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Antiplatelet effect of sanguinarine is correlated to calcium mobilization; thromboxane and cAMP production

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題名:Antiplatelet effect of sanguinarine is correlated to calcium mobilization; thromboxane and cAMP production

作者:何元順

Jiiang-Huei Jeng; Hui-Lin Wu; Bor-Ru Lin; Wan-Hong Lan; Hsiao-Hwa Chang; Yuan-Soon Ho; Po-Hsuen Lee; Ying-Jan Wang; et. al.

貢獻者:醫學檢驗暨生物技術學系 上傳時間:2009-08-25T02:37:52Z

摘要:Sanguinarine is a plant alkaloid present in the root of Sanguinaria canadensis and Poppy fumaria species.

Sanguinarine has been used as an antiseptic mouth rinse and a toothpaste additive to reduce dental plaque and gingival inflammation. In this study, we investigated the antiplatelet effects of sanguinarine, aiming to extend its potential pharmacological applications. Sanguinarine inhibited platelet aggregation induced by arachidonic acid (AA), collagen, U46619 and

sub-threshold concentration of thrombin (0.05 U/ml) with IC(50) concentrations of 8.3, 7.7, 8.6 and 4.4 microM, respectively. Sanguinarine (5-10 microM) inhibited 10-31% of platelet TXB(2) production, but not platelet aggregation induced by higher concentration of thrombin (0.1 U/ml). SQ29548, a thromboxane receptor antagonist, inhibited the AA-induced platelet aggregation but not TXB(2) production. Sanguinarine suppressed

cyclooxygenase-1 (COX-1) activity (IC(50)=28 microM), whereas its effect on COX-2 activity was minimal. Sanguinarine (8, 10 microM) further inhibited the AA-induced Ca(2+) mobilization by 27-62%. In addition, SQ22536, an adenylate cyclase inhibitor, attenuated the inhibitory effect of sanguinarine toward AA-induced platelet Ca(2+) mobilization and aggregation. These results suggest that sanguinarine is a potent

antiplatelet agent, which activates adenylate cyclase, inhibits platelet Ca(2+) mobilization, TXB(2) production as well as suppresses COX-1 enzyme activity.

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Sanguinarine may have therapeutic potential for

treatment of cardiovascular diseases related to platelet aggregation.

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