• 생약학회지
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• 제52권1호
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• pp.26-33
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• 2021

During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.

• 대한약리학회지
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• 제11권1호
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• pp.33-38
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• 1975

말정혈관확장제(末精血管擴張劑)인 Ethaverine의 임상효과(임상(臨床效果)는 말초동맥질환(末梢動脈疾患)을 갖인 29명(名)의 당뇨질환자(糖尿疾患者)를 대상으로 이중맹검(二重盲檢) 비교차(非交叉) 방법(方法)에 의(依)하여 연구검토(硏究檢討)하였다. 임상적(臨床的)인 개선(改善)은 간헐성파행증(間歇性跛行症)의 발생빈도(發生頻度)를 포함하는 환노(患老)들의 병역(病歷)으로부터 평가(評價)하였다. Ethaverine을 사주(四週) 치료후(治療後)는 임상증상(臨床症狀)을 개선(改善)하는데 있어 위약(僞藥)에 비(比)하여 효과가 없었다. 어째든 간에 Ethaverine은 위약(僞藥)보다는 혈관확장제(血管擴張劑)로서 효력이 있었다. Ethaverine에 의(依)하여 유발(誘發)되는 혈관확장제(血管擴張劑)의 성질(性質)은 alcohol의 그것과 유사하였다. 말초혈관확장제(末梢血管擴張劑)를 연구(硏究)하는 새로운 임상적(臨床的) 방법(方法)을 제시(提示)하였다. 하지(下肢)의 말초혈관(末梢血管) 동맥질환(動脈疾患)의 임상증상(臨床症狀)은 촉맥강도(觸脈强度)의 감소냉감(減少冷感) 및 피부(皮膚)의 변색(變色)등을 들 수 있다. 간헐성파행증(間歇性跛行症)도 수반하는 수가 있다. 혈관조직(血管組織)에 있어서의 병변(病變)이 이같은 증상(症狀)에 선행(先行)하여 일어나며 위중(危重)한 혈관부전(血管不全)의 입증(立證)은 혈관확장제료법(血管擴張劑療法) 또는 외과적(外科的) 처치(處置)를 택하는데 있어서의 결정적(決定的)인 요인(要因)이 된다. 만성 말초동맥질환(末梢動脈疾患)이 있는 술후환자(術後患者)들도 차후혈관확장제(次後血管擴張劑)의 치료(治療)를 받아야한다. 임상보고((臨床報告)에 의(依)하면 말초혈관확장제(末梢血管擴張劑)는 폐새성(閉塞性) 혈관질환(血管疾患)에 대(對)해서 보다는 혈관경련성(血管痙攣性) 말초혈관장해(末梢血管障害)에 대해서 보다 유효하며 비교적 큰 혈관상(血管床)보다는 작은 모세혈관상(毛細血管床) 일때의 혈관(血管)이 가장 잘 감응(感應)한다고 한다. 최근(最近)에 이르러 말초혈관확장제(末梢血管擴張劑)의 임상(臨床)효과는 수많은 임상연구가(臨床硏究家)들 및 임상의(臨床醫)들의 연구대상(硏究對象)이 되고있다. 본연구(本硏究)에서 연구자(硏究者)들은 혈관경련성말초동맥질환(血管痙攣性末梢動脈疾患)을 갖인 환자(患者)들에 대(對)한 말초혈관확장제(末梢血管擴張劑)로써의 Ethaverine HCl의 임상(臨床)효과를 재평가(再評價)하였다. Ethaverine은 각종임상시험결과(各種臨床試驗結果)에 의(依)하면 항경련제(抗痙攣劑)로서는 papaverine 보다도 2배(倍) 내지 4배(倍)정도 그 약효가 강력(强力)하다고 한다.

• 한국산학기술학회논문지
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• 제20권12호
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• pp.298-305
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• 2019

꾸지뽕나무 뿌리 추출물은 항염, 항암, 항산화와 같은 효과를 갖는 많은 생리활성 물질을 포함하고 있다고 알려져 있다. 그러나 꾸지뽕나무 뿌리 추출물(이하 CTE)의 사람 혈소판 응집 억제 기전에 관하여는 알려진 바 없다. 본 연구에서는 CTE가 혈소판에 미치는 영향을 확인하고자 하였다. CTE는 collagen으로 유도한 혈소판 응집 반응에서 cyclooxygenase-1 활성을 억제하고, 세포 내 칼슘 농도를 낮추는 방식으로 thromboxane A₂ 생성을 억제하였다. 또한, phospholipase Cγ2와 syk의 인산화 반응을 억제하였으며, guanosine monophosphate (cGMP)에 의존적인 방식으로 vasodilator-stimulated phosphoprotein(VASP)의 Ser²³⁹ 위치를 인산화하여 항혈소판 효과를 나타내었다. 또한, 고지방 식이로 혈소판 활성화를 유도한 랫드에서 CTE를 경구 투여 하였을 때, 간독성 없이 콜라겐으로 유도한 혈소판 응집반응을 thromboxane A₂ 생성을 억제함으로써 항혈소판 효과를 보였다. 이는 in vivo와 in vitro에서 같은 결과를 제시하고 있다. 결론적으로, CTE는 항혈소판 작용 및 심혈관계 질환 예방을 위한 천연물 유래의 안전하고, 새로운 물질임을 제시하는 바이다.

• Journal of Ginseng Research
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• 제37권2호
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• pp.176-186
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• 2013

In this study, we have investigated the effects of total saponin from Korean red ginseng (TSKRG) on thrombin-induced platelet aggregation. TSKRG dose-dependently inhibited thrombin-induced platelet aggregation with $IC_{50}$ value of about 81.1 ${\mu}g/mL$. In addition, TSKRG dose-dependently decreased thrombin-elevated the level of cytosolic-free $Ca^{2+}$ ($[Ca^{2+}]_i$), one of aggregation-inducing molecules. Of two $Ca^{2+}$-antagonistic cyclic nucleotides as aggregation-inhibiting molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), TSKRG significantly dose-dependently elevated intracellular level of cAMP, but not cGMP. In addition, TSKRG dose-dependently inhibited thrombin-elevated adenosine triphosphate (ATP) release from platelets. These results suggest that the suppression of $[Ca^{2+}]_i$ elevation, and of ATP release by TSKRG are associated with upregulation of cAMP. TSKRG elevated the phosphorylation of vasodilator-stimulated phosphoprotein (VASP)-$Ser^{157}$, a cAMP-dependent protein kinase (A-kinase) substrate, but not the phosphorylation of VASP-$Ser^{239}$, a cGMP-dependent protein kinase substrate, in thrombin-activated platelets. We demonstrate that TSKRG involves in increase of cAMP level and subsequent elevation of VASP-$Ser^{157}$ phosphorylation through A-kinase activation to inhibit $[Ca^{2+}]_i$ mobilization and ATP release in thrombin-induced platelet aggregation. These results strongly indicate that TSKRG is a beneficial herbal substance elevating cAMP level in thrombin-platelet interaction, which may result in preventing of platelet aggregation-mediated thrombotic diseases.

• Journal of Chest Surgery
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• 제18권4호
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• pp.732-739
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• 1985

This study was experimentally undertaken to evaluate the effect of the coronary vasodilator-mixed cardioplegic solution on myocardial protection during prolonged aortic cross-clamping. The dogs were divided into two groups: control group A[received hypothermic cardioplegic solution without any additive coronary vasodilator], and comparing group 8[received hypothermic cardioplegic solution, mixed with various coronary vasodilators and Inderal]. Group A further was divided into two subgroups: subgroup A-1[ischemic time, 90 minutes], and subgroup A-2 [ischemic time, 240 minutes]. Group B further was divided into five subgroups: subgroup B-1 [received papaverine mixed hypothermic cardioplegic solution], subgroup B-2[received nitroglycerin mixed hypothermic cardioplegic solution], subgroup B-3 [received nitroprusside mixed hypothermic cardioplegic solution, subgroup B-4[received hydralazine mixed hypothermic cardioplegic solution], and subgroup B-5 [received inderal mixed hypothermic cardioplegic solution]. The specimens from all of the subgroups were studied by electron microscopic examination. The specimens of subgroups [B-l, B-2 8-3, and B-4], received coronary vasodilators mixed hypothermic cardioplegic solutions, were also compared by methylene blue induced staining of the myocardium and coronary vessels. The results obtained were as followings: l. On electron microscopic examination, all of the specimens, including subgroup A-2, showed no irreversible change of the myocardium. But the best result was obtained from the subgroup B-l, treated by papaverine mixed hypothermic cardioplegic solution. The subgroup B-2, treated by nitroglycerin, was next. And the subgroup B-5, treated by Inderal, was agreeable, comparing the electron microscopic finding with control group in the effect of myocardial protection. 2. The distribution in the myocardium of cardioplegic solution was demonstrated with the aid of methylene blue staining in the subgroups of B-l, B-2, B-3, and B-4, and they were the groups treated by papaverine, nitroglycerin, nitroprusside, and hydralazine in their grouping order. The best result was obtained from the subgroup B-1 [papaverine]. The subgroup B-2 [nitroglycerin] was next. The subgroup B-3 [nitroprusside] was moderate in finding of the colorization. The subgroup B-4 [hydralazine] was the poorest in the distribution of the cardioplegic solution in the myocardium. From these results, it appeared that myocardial protection during ischemic arrest for open heart surgery could be enhanced considerably when coronary dilatation was assured.

• Journal of Yeungnam Medical Science
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• 제26권2호
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• pp.93-101
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• 2009

The use of magnesium sulphate has recently increased in anesthesiology and pain medicine. The roles of magnesium sulphate are as an analgesic adjuvant, a vasodilator, a calcium channel blocker and reducing the anesthetic requirement. These effect are primarily based on the regulation of calcium influx into the cell and antagonism of the N-methyl-D-aspartate receptor. We discuss here the clinical effects of magnesium sulphate on anesthesiology and pain medicine.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.202.2-202.2
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• 2003

Rg3 is a derivative of triterpenoid dammarane, which originally extracted from Red Ginseng, which have been known to have neuroprotective, vasodilator, antioxidative, antimetastasis, and direct anticancer effects. These various backgrounds of Rg3 can provide an additional interest in respect to the “hematopoiesis” in bone marrow and spleen cells. We, therefore, have investigated what effects and correlates of Rg3 (e.g. suppression and side effects) are affected in relation with the bone marrow and spleen cells of mouse. (omitted)

• Journal of Nutrition and Health
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• 제38권2호
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• pp.89-95
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• 2005

This study was performed to investigate the effect of soy isoflavone on plasma nitrite concentration and the antioxidant enzyme activities of erythrocyte and the liver using adult male rats fed high fat diet. Seven-week old male Sprague Dawley rats were divided into three groups and fed high fat diet (15% beef tallow, 1 % cholesterol; control: IF0) or high fat diets containing isoflavone 80 ppm (IF80) or 320 ppm (IF320) for 10 weeks. Plasma nitrite concentration as a vasodilator, and antioxidant enzyme activities in erythrocytes and the liver were measured. Plasma nitrite concentration was increased by 45% and 35%, respectively, in IF80 and IF320 than in IF0 group. Erythrocyte catalase, glutathione peroxidase (GPx) and glutathione reductase (GR) activities increased by 31 %, 30% and 40% in IF320 compared to IF0 group. Especially, erythrocyte GR activity increased by 61 % in IF80 group. However, catalase activity in the liver was decreased in IF80 group. GPx and GR activities in the liver were not differ among groups. The results suggest that soy isoflavone have the protective effect against risk factors related with cardiovascular disease by improving vasodilator factor, nitrite, and antioxidant enzyme activities in blood. (Korean J Nutrition 38(2): 89～95, 2005)

• The Korean Journal of Pain
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• 제5권2호
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• pp.234-238
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• 1992

돌발성 난청 환자의 혈관 확장치료로서 histamine을 사용한 군과 SGB를 사용한 군을 회고적으로 비교한 결과 Histamine군에서는 19예 가운데 10예(52.8%), SGB군 30예 중 17예(56.1%)에 있어서 2~3주 이내에 개선을 보였다. SGB는 금기증이 거의 없으며 수기가 간단하고 부작용이 경미하므로 돌발성 난청의 치료에 있어서 histamine 치료의 좋은 대치 방법이 될 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.573-580
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• 1998

The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.