HepG2 cells were increased cell growth 6 - 70％ of control whereas CLA increased cell death the half of those in LA group (p 〈 0.001). LA and CLA were incorporated very well into the cellular membranes four times higher than in control according to concentration and longer incubation times. Moreover, LA synthesized significantly arachidonic acids corresponding with LA concentration compared to CLA supplementation. The supplementation with LA increased intracellular lipid peroxides concentration corresponding with LA concentration and five times higher than those in CLA significantly at any incubation times (p 〈 0.001). PGE$_2$ and TXA$_2$ levels were three to twenty times lower in condition of CLA treatments than LA, respectively. Overall, the dietary CLA might change the HepG2 cell growth by the changes of cell composition, production of lipid peroxide. Since CLA have not changed the levels of arachidonic acid of cell membrane, which was sources of eicosanoids, eicosanoid synthesis was not increased in CLA compared to LA. Our results was suggest CLA has a possibility to protect the progress of atherosclerosis because CLA does not produce lipid production and endothelial contraction factors in liver.

• Journal of Life Science
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• v.10 no.5
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• pp.529-532
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• 2000

Prostaglandin $E_2$(PG$E_2$) is an abundant eicosanoid in bone that has been implicated in a number of pathological states associated with bone loss, and is also known to stimulate matric metalloproteinase-1 systhesis and secretion in rat and human osteoblast cells, although the intracellular reaction remain unclear. Interleukin-1$\beta$ (IL-1$\beta$) is a cytokine that plays a critical role in bone remodelling and appears to act as a downstream effector of most bone-resorbing agents. However, it is still interesting to examine whether PG$E_2$ regulates IL-1$\beta$ expression by mouse osteoblasts or not. Here we demonstrate that PG$E_2$is a potent inducer of IL-1$\beta$ production by fetal osteoblasts.

• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.225-225
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• 2004

Acyl-CoA synthetase 4(ACS4) is an arachidonate-preferring enzyme aboundant in steroidogenic tissues and postulated to modulate eicosanoid production. Most of arachidonate present in cells is esterified predominantly in phospholipids. After its release by the action of calcium-dependent phospholipases, arachidonate can be converted to prostaglandins, thromboxanes, and leukotrenes via the cyclooxygenas and lipoxygenase pathways, respectively, depending on the cell type.(omitted)

• Korean Journal of Oriental Medicine
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• v.6 no.1
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• pp.81-87
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• 2000

Chungpesagan-Tang (CST), a Korean traditional prescription composed of oriental medical herbs, has been used successfully to improve human health and regimen. This study was designed to examine the inhibitory effects of CST against in vitro ischemia/reperfusion-induced inflammatory response. We have characterized the production of prostaglandin $E_2$ and arachidonic acid during ischemia/reperfusion in the human neuroblastoma SK-N-MC and human monocytic macrophage U937 cells and the inhibitory effect of CST on these inflammation-related substance formation has been found out in this study. This result suggested that CST used in this experiment reinforced antiinflammatory potentials and protected cells against ischemia/reperfusion-induced inflammatory resopnse.

• Proceedings of the Ginseng society Conference
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• 1993.09a
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• pp.28-29
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• 1993

From in vivo and in vitro experiments using Korean Red Ginseng and its main components. ginsenoside saponins, it was found that ginesenoside may exerts its anti-thrombotic action by decreasing $TXA_2$ formation in platelets and increasing $PGI_2$ formation in vascular walls. This may certainly contribute to prevention and development of atherosclerosis and thrombosis by administration of Korean Red Ginsengs.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.102.1-102.1
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• 2003

Phospholipase A$_2$(PLA$_2$) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid(AA), a precursor of eicosanoids including prostaglandins(PGs) and leukotrienes (LTs). The same reaction also produces lyso-phospholipids. So far, at least 19 enzymes that possess PLA2 activity have been identified, consists of low-molecular-weight, Ca$\^$2+/-requiring, secretory enzymes that have been implicated in a number of biological processes, such as modification of eicosanoid generation, inflammation, host defense, and atherosclerosis. (omitted)

• Journal of Nutrition and Health
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• v.38 no.10
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• pp.807-816
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• 2005

The objective of the study was to observe the effect of n-3 PUFA on cell proliferation and apoptosis by determining mRNA and protein of COX-2 and eicosanoid product and the mRNA and protein of Bu and Bcl-2 related to apoptosis in colon carcinogenesis of 1,2- dimethylhydrazine (DMH)-treated rats. Ninety male Sprague Dawley rats weighing about 170g were divided into 3 groups, control and n-3 PUFA supplemented groups (FO group: 6.2 mmoles n-3 PUFA; 2FO group: 12.4 mmoles n-3 PUFA) and fed experimental diet for 14 weeks. All rats were intramuscularly injected with DMH 15 mg/kg twice a week for 6 weeks to deliver total dose of 180 mg/kg body weight. Compared with the control group, 6.2 mmoles n-3 PUFA significantly reduced the levels of mRNA and protein expression of COX-2 and 2-series eicosanoids ($TXB_{2}$ and $PGE_{2}$) and decreased cell proliferation in colonic mucosa. However, high levels of n-3 PUFA supplementation significantly increased the levels of mRNA and protein expression of COX-2, TXB2 and PGE2. and increased cell proliferation which was similar level to that of control group. Compared with the control group, n-3 PUFA, regardless of the amount, significantly increased apoptotic index in colonic mucosa. Western blot and RT-PCR analyses showed that the levels of mRNA and protein expression of Bax were significantly increased by 6.2 mmoles n-3 PUFA, but decreased by 12.4 mmoles n-3 PUFA. The analyses also showed the levels of mRNA and protein expression of Bcl-2 were significantly reduced by 6.2 mmoles n-3 PUFA, but increased by 12.4 mmoles n-3 PUFA. The ratio of Bcl-2/Bax in mRNA and protein was significantly reduced by 6.2 mmoles n-3 PUFA but increased by 12.4 mmoles n-3 PUFA. Overall, these results indicate that n-3 PUFA could be effective in preventing colon carcinogenesis by reducing cell proliferation with lower level of COX-2 and 2-series eicosanoid, and increasing apoptosis by inducing pro-apoptotic gene, Bax and inhibiting anti-apoptotic gene, Bcl-2 in the colonic mucosa of DMH-treated rats. However, high level of n-3 PUFA supplementation could stimulate colon carcinogenesis by increasing cell proliferation and inhibiting apoptosis. (Korean J Nutrition 38(10): 807$\sim$816,2005)

• Korean journal of applied entomology
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• v.55 no.2
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• pp.129-138
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• 2016

Eicosanoids are a group of C20 oxygenated polyunsaturated fatty acids (PUFAs). To monitor biosynthetic precursors of these PUFAs, this study extracted fatty acids from different tissues of the beet armyworm, Spodoptera exigua, and assessed their compositions using GC/MS. Fifth instar larvae were dissected to isolate different tissues of gut, fat body, hemocytes, and integument. From each tissue, total lipids were extracted and fractionated into neutral lipid (NL), glycolipid (GL), and phospholipid (PL). Most tissues contained palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), and linolenic acid (18:3). However, their compositions were different among tissues and lipid types. Fat body and hemocytes possessed other type of fatty acids such as myristic acid (14:0) and three unknown fatty acids. Among lipid types, PL contained relatively high levels of linolenic acid than NL and GL, while it had lower saturated fatty acids. Total unsaturated fatty acid composition was varied among tissues and lipid types. PL was rich in unsaturated fatty acids in fat body, gut, and hemocytes. There was a significant influence of calcium-independent phospholipase $A_2$ ($iPLA_2$) on maintaining fatty acid composition because RNA interference of $iPLA_2$ expression significantly modified fatty acid compositions in NL and PL. However, this study did not detect arachidonic acid, a main eicosanoid biosynthesis precursor, in all tissues. This suggests an alternative biosynthesis of eicosanoids in insects, which is distinct from the biosynthetic pathway of mammals.