• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.463-468
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• 2013

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated $K^+$ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane $A_2$ ($TXA_2$) and hypoxia-activated nonselective cation channel ($I_{NSC}$) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and $TXA_2$-activated $I_{NSC}$ was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased $I_{NSC}$ might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

• Journal of Nutrition and Health
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• v.33 no.6
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• pp.632-638
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• 2000

This study was designed to observe the effect of green tea on colon tumor incidence and biomarkers of colon carcinogenesis in 1, 2-dimethlhydrazine-treated rats. Male Sprague Dawley rats at 7 weeks of age were divided into two groups: control and green tea(GT) groups. Control rats had distilled water as drinking water but GT group received green tea extracts(2.5%, w/v water) as drinking water throughout the experiment periods. All rats were fed the experimental diet containing 15% fat by weight for 20 weeks. and were i.m. injected with DMH for 6 weeks to give total dose of 180mg/kg body weight. Tumor incidence was reduced in GT group (39%) compared with control group (56%) Green tea significantly reduced cell proliferation (total cells per crypt, crypt length and proliferative zone) in colonic mucosa and also significantly reduced the levels of preformed prostalandin E2(PGE2) and thromboxance B2(TXB2) in colonic mucosa but the fatty acid profile of total lipid in colonic mucosa was not significantly influenced by green tea. However the relative percent of C20:4 and the levels f preformed PGE2 and TXB2. were significantly higher in tumor tissue compared with normal surrounding mucosa.Green tea increased the fecal excretion of total bile acid but not scondary bile acid which is known as one of promoters for colon cancer,. These results suggest that green tea could have preventive effect against colon cancer when consumed daily by influencing on antioxidant effect and the metabolism of arachidonic acid.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.558-565
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• 2000

SK-1080 is one of the newly developed orally active nonpeptide angiotensinII $AT_1-receptor$ antagonist that selectively acts at $AT_1$ receptor with high affinity. The cardiac effect on ischemia/reperfusion injury of SK-1080 was compared with those of losartan, a prototype of this class, in isolated rat hearts. Isolated perfused rat heart was pretreated with drug for 10 min and then subjected to global ischemia for 30 min followed by reperfusion with- or without drug for 30 min. The possible additive effect of SK-1080 on the platelet aggregation and coagulation in human blood was also studied. We investigated whether SK-1080 effects the platelet aggregation induced by ADP, a platelet agonist partially dependent on $thromboxaneA_2$. The clotting times in the prothrombin time (PT) and activated partial thromboplastin time (APTT) were also examined in human plasma in vitro as coagulation screening test. SK-1080 improved reperfusion function (LVDP, left ventricular developed pressure; PRP, rate-pressure product) in a dose-dependent manner. SK-1080 reduced ADP-induced platelet aggregation compared with vehicle but less than losartan, and did not affect clotting times.

• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.94-94
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• 2001

Prostaglandin endoperoxide H synthase (PGHS) catalyzes the committed step in prostaglandins and thromboxane A$_2$-- oxygenation of arachidonic acid to the hydroperoxy endoperoxide PGG$_2$, followed by reduction PGG$_2$to the alcohol PGH$_2$. The two reactions by PGHS -- cyclooxygenase and peroxidase -- occur at distinct but structurally and functionally interconnected sites. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. Initially a peroxide reacts with the heme group, yielding Compound I and an alcohol derived from the oxidizing peroxide. Compound I next undergoes an intramolecular reduction by a single electron traveling from Tyr385 along the peptide chain to the proximal heme ligand, His388, and finally to the heme group. Following the binding of arachidonic acid, Tyr385 tyrosyl radical initiates the cyclooxygenase reaction by abstracting the 13-pro(5) hydrogen atom to give an arachidonyl radical, which sequentially reacts with two molecules of oxygen to yield PGG$_2$. In order to characterize PGHS peroxidase active site, we examined various lipid peroxides with purified recombinant ovine PGHS proteins and determined the rate constants. The results have shown that twenty-carbon unsaturated fatty acid hydroperoxides have similar efficiency in peroxidation by PGHS, irrespective of either the location of hydroperoxy group or the number of double bonds. It was also confirmed by the subsequent study with PGHS peroxidase active site mutants.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.218-223
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• 2011

In this study, we investigated the effect of spinach saponin-enriched fraction (SSEF) on collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation. SSEF inhibited collagen-induced platelet aggregation, and which was involved in the inhibition of thromboxane $A_2$ ($TXA_2$) production, an intracellular $Ca^{2+}$-agonist as an aggregation-inducing autacoidal molecule. In addition, SSEF significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonists as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that SSEF might inhibit $Ca^{2+}$-elevation and $TXA_2$ formation by increasing the production of $Ca^{2+}$-antagonistic molecules cAMP and cGMP. These mean that SSEF is a potent inhibitor of collagen-stimulated platelet aggregation. On the other hand, prothrombin time (PT) and activated partial thromboplastin time (APTT) were potently prolonged by SSEF. These findings suggest that SSEF prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that SSEF may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

• 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.

• Journal of Nutrition and Health
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• v.35 no.5
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• pp.505-511
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• 2002

The study was designed to compare the anti-carcinogenic effect of different level of conjugated linoleic acid (CLA) in 1,2-dimethylhydrazine (DMH)-treated rats by determining biomarkers (apoptosis, cell proliferation, eicosanoids, 1,2-diacylglycerol) and phospholipid fatty acid profile in colonic mucosa. Eighty male Sprague Dawley rats weighing 180-220g were randomly divided into 4 groups depending on the content of CLA, i.e. 0.0% CLA, 0.5% CLA, 1.0% CLA, 1.5% CLA. The experimental diet contained protein 21.6%, carbohydrate 54.6%, and fat 14.5% including CLA mixture at different level by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total amount of 180 mg/kg body weight. Regardless of the amount of CLA supplemented to diet, CLA significantly increased the apoptotic index but did not have significant effect on cell proliferation in colonic mucosa. CLA was undetected in colonic mucosal phospholipid of rats fed the 0% CLA diet and increased to 5.9mg/g phospholipid in rats fed the 0.5% diet. The apoptotic index was increased by 251% and the 1,2-DAG content was decreased by 57% in rats fed 0.5% CLA. No further changes in these variables were observed when CLA in the diet was raised to 1.0% or 1.5%. However, dietary CLA decreased mucosal levels of prostaglandin (PG)E$_2$, thromboxane (TX)B$_2$, and arachidonic acid in dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanism probably involving increased apoptosis.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.164-179
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• 2002

Object: Death rate due to hypertension, atherosclerosis, ischemic heart disease and cerebral infarction induced by Westernized diet and increased average life span is on the rise. Decrease in blood circulation, activation of thrombus generation and intravascular lipid accumulation, cited as the principal causes of the above mentioned diseases in recent studies, result in circulatory disturbance and blood vessel obstruction leading to ischemic cell death of heart, brain and peripheral vessels. Method: We investigated the biochemical changes in microvascular permeability, aggregation of platelet and the intravascular lipid accumulation in induced-diabetic rat using Streptozotocin. We also studied the effects of Woohwangcheongsirn-won after oral administration on blood circulation, platelet function and lipid metabolism. The results are as follows: I. Woohwangcheongsim-won increased blood circulation in microvessels. 2. Woohwangcheongsim-won increased the reduced erythrocyte deformability in diabetes. 3. Woohwangcheongsim-won induced the reduction of contents of 2, 3-DPG, but failed to affect the reduced contents of ATP in erythrocyte in diabetes. 4. Woohwangcheongsim-won reduced the activity of Ca/sup 2+/-ATPase in the membrane of erythrocyte. 5. Woohwangcheongsim-won reduced the platelet aggregation evoked by platelet agglutinin factor. 6. Woohwangcheongsim-won reduced the production of platelet-derived granules. 7. Woohwangcheongsim-won reduced the production of metabolites of arachidonic acid in diabetes, and also reduced the production of increased thromboxane B2. 8. Woohwangcheongsim-won reduced the synthesis of oxidized LDL-cholesterol. In conclusion, Woohwangcheongsim-won enhanced blood circulation in microvesseles, erythrocyte deformability and inhibited the increased platelet aggregation and the synthesis of oxidized LDL-cholesterol in diabetes. Therefore Woohwangcheongsim-won is believed to positively affect blood circulation (J Korean Oriental Med 2002;23(2):164-179)

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.525-530
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• 2000

During reperfusion of skeletal muscle after ischemia, lipid mediators, mainly eicosanoids, are released and may have a role in the pathogenesis of reperfusion injury. To validate the role of eicosanoids in the ischemia-reperfusion induced functional deficits in skeletal muscle, we compared muscle edema and the changes of eicosanoid concentration in the rat hind limb after ischemia-reperfusion injury by application of tourniquet. After 4 hours of ischemia, reperfusion was established for 4 hours by releasing tourniquet. To assess tissue damage, edema, and wet/dry weight ratios were determined and the eicosanoid concnentrations were measured by the HPLC. The muscle edema and the release of cyclooxygenase metabolites were not induced by the ischemia itself rather they were significantly increased by reperfusion. Indomethacin treatment ameliorated limb edema and decreased the release of $6-keto-PGF_{1{\alpha}},$ thromboxane $B_2,$ and $PGE_2$ inducedby reperfusion. But the inhibitory effect of indomethacin on edema (35%) was relatively low than the inhibitory effect on release of cyclooxygenase metabolites (up to 69%) by reperfusion. These results support the view that cyclooxygenase products may play a significant role in the formation of muscle injury by ischemia-reperfusion and suggest that nonsteroidal antiinflammatory agents might be partially beneficial to the management of acute limb ischemia-reperfusion injury.