• Title/Summary/Keyword: Platelet aggregation inhibitors

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Screening of Potential Inhibitors of Platelet Aggregation from Plant Sources(II) (혈소판 응집 억제 작용 생약의 검색(II))

  • YunChoi, Hye-Sook;Kim, Jae-Hoon;Lee, Jong-Ran
    • Korean Journal of Pharmacognosy
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    • v.17 no.1
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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.

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Thapsigargin Induces Platelet Aggregation, thereby Releases Lactate Dehydrogenase from Rat Platelets

  • Baik, Ji Sue;Seo, You Na;Rhee, Man Hee;Park, Moon-Taek;Kim, Sung Dae
    • Biomedical Science Letters
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    • v.27 no.3
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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.

Detection of Platelet Aggregation Inhibitors and Fibrinolytic Substances from Mushrooms (버섯류로부터 혈소판 응집억제물질과 혈전용해물질의 탐색)

  • Park, Jeong-Sik;Hyun, Kwang-Wook;Seo, Seung-Bo;Cho, Soo-Muk;Yoo, Chang-Hyun;Lee, Jong-Soo
    • The Korean Journal of Mycology
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    • v.31 no.2
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    • pp.114-116
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    • 2003
  • Platelet aggregation inhibitory and fibrinolytic activities of water and ethanol extracts from mushrooms were studied. The highest platelet aggregation inhibitory activity was 81.2% in the ethanol extract from fruiting body of Inonotus obliquus ASI 74006 and also were high in the ethanol extract from fruiting bodies of Fomitella fraxinea. The ethanol extract from the mycelia of Agaricus blazei Murill. ASI 1174 showed the strongest fibrinolytic activity as 9.6 unit. However fibrinolytic activities of other mushrooms were low or negligible.

Inhibitory Effects of PD98059, SB203580, and SP600125 on α-and δ-granule Release and Intracellular Ca2+ Levels in Human Platelets

  • Kwon, Hyuk-Woo
    • Biomedical Science Letters
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    • v.24 no.3
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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.

Screening of Inhibitors of Platelet Aggregation from Edible Plants (산채류로부터 혈소판응집 억제물질의 검색)

  • Yoon, Min-Ho;Lim, Chi-Hwan;Oh, Jin-Hwan;Lee, Jong-Chul;Choi, Woo-Young
    • Korean Journal of Agricultural Science
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    • v.24 no.2
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    • pp.267-274
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    • 1997
  • To select potential inhibitors of platelet aggregation from large numbers of crude plant extracts, the modified thin smear method for the anti-platelet aggregating activity using platelet rich plasma was further modified by direct observation under a light microscope without staining the smear. The activities determined by the method were coincided with those by the electrical impedence method using whole blood, when ADP or collagen was employed as the aggregating agent. Among 130 varieties of edible and herbal plants which collected from markets or experimental farms of agricultural research institutes, those showed the anti-platelet aggregating activities were selected by testing the crude methanol extracts: Aster scaber, Aster tataricus, Ligularia stenocephala, Platycodon glaucum Allium victorialis, Allium oderum, Moros bombycis, Portulaco oleracea, Aamthopanax sessiliflorus and Rosa davurica. However, some of them activated the platelet aggregation under the same assay conditions: Pimpinella brachycarpa, Hosta plantaginea, Capsella bursapastoris, Fagopyrm esculentum, Prunus mume, Rubus coreanus and Limaria japonica. In addition, those revealed the antioxidant activities were selected by measuring the abilities to scavenge superoxide anion radicals: Pteridium aquilinum, Aster scaber, Ligularia fischeri, Chrysanthemum zawadskii, Artemisia capipparis, Cirsium setidens, Commelina communis and Capsella bursapastoris among edible plants.

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SAR of COX-2 Inhibitors (COX-2 억제제의 구조-활성)

  • 권순경
    • Biomolecules & Therapeutics
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    • v.9 no.2
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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.

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Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure

  • Yi, Ho Jun;Hwang, Gyojun;Lee, Byoung Hun
    • Journal of Korean Neurosurgical Society
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    • v.62 no.1
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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.

PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation

  • Kim, Sun-Young;Kim, Se-Woon;Kim, Jeong-Mi;Jho, Eek-Hoon;Park, Seon-Yang;Oh, Do-Yeun;Yun-Choi, Hye-Sook
    • BMB Reports
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    • v.44 no.2
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    • pp.140-145
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    • 2011
  • Impaired responsiveness of platelets to epinephrine (epi) and other catecholamines (CA) has been reported in approximately 20% of the healthy Korean and Japanese populations. In the present study, platelet aggregation induced by epi was potentiated by RO 31-8220 (RO) or G$\ddot{o}$ 6983 (G$\ddot{o}$). Phosphorylated Akt (p-Akt) was very low in epi-stimulated PRP from CA-hypo- responders (CA-HY), whereas it was detected in those from CA-good responders (CA-GR). RO and G$\ddot{o}$ increased p-Akt, one of the major downstream effectors of phosphoinositol-3 kinase (PI3K), in epi-stimulated PRP from both groups. Wortmannin, a PI3K inhibitor, attenuated the RO or G$\ddot{o}$-induced potentiation of p-Akt in epi-stimulated PRP, suggesting positive effects for RO and G$\ddot{o}$ on PI3K. $TXA_2$ formation was increased by the addition of either RO or G$\ddot{o}$ in epi-stimulated platelets. The present data also suggest that impaired Akt phosphorylation may be responsible for epinephrine hypo-responsiveness of platelets.

Snake Venom Phospholipase A2 and its Natural Inhibitors

  • Singh, Pushpendra;Yasir, Mohammad;Khare, Ruchi;Tripathi, Manish Kumar;Shrivastava, Rahul
    • Natural Product Sciences
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    • v.26 no.4
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    • pp.259-267
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    • 2020
  • Snakebite is a severe medical, economic, and social problem across the world, mostly in the tropical and subtropical area. These regions of the globe have typical of the world's venomous snakes present where access to prompt treatment is limited or not available. Snake venom is a complex mixture of toxin proteins like neurotoxin and cardiotoxin, and other enzymes like phospholipase A2 (PLA2), haemorrhaging, transaminase, hyaluronidase, phosphodiesterase, acetylcholinesterase, cytolytic and necrotic toxins. Snake venom shows a wide range of biological effects like anticoagulation or platelet aggregation, hemolysis, hypotension and edema. Phospholipase A2 is the principal constituent of snake venom; it catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid, which is the precursor of eicosanoids including prostaglandins and leukotrienes. The information regarding the structure and function of the phospholipase A2 enzyme may help in treating the snakebite victims. This review article constitutes a brief description of the structure, types, mechanism occurrence, and tests of phospholipase A2 and role of components of medicinal plants used to inhibit phospholipase A2.