Effects of DK-002, a synthesized (6aS,cis)-9,10-Dimethoxy-7,11b-dihydro-indeno[2,1-c]chromene-3,6a-diol, on platelet activity |
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Authors: | Lee Ki-Seon Khil Lee-Yong Chae Sang-Ho Kim Deukjoon Lee Byung-Hoon Hwang Gwi-Seo Moon Chang-Hyun Chang Tong-Shin Moon Chang-Kiu |
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Institution: | a Department of Preventive Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea b College of Oriental Medicine, Kyung Won University, Seongnam, 461-701, Korea c Department of Physiology, School of Medicine, Ajou University, Suwon, 442-749, Korea d Division of Molecular Life Sciences, Ewha Womans University, Seoul 120-750, Korea |
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Abstract: | In the present study, the mechanism of antiplatelet activity of DK-002, a synthesized (6aS,cis)-9,10-Dimethoxy-7,11b-dihydro-indeno2,1-c]chromene-3,6a-diol, was investigated. DK-002 inhibited the thrombin, collagen, and ADP-induced rat platelet aggregation in a concentration-dependent manner, with IC50 values of 120, 27, and 47 μM, respectively. DK-002 also inhibited thrombin-induced dense granule secretion, thromboxane A2 synthesis, and Ca2+]i elevation in platelets. DK-002 did not show any significant effect on ADP-induced inhibition of cyclic AMP elevation by prostaglandin E1, but DK-002 was confirmed to inhibit ADP-induced Ca2+]i elevation and shape change. DK-002 inhibited 4-bromo-A23187-induced Ca2+]i elevation in the presence of creatine phosphate/creatine phosphokinase (CP/CPK, a ADP scavenging system) and indomethacin (a specific inhibitor of cyclooxygenase). DK-002 also inhibited Ca2+ mobilization in thrombin- or 4-bromo-A23187-stimulated platelets through its inhibitory effects on both Ca2+ release from intracellular stores and Ca2+ influx, in the presence of CP/CPK and indomethacin. Taken together, the present study shows that DK-002 has inhibitory effects on stimulation of platelets, and suggests that its antiplatelet activity might be related to the inhibitory mechanism on Ca2+ mobilization in stimulated platelets. |
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Keywords: | Antiplatelet agent Brazilin derivative Calcium mobilization Platelet aggregation |
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