• Journal of Nutrition and Health
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• v.23 no.3
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• pp.157-169
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• 1990

This study was designed to investigate the effect of supplementation of fish oil on serum apoprotein and platelet function in healthy young females. Eighteen female college students were divided into 3 groups. Each group fed a typical Korean diet supplemented with 15g, 12g, and 9g of fish oil respectively for 1-week. Blood samples were obtained 4 times, before supplementation, immediately after, 1-week after and 3-week after stopping supplementation. After 6-week break, the doses of fish oil were interchanged among 3 groups and the experiment was repeated to reduce interindividual variation. The concentration of apoprotein A, apoprotein B in the serum samples and the platelet adhesion, the platelet aggregation and bleeding time were determined immediately after supplementation of fish oil, 1-week after and 3-week after stopping supplementation and then the value compared with those of before supplementation period. The results obtained are summarized as follows: Serum apoprotein A levels decreased significantly(p<0.05), immediately after supplementation of fish oil in the 15g group. The serum apoprotein B levels did not show significant change. The platelet adhesion decreased significantly(p<0.05) 1-week after supplementation of fish oil in the 15g group. The platelet aggregation decreased significantly(p<0.01) immedeately after supplementation of fish oil in the 15g group.

• The Journal of Korean Medicine
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• v.30 no.6
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• pp.1-8
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• 2009

Objectives: Formulas for treatment of yin or yang deficiency conditions have been commonly used in traditional Korean medicine. The aim of this study is to examine the possible inhibitory effects of yin- or yang-tonifying formulas on in vivo anti-platelet activity and in vivo anti-thrombotic activity. Methods: We tested the effects of 26 types of yin- or yang-tonifying formulas on platelet aggregation induced by collagen in human whole blood using the impedance method of aggregometry and accessed a biomarker of platelet activation using thromboxane $B_2$ immunoassay. We also tested the anti-thrombotic effects of effective candidates on experimental models of thrombosis in mice. Results: 3 types of yin-tonifying formulas and 3 types of yin-yang-tonifying formulas were selected to be the most effective candidates (p<0.01). Also, through in vivo study, the antithrombotic activities of Igyeong-tang, Gamisipjeondaebo-tang, and Gamisoyo-san-treated groups, with recovery rate of 60, 50, and 45.45%, respectively, were observed to be higher than those of the control group (saline, 36.8%) in mouse acute thrombosis. Conclusion: These results show that yin-tonifying formulas are more effective in anti-platelet and anti-thrombotic activity than yang-tonifying formulas.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.173-195
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• 2022

Like vertebrates, insects synthesize various eicosanoids after the committed catalytic step of phospholipase A₂ (PLA₂). However, the subsequent biosynthetic steps exhibit some deviation from those of vertebrates. Due to little composition of arachidonic acid in insect phospholipids, PLA₂ releases linoleic acid, which is another polyunsaturated fatty acid and relatively rich in insect phospholipids, to synthesize arachidonic acid via chain extension and desaturation. Resulting arachidonic acid is then oxygenated into a prostaglandin (PG), PGH₂, by a specific peroxidase called peroxynectin, but not by cyclooxygenase. PGH₂ is then isomerized to various PGs such as PGA₂, PGD₂, PGE₂, PGI₂, and a thromboxane (TXB₂). All four epoxyeicosatrienoic acids such as 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET are also synthesized from arachidonic acid by oxygenation of vertebrate types of monooxygenases. However, the other type of eicosanoids called leukotrienes are found in insect tissues but their synthetic pathway is unclear. Eicosanoids mediate various insect physiological processes such as metabolism, excretion, immunity, and reproduction. Thus, identification of novel compounds interrupting eicosanoid biosynthesis would be a novel approach to develop insecticides. This review focuses on PGs and their immune mediation.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.375-383
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• 2006

The anti platelet effects of a novel guanidine derivative, KR-32570 ([5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine), were investigated with an emphasis on the mechanisms underlying its inhibition of collagen-induced platelet aggregation. KR-32570 significantly inhibited the aggregation of washed rabbit platelets induced by collagen $(10{\mu}g/mL)$, thrombin (0.05 U/mL), arachidonic acid $(100{\mu}M)$, a thromboxane (TX) $A_2$ mimetic agent U46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin $F_2,\;1{\mu}M$) and a $Ca^{2+}$ ATPase inhibitor thapsigargin $(0.5{\mu}M)$ ($IC_{50}$ values: $13.8{\pm}1.8,\;26.3{\pm}1.2,\;8.5{\pm}0.9,\;4.3{\pm}1.7\;and\;49.8{\pm}1.4{\mu}M$, respectively). KR-32570 inhibited the collagen-induced liberation of $[^3H]$arachidonic acid from the platelets in a concentration dependent manner with complete inhibition being observed at $50{\mu}M$. The $TXA_2$ synthase assay showed that KR-32570 also inhibited the conversion of the substrate $PGH_2$ to $TXB_2$ at all concentrations. Furthermore, KR-32570 significantly inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at $50{\mu}M$, which is the concentration that completely inhibits platelet aggregation. KR-32570 also decreased the level of collagen $(10{\mu}g/mL)$induced secretion of serotonin from the dense-granule contents of platelets, and inhibited the NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. These results suggest that the antiplatelet activity of KR-32570 against collagen-induced platelet aggregation is mediated mainly by inhibiting the release of arachidonic acid, $TXA_2$ synthase, the mobilization of cytosolic $Ca^{2+}$ and NHE-1.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.223-231
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• 2014

In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its $IC_{50}$ value was $175{\mu}g/ml$. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated $[CA^{2+}]_i$ mobilization and thromboxane $A_2$ ($TXA_2$) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated $[CA^{2+}]_i$ level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor ($IP_3R$) phosphorylation. These results suggest that the inhibition of $[CA^{2+}]_i$ mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of $IP_3R$. CE-WIB801C suppressed $TXA_2$ production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and $TXA_2$ synthase (TXAS). These results suggest that the inhibition of $TXA_2$ production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent $CA^{2+}$-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• Journal of the East Asian Society of Dietary Life
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• v.23 no.3
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• pp.311-319
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• 2013

The purpose of the present study is to investigate the effects of green tea catechin on microsomal phospholipase $A_2(PLA_2)$ activity and the arachidonic acid (AA) cascade in hearts of microwave exposed rats. Sprague-Dawley male rats weighing $100{\pm}10$ g were randomly assigned to one normal group and three microwave exposed groups. The microwave exposed groups were subdivided into three groups: catechin free diet (MW) group, 0.25% catechin (MW-0.25C group and 0.5% catechin (MW-0.5C) group according to the levels of dietary catechin supplementation. Rats were sacrificed $6^{th}$ day after microwave irradiations (2.45 GHz, 15 min). The heart microsome $PLA_2$ activity in the MW group was 130% greater than that of normal groups, whereas there was no significant difference between normal group and MW-0.25C, MW-0.5C group. The per- centage phosphatidyl ethanolamine (PE) hydrolyzed in the heart microsome in the MW was increased 54% by microwave irra- diation, whereas there was no significant difference between normal group and MW-0.5C group. The percentage phosphatidyl choline (PC) hydrolyzed in the heart microsome in the MW group was increased by 104% and by microwave irradiation, whereas there was no significant difference between normal group and MW-0.5C group. The formation of thromboxane $A_2(TXA_2)$ in the heart microsome was 70% greater in the MW group than in the normal group. However, the MW-0.25C and MW-0.5C group maintained the normal level. The formation of prostacyclin ($PGI_2$) in the heart microsome was 21% lower in the MW group than in the normal group, while that of MW-0.25C and MW-0.5C group were maintained in the normal group. The heart microsomal thiobarbituric acid reactive substances (TBARS) concentrations, as an index of lipid peroxide, were 71% greater in the MW group, as compared with normal group. However, the MW-0.25C and MW-0.5C group were 4.6% and 9.2% lower, respectively, than that of MW group. In conclusion, heart function appeared to be improved by green tea catechin supplementation due to its antithrombus action, which in return controls the AA cascade system.

• Journal of Rheumatic Diseases
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• v.24 no.4
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• pp.192-202
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• 2017

Objective. Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. Methods. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. Results. Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of $15-deoxy-^{{\Delta}12,14}$ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. Conclusion. Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.

• Journal of Ginseng Research
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• v.13 no.2
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• pp.202-210
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• 1989

The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.

• Journal of Nutrition and Health
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• v.37 no.7
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• pp.515-524
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• 2004

This study was performed to investigate effect of dried powders and ethanol extracts of garlic flesh and peel on lipid metabolism and antithrombogenic capacity in 16-month-old rats. Forty Sprague-Dawley male rats weighing 618.1$\pm$6.5 g were blocked into five groups according to body weight and raised for 3 months with control and experimental diets containing 5% (w/w) of dried powders of garlic flesh or peel, or ethanol extracts from equal amount of each dried powder and control diet. Plasma and liver total lipids, triglyceride and total cholesterol, and plasma HDL-cholesterol, throm-boxane $B_2$ (TX $B_2$), 6-keto-prostaglandin $F_{1a}$ (6-keto-PG $F_{1a}$) concentrations were measured. Total, insoluble and soluble dietary fibers contents were highest in peel powder followed by fresh powder, and those in ethanol extracts of flesh and peel, especially soluble, very low. Plasma and liver total lipids, triglyceride, and total cholesterol concentrations were lower in all the garlic experimental groups compared to Especially, flesh and peel powder lowered plasma total lipids, triglyceride and total cholesterol concentrations markedly, and flesh powder and flesh ethanol extract lowered liver total lipids, triglyceride and total cholesterol concentration remarkably. Plasma TX $B_2$ concentrations in garlic experimental groups were lower than that of control group, and 6-keto-PG $F_{1a}$ concentrations. In garlic experimental groups were higher than that of control group. Flesh ethanol extract group showed the lowest TX $B_2$ and the highest 6-keto-PG $F_{1a}$ concentrations among experimental groups, so TX $B_2$/6-keto-PG $F_{1a}$ ratio in flesh ethanol extract group was significantly lower than that of control group. Moreover, clotting time was significantly increased in flesh ethanol extract group as compared to control group. In conclusion, intakes of dried powders and ethanol extracts of garlic flesh and peel were effective in lowering lipid levels of liver and plasma. And also flesh ethanol extract diet was most effective in antithrombogenic activity among garlic experimental groups as TX $B_2$/6-keto-PG $F_{1a}$ ratio in flesh ethanol extract group was significantly lower and clotting time was significantly increased in this group as compared to control group.ntrol group.

• Journal of Ginseng Research
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• v.35 no.3
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• pp.325-330
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• 2011

Red ginseng saponin fraction-A (RGSF-A) contains a high percentage of panaxadiol saponins that were isolated from Korean red ginseng by ultrafiltration. The aim of this study was to elucidate the effects of RGSF-A on the porcine distal left anterior descending (LAD) coronary artery. The relaxant responses to RGSF-A were examined during contractions induced by 100 nM U46619 (9,11-dideoxy-9a,11a-methanoepoxy-prostaglandin F2a), a stable analogue of thromboxane A2. RGSF-A dose-dependently induced biphasic (fast- and slow-) relaxation in the distal LAD coronary artery in the presence of an intact endothelium. The fast-relaxation was quickly achieved in a minute, and then the slow-relaxation was slowly developed and sustained for more than thirty minutes after the administration of RGSF-A. The slow-relaxation had a tendency to be bigger than the fast-relaxation. Fast relaxation induced by RGSF-A was almost blocked by $N_{\omega}$-Nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase synthase inhibitor and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. However slow relaxation induced by RGSF-A was only partially inhibited by L-NAME and ODQ. In the endothelium-removed ring, RGSF-A evoked only slowrelaxation to a certain extent. These data suggest that RGSF-A induced both endothelium dependent fast- and slow-relaxation and endothelium independent slow-relaxation in the porcine distal LAD coronary artery. The endothelium dependent fast-relaxation is mediated by the nitric oxide (NO)-cGMP pathway, and the endothelium dependent slow-relaxation is at least partially mediated by the NO-cGMP pathway. However, the endothelium-independent slow-relaxation remains to be elucidated.