• 생약학회지
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• 제17권1호
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• pp.19-22
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• 1986

As a continuation of the previous work, a second group of sixty solvent fractions prepared from twenty plant species were screened for their inhibitory effects on adenosine 5'-diphosphate (ADP)-, arachidonic acid (AA)- or collagen-induced rat platelet aggregation. The results suggested that five plant species including Angelica koreana, Cassia obtusifolia, Gastrodia elata, Paeonia lactiflora and Salvia miltiorrhiza are potential sources of inhibitors of platelet aggregation.

• 대한의생명과학회지
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• 제24권3호
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• pp.253-262
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• 2018

Platelets are activated at sites of vascular injury via several molecules, such as adenosine diphosphate, collagen and thrombin. Full platelet aggregation is absolutely essential for normal hemostasis. Moreover, this physiological event can trigger circulatory disorders, such as thrombosis, atherosclerosis, and cardiovascular disease. Therefore, platelet function inhibition is a promising approach in preventing platelet-mediated circulatory disease. Many studies reported the involvement of mitogen-activated protein kinases (MAPKs) signaling pathways in platelet functions. However, these studies were limited. Thus, we examined MAPK signaling pathways in human platelets using specific MAPK inhibitors, such as PD98059, SB203580, and SP600125. We observed that these inhibitors were involved in calcium mobilization and influx in human platelets. They also suppressed thrombin-induced ${\alpha}$- and ${\delta}$-granule release. These results suggest that PD98059, SB203580, and SP600125 exhibit $Ca^{2+}$ antagonistic effects.

• 생약학회지
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• 제18권4호
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• pp.203-206
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• 1987

An activity guided fractionation of the methanol extract of Cassiae Semen yielded three platelet anti-aggregatory components, aurantio-obtusin, chryso-obtusin and emodin.

• 대한의생명과학회지
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• 제27권3호
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• pp.170-176
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• 2021

Thapsigargin (TG), a sarco/endoplasmic reticulum (ER) Ca²⁺-ATPase (SERCA) inhibitor, has been widely used as an agonist for platelet aggregation for decades. In this study, we investigated the effect of TG on the release of lactate dehydrogenase (LDH) for platelets and elucidated its mechanism. Platelet LDH release and platelet aggregation were increased by TG treatment; 1,000 nM of TG induced the complete lysis of platelets. Other agonists such as collagen (2.5 ㎍/mL), thrombin (0.1 U/mL), and ADP (10 mM) did not induce significant platelet LDH release despite platelet aggregation. Finally, we investigated the effects of pharmacological inhibitors on TG-induced platelet aggregation and LDH release. SP600125, a JNK inhibitor, and LY294002, a PI-3K inhibitor, inhibited TG-induced platelet LDH release but not platelet aggregation. Forskolin, an adenylyl cyclase activator, also inhibited LDH release without affecting platelet aggregation by TG. These results suggest that the TG-induced platelet aggregation was accompanied by LDH release but regulated by a different signaling pathway.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.69-78
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• 2001

Cyclooxygenase (COX) is an enzyme, which catalyzes the production of prostaglandins from arachi-donic acid and exists in two isoforms (COX-1 and COX-2). COX-1 is involved in the maintenance of physiological functions such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. COX-2 is induced significantly in vivo under inflammatory conditions. COX-1 and COX-2 serve different physiological and pathological functions. All commercially available nonsteroidal antiinflammatory drugs (NSAIDS) are inhibitors of both COX-1 and COX-2. Therefore, selective inhibitors of COX-2 may be effective antiinflammatory agents without the ulcerogenic effects associated with current NSAms. Since the mid 1990s, a number of reports have been appeared on the preparation and biological activity of selective COX-2 inhibitors. Recently celecoxib, and rofecoxib, the representative COX-2 inhibitors, are introduced in the drug market. In this paper the relationship of structure-activity for selective COX-2 inhibitors is reviewed.

• 정신신체의학
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• 제29권2호
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• pp.153-161
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• 2021

연구목적 본 연구는 주요우울장애 환자들을 대상으로, 혈소판기능분석기(Platelet Function Analyzer, PFA-100)를 사용하여 선택적 세로토닌 재흡수 억제제(Selective Serotonin Reuptake Inhibitors, SSRI)와 세로토닌 노르에피네프린 재흡수 억제제(Serotonin Norepinephrine Reuptake Inhibitors, SNRI)의 출혈 경향성을 분석하고, 두 군 사이의 차이를 비교 분석하고자 하였다. 방 법 본 연구는 단일 기관에서 시행된 전향적 개방연구로 DSM-5 진단기준에 의해 주요우울장애로 진단받은 총 41명을 대상으로 하였다. 대상군을 무작위 배정에 따라 각각 SSRI (Escitalopram) 투여군과, SNRI (Duloxetine) 투여군으로 분류하였다. 각 항우울제를 투여 받기 전과 6주가 지난 시점에 혈소판기능분석기(Platelet Function Analyzer, PFA-100)를 이용하여 폐색시간(Closure Time, CT)을 측정하였다. 특정 항우울제가 폐색시간에 영향을 미치는지 알아보기 위해 각 군 내에서 대응표본 t-검정(Paired t-test)을 시행하였고, 두 군 사이에 혈소판 기능의 상대적인 변화를 확인하기 위해 공분산 분석(Analysis Of Covariance, ANCOVA)을 시행하여 두 군의 폐색시간의 변화를 비교 분석하였다. 결 과 SSRI군과 SNRI군에서 약물 투여 전과 6주후 폐색시간(CEPI-CT, CADP-CT)에 대한 유의한 변화는 없었고, 두 군 간의 폐색시간 변화량에도 차이가 없었다. 결 론 혈소판기능분석기(Platelet Function Analyzer, PFA-100)를 통해 SSRI인 Escitalopram과 SNRI인 Duloxetine간의 출혈경향성에 차이가 없음을 보였다. 향후 다양한 항우울제를 대상으로 출혈경향성에 대한 추가적인 대규모 연구가 필요할 것으로 보인다.

• Journal of Korean Neurosurgical Society
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• 제62권1호
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• pp.3-9
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• 2019

As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

• The Korean Journal of Physiology and Pharmacology
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• 제4권2호
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• pp.99-104
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• 2000

We investigated the action of NOS inhibitors on NOS in rats. Both of nitric oxide synthase inhibitors, $N^G$-monomethyl-L-arginine $(L-NMMA,\;3\;{\mu}M)$ or $N^G$-nitro-L-arginine methylester $(L-NAME,\;30\;{\mu}M),$ augmented phenylephrine $(PE,\;10^{-7}\;M)-induced$ contraction which was inhibited by acetylcholine (ACh) in rat thoracic aorta. This augmentation by L-NAME or L-NMMA was attenuated with the treatment of NO precursor, arginine. ACh, however, decreased the augmentation induced by L-NMMA, but not by L-NAME. Superoxide dismutase (SOD, 50 u/ml) potentiated an inhibitory effect of ACh on the PE $(10^{-7}\;M)-induced$ contraction. It has been known that platelet activating factor itself induces iNOS. Platelet activating factor $(PAF,\;10^{-7}\;M)$ inhibited PE $(10^{-7}\;M)-induced$ contraction. Pretreatment with L-NMMA (30 mM) or L-NAME (30 mM) significantly blocked the inhibitory action of PAF on PE-induced contraction. L-NMMA (100 mM) or L-NAME (100 mM) reduced nerve conduction velocity (NCV) relevant to nNOS in rat sciatic nerve. ACh attenuated the reduction of NCV by L-NMMA-, but not by L-NAME-induced reduction of NCV. These results suggest that L-NMMA and/or L-NAME have different action on three types of NOS in rats.

• 대한약리학회지
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• 제32권1호
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• pp.103-112
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• 1996

Platelet-activating factor (PAF)에 의하여 자극된 호중구 respiratory burst, 탈과립과 세포질 칼슘농도의 증가에 있어 protein kinase C와 protein tyrosine kinase의 역할을 관찰하였다. PAF에 의하여 자극된 호중구에서 superoxide 및 $H_2O_2$의 생성과 myeloperoxidase와 acid phosphatase의 유리는 protein kinase C 억제제인 staurosporine과 H-7 그리고 protein tyrosine kinase 억제제인 genistein과 tyrphostin에 의하여 억제되었다. PAF에 의한 호중구 세포내 칼슘농도의 증가는 staurosporine, genistein과 methyl-2,5-dihydroxycinnamate에 의하여 억제 되었다. Staurosporine은 PAF에 의하여 자극된 호중구에서 세포내 칼슘유리와 망간유입을 억제 하였다. Genistein과 methyl-2,5-dihydroxycinnamate는 PAF에 의한 망간유입을 억제하였으나, 세포내 칼슘유리에 대한 이들의 효과는 관찰되지 않았다. PMA에 의하여 활성화된 호중구에서 세포내 칼슘농도의 증가에 대한 PAF의 자극효과는 감소되었다. Protein kinase C와 protein tyrosine kinase는 PAF에 의하여 자극된 호중구에서의 respiratory burst, lysosomal enzyme유리와 칼슘동원에 관여할 것으로 제시된다. 세포내 칼슘농도의 증가는 protein kinase의 영향을 다르게 받는 세포내 칼슘유리와 세포외부로 부터의 칼슘유입에 의하여 이루어질 것으로 추정된다. Protein kinase C가 활성화되어 있는 상태에서 세포내 칼슘동원에 대한 PAF의 자극작용은 감소될 것으로 시사된다.

• 농업과학연구
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• 제24권2호
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• pp.267-274
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• 1997

산채류를 비롯한 식물자원으로부터 항혈전 성분을 탐색하기 위하여 전국일원의 농산시장 및 농촌지도소, 평창산채시험장과 한국인삼연초연구원의 실험포장으로부터 약 160점의 시료를 수집하였으며, modified smear method를 적용하여 그 methanol 추출물의 혈소판응집 저해활성을 비교하였다. Platelet rich plasma 즉 혈소판 혈장을 이용하는 modified smear method는 응집유도물질로서 ADP와 collagen을 사용하였을때 electrical impedence method와 높은 상관성을 나타내었고, 재현성도 비교적 우수하여 정제하지 않은 식물체의 조추출물의 항혈전 활성을 효율적으로 검색할 수 있었다. 참취, 개미취, 곤달비, 산마늘, 산도라지, 영양부추, 산뽕, 쇠비름, 생열귀등이 ADP와 collagen 모두 혈소판응집 저해활성을 나타내었으며, 곰취, 사철쑥, 씀바귀, 민들레, 산지치, 갯완두, 참대등은 collagen을 사용한 경우에는 저해활성이 다소 낮게 검출되었다. 반면에 참나물, 옥잠, 냉이, 메밀, 매실, 복분자, 해란초등은 오히려 혈소판응집 촉진효과를 나타내었다. 한편 DPPH법으로 활성산소 억제율을 비교한 결과 산채류중에는 고사리, 참취, 곰취, 구절초, 사철쑥, 고려엉겅퀴, 달개비, 냉이 그리고 생약재중에서는 적작약, 음양곽, 복분자등이 항산화활성이 높았다.