• Journal of Nutrition and Health
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• v.27 no.10
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• pp.967-978
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• 1994

This study was done to investigate the effect of age and dietary linolenic acid content and the linolenic acid/linoleic acid(LNA/LA) ratio on the lipid metabolism and formation of PGI2 and TXA2. The male Sprague-Dawley rats were fed 6 different with 0.2, 0.4, 0.6 of LNA/LA ratio within either 8% LNA(high LNA) or 4% LNA(low LNA) of fatty acid content for different feeding period(1, 4, 12 month). The dietary fat used were sesame oil, perilla oil, soybean oil and beef tallow. The concentration of serum total lipid, total cholesterol and HDL-C were increased with aging. Triglyceride concentration was decreased in 0.2 ratio of LNA/LA. The lipid content of liver showed similar tendency to that of serum. The ratio of PGI2/TXA2 was increased in 1 month rats and antithrombotic effect was reduced significantly with increasing age. The PGI2/TXA2 ratio was tended to be higher in diet of 0.2 and 0.4 LNA/LA ratio at high LNA level and in diet of 0.6 LNA/LA ratio at low LNA level. Especially PGI2/TXA2 ratio was increased linearly with rising LNA/LA ratio at low LNA level. It seemed that the LNA content and LNA/LA ratio had interaction to increase the antithrombotic effect bychanging TXA2 synthesis. And the dietary fatty acid related effect lowering the serum and liver lipid content, excepting triglyceride, was increased when dietary n3/n6 ratio was high(0.6) at both high and low n3 level. Therefore, it could not be recommended to consume large amount of n3 fatty acid or high ratio of n3/n6 to prevent cardiovascular diseases. These results suggested that the dietary fatty acid ratio of n3/n6 could be determined based on the n-3 content of dietary fat to reduce the risk of cardiovascular disease.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.227-233
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• 1999

The effects of 2-bromo-3-(3,5-tert-butyl-4-hydroxylphenyl)-1,4-naphthalenedione(TPN2), a synthetic vitamin K derivative, on platelet aggregation and its action mechanisms were investigated in rat platelet. TPN2 inhibited the platelet aggregation induced by collagen($10\mu\textrm{g}$/ml), thrombin(0.1 U/ml), A23187($10\mu\textrm{M}$) and arachidonic acid($100\mu\textrm{M}$) in concentration-dependent manner with $IC_{50}$ values of 6.5$\pm$1.3, 59.3$\pm$4.5, 13.0$\pm$2.37 and 2.9$\pm$$1.0\mu\textrm{M}$, respectively. Collagen-induced serotonin release was significantly reduced by TPN2. The elevation of intracellular free $Ca^{2+}$ concentration ([$Ca^{2+}$]i) by collagen stimulation was greatly decreased by the pretreatment of TPN2, which was due to the inhibition of calcium release from intracellular store and influx from outside of the cell. TPN2 also significantly reduced the thromboxane $A_2$($TXA_2$) formation in a concentration-dependent manner. The collagen-induced arachidonic acid (AA) release in [$^3H$]-AA incorporated platelet, an indicative of the phospholipase $A_2$ activity, was decreased by TPN2 pretreatment. TPN2 significantly inhibited the activity of thromboxane synthase, but did not affect the cyclooxygenase activity. From these results. it is suggested that TPN2 exert its antiplatelet activity through the inhibition of the intra-cellular $Ca^{2+}$ mobilization and the decrease of the $TXA_2$ synthesis.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.809-817
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• 1999

The effect of 2-(4-cyanophenyl)amino-1,4-naphthalenedione-3-pyridinium perchlorate (PQ5) on pla-telet aggregation and its action mechanisms were investigated with rat platelet. PQ5 inhibited the platelet aggregation induced by collagen ($6{\;}{\mu\textrm{g}}/ml$), thrombin (0.4 U/ml) and A23187 ($3{\mu}M$) in concentration-dependent manner with $IC_{50}$ values of 5.50, 25.89 and $37.12{\;}{\mu}M$, respectively. PQ5 also significantly reduced the thromboxane $A_2$ (TXA2) formation in a concentration dependent manner. The collagen-induced arachidonic acid (AA) release in [-3H]-AA incorporated platelet, an indication of the phospholipase $A_2$ activity, was decreased by PQ5 pretreatment PQ5 significantly inhibited the activity of thormboxane synthase only at high concentration ($100{\mu}M$), but did not affect the cyclooxygenase activity at all. Collagen-induced ATP release was significantly reduced by PQ5. Calcium-induced platelet aggregation experiment suggests that the elevation of intracellular free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) by collagen stimulation is decreased by the pretreatment of PQ5, which is due to the inhibition of calcium release from intracellular store and influx from outside of the cell. PQ5 did not showed the effect of anticoagulation as prothrombin time (PT) or activated partial thromboplastin time (APTT). Form these results, it is suggested that PQ5 exerts its antiplatelet activity through the inhibition of the intracellular $Ca^{2+}$ mobilization and the decrease of the $TXA_2$ synthesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1391-1398
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• 2005

The anti-thrombic properties of the oriental herbal medicine Daejowhan(DJW, 大造丸) which consists of 11 kinds of herbs (indicated as ratio) of Rehmanniae Radix 24%, Hominis Placenta 5%, Testudinis Carapax 9%, Eucommiae Cortex 9%, Asparagi Radix 9%, Phellodendri Cortex 9%, Achyranthis Radix 7%, Liriopis Tuber 7%, Angelicae Sinensis Radix 7%, Ginseng Radix 5% and Schizandrae Fructus 3% were investigated. The water extracts from DJW inhibited Platelet-activating factor(PAF) induced platelet aggregation. DJW was extracted with methanol and further fractionated by ethylacetate. A 70% methanol extract showed a strong inhibition against PAF-induced aggregation in vitro and in vivo assays. The ethylacetate soluble fraction was shown to have inhibitory effect on PAF-induced platelet aggregation in vitro assay. The ethylacetate soluble fraction specially protected against the lethality of PAF, while verapamil did not afford any protection. These results indicate that the water extracts and alcoholic-fractions inhibit the action of PAF in vivo by an antagonistic effect on PAF, so that it may be useful in treating disorders caused by PAF, such as acute allergy, inflammation, asthma, gastrointestinal ulceration, toxic shock and so forth. DJW was investigated regarding its assumed anti-thrombic action on human platelets which was deduced from its ability to suppress Arachidonic acid(AA)-induced aggregation, exocytosis of ATP, and inhibition of Cyclooxygenase(COX) and Thromboxane synthase(TXS) activity. The latter two effects were estimated from the generation of Prostaglandin $E_2(PGE_2)$ and Thromboxane $A_2(TXA_2)$ respectively. Exogenously applied AA ($100{\mu}mol/{\ell}$) provoked a $89\%$ aggregation of platelets, the release of 14 pmol ATP, and the formation of either 225 pg $TXA_2$ or 45 pg $PGE_2$, each parameter being related to 106 platelets. An application of DJW 5 min before AA dose-dependently diminished aggregation, ATP-release and the synthesis of $TXA_2$ and $PGE_2$ with $IC_{50}$ values of 74, 108, 65, $72{\mu}g/m{\ell}$, respectively. The similarity of the $IC_{50}$ values suggest an inhibition of COX by DJW as primary target, thus suppressing the generation of $TXA_2$ which induces aggregation of platelets and exocytosis of ATP by its binding on $TXA_2$-receptors.

• 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.

• The Korea Journal of Herbology
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• v.31 no.3
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• pp.13-22
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• 2016

Objectives： Arachidonic acid is control the thromboxane A2 (TXA2) and prostacycline (PGI2) synthesis, TXA2 increase lead to thrombus produced by induces platelet aggregation and vasoconstriction. Angelicae gigantis radix (RAR) is mainly used blood deficiency and stagnation. In previous studies, RAR has been reported that a vasodilating and blood clotting delay effects. In this study, investigate that anti-oxidant and anti-thrombotic effects of RAR by heat-process.Methods： The heated angelicae gigantis radix sample were made by 140, 180, and 220 ℃ and 4, 6, 9 and 12 min using water or 30% ethanol. The anti-oxidant effects were measured by total polyphenol, total flavonoid, DPPH and ABTS radical scavening activation. Anti-thrombotic effect conducted in samples that are determined to be effective through the anti-oxidant experiment such as angelicae gigantis radix roasted 180℃, and 220℃ and angelicae gigantis radix roasted with 30% ethanol 180℃, and 220℃.Results： Anti-oxidant parameters were efficacious in high temperature roasted AR. Also AR and EAR increased a inhibitory activity of FXa compared with RAR. The blood coagulation time of administration groups were significantly increased compare with control group. The TXB2 was significantly decreased in AR and EAR.Conclusions : We confirmed that whether AR and EAR administration has anti-oxidant and anti-thrombotic effect or not. As the results, AR and EAR were improved anti-oxidant effects and blood biochemistry compare with control group. This study provides scientific evidence that AR and EAR are have an anti-oxidant effect and anti-thrombotic effect, it expected that there is no difference between the two.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.418-427
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• 2003

Conjugated linoleic acid (CLA) is the mixture of positional and geometric isomers of linoleic acid (LA, C18:2 $\omega$6), which is found abundantly in dairy products and meats. This study was peformed to investigate the anticarcinogenic effect of CLA in MCF-7 breast cancer cells. MCF-7 cell were treated with LA and CLA at the various concentrations of 15, 30, 60, 120 UM each. After incubation for 48 and 72 hours, cell proliferation, fatty acids incorporation into cell, peroxidation and activities of antioxidant enzymes were measured. Postaglandin E$_2$ (PGE$_2$) and thromboxane $A_2$ (TXA$_2$) were measured for the eicosanoids metabolism. There was no cell growth differences in both of LA and CLA treated MCF-7 cells at 48 hr incubation. Compared to LA, cell growth was decreased by CLA treatment according to increasing concentration at longer incubation times, respectively (p<0.05). Both of LA and CLA was incorporated into the cellular lipids 22~54% higher than in control but LA incorporation was not so linear as CLA according to concentration. Arachidonic acid (C20:4, $\omega$6) was synthesized after treatment of LA but did not in CLA, respectively. The lipid peroxide concentration in LA 120 $\mu$M group increased as 1.7 times as that in CLA 120 $\mu$M treated. The activities of antioxidant enzymes such as glutathione peroxidase and glutathione reductase were increased by the supplementation with CLA 120 $\mu$M at 72 hr incubation (p<0.001) compared to LA, otherwise activity of superoxide dismutase was not different in both. PGE$_2$ and TXA$_2$ levels were lower in condition of CLA treatments according to lower levels of arachidonic acids than those in LA treated group, respectively. Overall, the dietary CLA might change the MCF-7 cell growth by the changes of cell composition, production of lipid peroxide, activities of antioxidant enzymes and eicosanoid synthesis compared to dietary LA.

• The Korean Journal of Pharmacology
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• v.20 no.1 s.34
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• pp.41-46
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• 1984

Cadmium (Cd) was administered by a series of weekly intraperitoneal injections at dose of 2mg/kg in rabbits and rats. The levels of malondialdehyde (MDA) and thromboxane $B^2(TXB_2)$ in platelet-rich plasma from Cd-poisoned animals were significantly higher than those of the control group. Furthermore, the inhibition of 6-keto-prostaglandin $F_{1{\alpha}}$, production in Cd-treated aorta ring was inversely related to the enhancement of platelet aggregation. These results suggest that Cd not only inhibits prostacyclin synthesis in the arterial endothelium, but also stimulates the platelet aggregation by enhancing thromboxane AZ production. These findings are assumed to support the evidence of an effect of Cd toxicity on the vascular wall and platelet function in raising arteriall pressure.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.221-232
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• 1988

Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled, streptozotocin (STZ)-induced diabetes is attributable to diabetes-associated, enhanced renal vasoconstrictor influence of endogenous thromboxane $(TX)A_2$. Rats which were injected with STZ after pretreatment with 3-O-methyl glucose (3OMG), an agent which prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (RBF; ml $min^{-1}$ $gKw^{-1}$; electromagnetic flow probe), systemic arterial pressure (BP; mm Hg) and renal vascular resistance (RVR;BP $RBF^{-1})$in pentobarbital-anesthetized rats during a control period were $5.9{\pm}0.3$(P<0.1_{VS}. CR), $115{\pm}3$ and $20.3{\pm}1.0$(P<0.1_{VS}. CR) for STZR (n=15), and $8.4{\pm}0.4$, $123{\pm}3$ and $15.1{\pm}0.8$ for age-matched control rats (CR; n= 15), respectively. Basal values of RBF, BP and RVR in 3OMG pretreated STZR were identical to CR. In preparations shown capable of renal vasodilatation, OKY 1581 (1 mg/kg, i.v. followed by 0.4 mg/kg min infusion) abolished arachidonate-induced $(TX)A_2$ synthesis, but did not alter basal BP, RBF or RVR in either STZR or CR (n=4/group). Similarly, i.r.a. infusion of SQ29548 (100 ng/ml RBF) abolished renal vasoconstriction induced by a TX/prostaglandin endoperoxide mimic, U46619, but had no discern able affect on RVR in either STZR (n=8) or CR (n=8). The data indicates that $TXA_2$ does not participate in the elevated basal RVR of STZR which are associated with the diabetic state.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.1
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• pp.161-174
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• 1997

Omega-3 fatty acids have been major research interests in medical and nutritional science relating to life sciences since after the epidemiologic data on Green3and Eskimos reported by several researchers clearly showed fewer per capita deaths from heart diseases and a lower incidence of adult diseases. Linolenic acid(LNA) is an essential fatty acid for human beings as well as linoleic acid(LA) due to the fact that vertebrates lack an enzyme required to incorporate a double bond beyond carbon 9 in the chain. In addition the ratio of omega-6 and 3 fatty acids seems to be important in terms of alleviation of heart diseases since LA and LNA competes for the metabolic pathways of eicosanoids synthesis. High consumption of omega-3 fatty acids in seafoods may control heart diseases by reducing blood cholesterol, triglyceride, VLDL, LDL and increasing HDL and by inhibiting plaque development through the formation of antiaggregatory substances like PGI$_2$, PGI$_3$ and TXA$_3$ metabolized from LNA. Omega 3 fatty acids also play an important role in neuronal developments and visual functioning, in turn influence learning behaviors. Current dietary sources of omega-3 fatty acids are limited mostly to seafoods, leafy vegetables, marine and some seed oils and the most appropriate way to provide omega-3 fatty acids is as a part of the normal dietary regimen. The efforts to enhance the intake of omega-3 fatty acids due to several beneficial effects have been made nowadays by way of food processing technology. Two different ways can be applied: one is add Purified and concentrated omega-3 fatty acids into foods and the other is to produce foods with high amounts of omega-3 fatty acids by raising animals with specially formulated feed best for the transfer of omega-3 fatty acids. Recently, items of manufactured and marketed omega-3 fatty acids fortified foodstuffs are pork, milk, cheese, egg, formula milk and ham. In domestic food market, many of them are distributed already, but problem is that nutritional informations on the amounts of omega-3 fatty acids are not presented on the labeling, which might cause distrust of consumers on those products, result in lower sales volumes. It would be very much wise if we consume natural products, result in lower sales volumes. It would be very much wise if we consume natural products high in omega-3 fatty acids to Promote health related to many types of adult diseases rather than processed foods fortified with omega-3 fatty acids.