• Journal of Chest Surgery
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• v.28 no.12
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• pp.1079-1095
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• 1995

Recently endogenous digitalis-like substances were found in the blood of various cardiovascular diseases and they have been considered one of the causes of evoking hypertension. However, the mechanism of endogenous digitalis-like substances-induced hypertension is not clarified yet. Therefore, the effects of Na-K pump inhibition on the contractility of vascular smooth muscle[conduit and resistant artery were investigated, using organ bath and bioassay experiment. Aortic and carotid arterial rings[conduit artery and the branches of brachial and superior mesenteric artery[resistant artery were used to find the effect of Na-K pump inhibition. The results obtained were as followes;The magnitudes of contractions induced by norepinephrine, serotonin, or acetylcholine in all these arteries were significantly increased by the inhibition of Na-K pump. The increased contractile responses to these agonists, especially to serotonin, were much more prominant in resistant arteries. Nitroprusside-induced relaxations were attenuated by Na-K pump inhibition and there were no significant differences in the effects of Na-K pump inhibition on nitroprusside-induced relaxations of these blood vessels. Endothelium-dependent relaxation was suppressed by the inhibition of Na-K pump, especially by the administration of ouabain, and this inhibitory effect was much more prominent in the branches of superior mesenteric artery, compared with other arteries. In the branches of superior mesenteric arteries, endothelium-dependent relaxation was completely blocked by ouabain. The release of EDRF was partially suppressed by Na-K pump inhibition.From the above results, it is suggested that the hypertension due to the increase in vascular resistance can be evoked by the inhibition of Na-K pump and endogenous digitalis-like substances induce hypertension through this mechanism.

• Journal of Ginseng Research
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• v.3 no.1
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• pp.66-93
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• 1979

Panax ginseng C. A. Meyer, which has been known for more than EWO years. occupies a Particular prince in folk medicine as so called tonic remedy. The pharmacolgical investigations of ginseng, based on the scientific concepts and methodology, have been performed by many researchers through the past 50∼60 years at different parts of the world. The pharmacological action of Panax ginseng compiled from the numerous reports can be summarized as follows: 1. On central nervous system, the effect of Panax ginseng is timulatory in smaller doses and somewhat depressive in larger doses. From the psychopharmacological aspect, ginseng seems to increase the mental efficiency of man. 2. Ginseng has the effect tending to Protect organism from various physical and chemical stresses. 3. The growth and basal metabolic rates of experimental animals are stimulated by ginseng. Ginseng also prolongs the survival time of animals under adverse influences. 4. Increasing the physical and mental efficiency, ginseng postpones the onset of fatigue and increases the working capacities. 5. In the case of the intravenous administration of ginseng, a transitory and slight hypotensive effect is observed. These hypotensive effects seems to include that of a direct action and actions related to the release of histamine and/or serotonin by ginseng. 6. It is Presumed that ginseng lowers the elevated bleed ingar and cholesterol level. 7. Ginseng tends to increase the gastrointestinal motizity and tone 8. It is presumed that ginseng Promotes the iron metabolism and activates the hematopoietic factors. 9. Ginseng tends to stimulate the biosynthesis of nucleic acid and release of histamine and serotonin. 10. The toxicity end adverse reactions of ginseng appear to be nothing that warrants apprehension. 11. Anticancer erects of ginseng seem to be due to indirect action rather than direct action on cancer cell, by improving the host condition 12. Recent clinical trials of ginseng harts obtained sent good results, but Present trial is still limited in its range, so it is necessary to broaden the scope of trial covering many kinds of organs and diseases. From the above, although it appears that substantial advancements have been achieved in the studies on the Pharmacological actions of Panax ginseng there are many discrepancies noticed in the reported data. Furthermore the precise mechanisms of actions of ginseng are sometimes obscure, even unknown in other actions as the students stand now. The main reasons for this are considered to be that even though saponin has been identified at one of the active substances of ginseng, other components have not fully been identified and that the experimental approaches of the investigations varied with different researchers. Thus a thorough analysis of the chemical components and newer standardized concepts and metohds appear to be the pre-requisites for further study of the pharmacolgical effects and mechaisms of Panax ginseng.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.1-9
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• 1992

Catecholamines, serotonin and their metabolites were measured in the posterior hypothalamus of urethane-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) using brain microdialysis which is a recently developed experimental method to measure the release of neurotransmitters and their metabolites at the localized brain area in vivo. Microdialysis probe was implanted stereotaxically to the rat posterior hypothalamus and perfused by Ringer's solution. Monoamines and their metabolites were quantified by reverse phase high performance liquid chromatography with electrochemical detection. In vitro recovery test of microdialysis showed that there exist inverse relationship between the perfusion flow rate and the relative recovery of neurochemical compounds. The estimated extracellular concentration of dopamine was about 32 nM, of norepinephrine 50 nM, of epinephrine 50 nM, of serotonin 73 nM, of 3, 4-dihydroxyphenylacetic acid (DOPAC) 281 nM, of homovanillic acid (HVA) 181 nM, and of 5-hydroxyindoleacetic acid (5HIAA) 3767 nM in the hypothalamic perfusate of the normotensive rat. There was no difference in the basal level of monoamines between the SHR and the WKY. In contrast, the level of DOPAC, HVA and 5HIAA in SHR was higher than that in the WKY, This study demonstrated that the microdialysis technique should be an applicable tool for in vivo measurement of central neurochemical substances.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.638-644
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• 2023

Background: The anti-platelet activity of the saponin fraction of Korean Red Ginseng has been widely studied. The saponin fraction consists of the panaxadiol fraction (PDF) and panaxatriol fraction (PTF); however, their anti-platelet activity is yet to be compared. Our study aimed to investigate the potency of anti-platelet activity of PDF and PTF and to elucidate how well they retain their anti-platelet activity via different administration routes. Methods: For ex vivo studies, Sprague-Dawley rats were orally administered 250 mg/kg PDF and PTF for 7 consecutive days before blood collection via cardiac puncture. Platelet aggregation was conducted after isolation of the washed platelets. For in vitro studies, washed platelets were obtained from Sprague-Dawley rats. Collagen and adenosine diphosphate (ADP) were used to induce platelet aggregation. Collagen was used as an agonist for assaying adenosine triphosphate release, thromboxane B2, serotonin, cyclic adenosine monophosphate, and cyclic guanosine monophosphate (cGMP) release. Results: When treated ex vivo, PDF not only inhibited ADP and collagen-induced platelet aggregation, but also upregulated cGMP levels and reduced platelet adhesion to fibronectin. Furthermore, it also inhibited Akt phosphorylation induced by collagen treatment. Panaxadiol fraction did not exert any antiplatelet activity in vitro, whereas PTF exhibited potent anti-platelet activity, inhibiting ADP, collagen, and thrombin-induced platelet aggregation, but significantly elevated levels of cGMP. Conclusion: Our study showed that in vitro and ex vivo PDF and PTF treatments exhibited different potency levels, indicating possible metabolic conversions of ginsenosides, which altered the content of ginsenosides capable of preventing platelet aggregation.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.33-38
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• 2010

Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The oral administration of sibutramine is followed by its dose-related side effects. In this study, sibutramine was formulated into drug in adhesive (DIA) patches in an attempt to overcome these problems. The effects of different formulation variables including pressure-sensitive adhesive (PSA), loading amount of drug, thickness of matrix and enhancer on the skin permeation of the drug were evaluated using excised hairless mouse skin. In the acrylic adhesive with carboxyl functional group, low release of sibutramine was observed due to the strong interaction between carboxyl group of adhesive and amine group of sibutramine. The acrylic adhesive without functional group provided good adhesion force and allowed high drug loading. Changing drug load as well as thickness of the matrix was found to alter permeation rate. $Crovol^{(R)}$ PK40 and $Crovol^{(R)}$ A40, were found to be effective enhancers for sibutramine. The optimized patch contained 20% sibutramine, and 5% $Crovol^{(R)}$ A40 as permeation enhancer, in $80\;{\mu}m$ thick Duro-$Tak^{(R)}$ 87-9301 matrix.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.149-154
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• 1994

Anti-allergic and anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were evaluated in mice and rats. Several criteria were employed to assess the anti-allergic and anti-inflammatory actions of Cimicifuga heracleifolia, such as hyaluronidase activity, mediators-induced vascular permeability changes, 48 hour homologous passive cutaneous anaphylaxis (PCA) histamine release from mast cells, and the carrageenan-induced rat paw edema. To further characterize the active components, the water extract was either extracted with organic solvent or fractionated according to molecular weight, and each fraction was tested for some of anti-allergic parameters. Hyaluronidase activities, both in activating and in activated states, were significantly inhibited by the water extract of Cimicifuga heracleifolia and by some of its subfractions, molecular weight less than 1,000. The water extracts (50~400 mg/kg) significantly inhibited 48 hr homologous PCA and vascular permeability changes induced by chemical mediators (histamine, serotonin, and leukotriene $C_4$) in mice. In the case of histamine-induced vascular permeability changes, more extensive studies were conducted; water extract was either fractionated according to molecular weight or extracted with butanol. Anti-histamine actions were observed only from the water layer, and these active components were of the molecular weight less than 1,000. These anti-allergic actions were observed mainly from mice than from rats. On the other hand, anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were significant in rats.

• Journal of Applied Biological Chemistry
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• v.65 no.3
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• pp.167-172
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• 2022

Pathophysiological reaction of platelets in the blood vessel is an indispensable part of thrombosis and cardiovascular disease, which is the most common cause of death in the world. In this study, we performed in vitro assays to evaluate antiplatelet activity of artemether in human platelets and attempted to identify the mechanism responsible for protein phosphorylation. Artemether is a derivative of artemisinin, known as an active ingredient of Artemisia annua, which has been reported to be effective in treating malaria, and is known to function through antioxidant and metabolic enzyme inhibition. However, the role of artemether in platelet activation and aggregation and the mechanism of action of artemether in collagen-induced human platelets are not known until now. In this study, the effect of artesunate on collagen-induced human platelet aggregation was confirmed and the mechanism of action of artemether was clarified. Artemether inhibited the phosphorylation of PI3K/Akt and Mitogen-activated protein kinases, which are phosphoproteins that are known to act in the signal transduction process when platelets are activated. In addition, artemether decreased TXA₂ production and decreased granule secretion in platelets such as ATP and serotonin release. As a result, artemether strongly inhibited platelet aggregation induced by collagen, a strong aggregation inducer secreted from vascular endothelial cells, with an IC₅₀ of 157.92 μM. These results suggest that artemether has value as an effective antithrombotic agent for inhibiting the activation and aggregation of human platelets through vascular injury.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.1
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• pp.32-37
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• 2017

Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tertrahydro-N-methyl-1-naphthalenamine (sertraline) hydrochloride from among selective serotonin reuptake inhibitors (SSRIs) is a treatment of major depression. For the differential diagnosis by metabolizing serotonin in a patient with neurological disorders, the radiolabeled $^{11}C$-sertraline was developed for non-invasive positron emission tomography in living brain and use the evaluation of new drug for SSRIs. We release the results of a fast and easy radiolabeling method applied a one-step loop method with $[^{11}C]CH_3OTf$ for routine clinical applications of $^{11}C$-sertraline. 1 mg of a precursor for $^{11}C$-sertraline in 0.1 mL DMF and $5{\mu}L$ of 1N NaOH, were injected into the loop of semi-prep high-performance liquid chromatography (HPLC). $[^{11}C]CH_3OTf$ was passed through the loop at room temperature (RT). The $^{11}C$-sertraline was separated by the semi-preparative HPLC. $^{11}C$-sertraline was eluted at 28.0 min was collected and evaluated by analytical HPLC and mass spectrometer. The total radiolabeling efficiency of $^{11}C$-sertraline was $30.7{\pm}8.7%$. The specific activity was $64.8{\pm}51.4GBq/{\mu}mol$. The radiochemical and chemical purities were higher than 99%. The mass spectrum of the product showed m/z peaks at 307.1 (M+1), indicating the mass of sertraline. By the one-step loop method with $[^{11}C]CH_3OTf$, $^{11}C$-sertraline could be quickly and easily prepared for clinical application.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.99-107
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• 2017

A species of Cordyceps, an ingredient in Chinese traditional medicine well-known for its major component, cordycepin (3'-deoxyadenosine), has been known to have antiplatelet effects; however, its effects on regulation of phosphoprotein have not been fully elucidated. In this study, we investigated how cordycepin regulates the phosphoprotein, including phosphatidylinositol 3-kinase (PI3K)/Akt and p38, to inhibit platelet aggregation, which are concerned with fibrinogen binding to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}_3$) and granule secretion in platelets. Our finding suggests that cordycepin inhibits collagen-induced platelet aggregation with $261.1{\mu}M$ of $IC_{50}$ and also inhibits fibrinogen binding to ${\alpha}IIb/{\beta}_3$ by a suppression of PI3K/Akt phosphorylation in a dose dependent manner. In addition, cordycepin further showed to inhibit collagen-induced p38 phosphorylation, reducing granule secretion (i.e. ATP- and serotonin-release) and thromboxane $A_2$ ($TXA_2$) production without regulating cyclooxygenase-1 (COX-1) and thromboxane A synthase (TXAS) activities, as well as phospholipase $C-{\gamma}_2$ ($PLC-{\gamma}_2$) phosphorylation. In conclusion, these results demonstrate that cordycepin-mediated antiplatelet effects were due to the inhibition of fibrinogen binding to ${\alpha}IIb/{\beta}_3$ via the suppression of PI3K/Akt phosphorylation and inhibition of granule secretion & $TXA_2$ production by suppressing p38 phosphorylation. These results strongly indicate that cordycepin might have therapeutic or preventive potential for platelet aggregation-mediated disorders, regulating the phosphoprotein, including PI3K/Akt and p38.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.13 no.5
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• pp.2125-2132
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• 2012

Fluoxetine and tianeptine are commonly used as antidepressants (AD), and haloperidol and risperidone are widely used as antipsychotic drugs (APD), and it modulates various ion channels. TREK2 channel subfamily is very similar to physiological properties of TREK1 channel which can play important roles in the pathophysiology of mental disorders such as depression and schizophrenia, therefore, the pharmacological effect of psychiatric and depression drug on TREK2 channel may be similar to those of TREK1. Using the excised inside-out patch-clamp technique, we have examined the effects of APD and AD on cloned TREK2 channel expressed CHO cells. Fluoxetine (selective serotonin release inhibitor, SSRI) inhibited the TREK2 channel in a concentration-dependent manner ($IC_{50}$ $13{\mu}M$), whereas selective serotonin reuptake enhancer (SSRE) tianeptine increased without reducing the TREK2 channel activity. Haloperidol also inhibited the TREK2 channel in a concentration-dependent manner ($IC_{50}$ $44{\mu}M$), whereas even higher concentration ($100{\mu}M$) of risperidone did not completely inhibit on the activity. This study showed that TREK2 channel was preferentially blocked by fluoxetine rather than tianeptine, and inhibited by haloperidol rather than risperidone, suggesting differential effect of TREK2 channels by APD and AD may contribute to some mechanism of adverse side effects.