• 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.

• 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.

• Korean Journal of Pharmacognosy
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• v.18 no.4
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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.

• 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.

• 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.

• Korean Journal of Psychosomatic Medicine
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• v.29 no.2
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• pp.153-161
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• 2021

Objectives : The purpose of this study is to compare bleeding tendency of selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) using platelet function analyzer (PFA-100) in patients with major depressive disorder. Methods : This study is a prospective open-label study conducted by a single institution. A total of 41 subjects diagnosed with major depressive disorder under the DSM-5 diagnostic criteria participated in this study. The subjects were classified into SSRI (escitalopram) groups and SNRI (duloxetine) groups, respectively, according to random assignments. The closure time (CT) was measured using a platelet function analyzer (PFA-100) before each antidepressant was administered and after 6 weeks. Paired-sample t-test was conducted within each group to determine whether a specific antidepressant had an effect on closure time. In order to confirm the relative change in platelet function between the two groups, an independent sample t-test was conducted to compare and analyze the change in closure time between the two groups. Results : There was no significant changes in closure time (CEPI-CT, CADP-CT) before and 6 weeks after drug administration in the SSRI and SNRI groups, and there was no difference in the amount of changes in closure time between the two groups. Conclusions : Our results showed no difference in bleeding tendency between SSRI and SNRI. This study suggests that further large-scale studies on bleeding tendency for various antidepressants are needed in the future.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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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.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.103-112
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• 1996

Roles of protein kinase C and protein tyrosine kinase in the activation of neutrophil respiratory burst, degranulation and elevation of cytosolic $Ca^{2+}$ in platelet-activating factor (PAF)-stimulated neutrophils were investigated. Superoxide and $H_2O_2$ production and myeloperoxidase and acid phosphatase release in PAF-stimulated neutrophils were inhibited by protein kinase C inhibitors, staurosporine and H-7 and protein tyrosine kinase inhibitors, genistein and tyrphostin. The PAF-induced elevation of $[Ca^{2+}]_i$ in neutrophils was inhibited by staurosporine, genistein and methyl-2,5-dihydroxycinnamate. Staurosporine inhibited both intracellular $Ca^{2+}$ release and $Mn^{2+}$ influx in PAF-stimulated neutrophils. Genistein and methyl-2,5-dihydroxycinnamate inhibited $Mn^{2+}$ influx induced by PAF, whereas their effects on intracellular $Ca^{2+}$ release were not detected. In neutrophils preactivated by PMA, the stimulatory effect of PAF on the elevation of $[Ca^{2+}]_i$ was reduced. Protein kinase C and protein tyrosine kinase may be involved in respiratory burst, lysosomal enzyme release and $Ca^{2+}$ mobilization in PAF-stimulated neutrophils. The elevation of $[Ca^{2+}]_i$ appears to be accomplished by intracullular $Ca^{2+}$ release and $Ca^{2+}$ influx which are differently regulated by protein kinases. Preactivation of protein kinase C appears to attenuate the stimulatory action of PAF on intracellular $Ca^{2+}$ mobilization.

• 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.