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

Add time:08/06/2019    Source:sciencedirect.com

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 IC50 concentrations of 8.3, 7.7, 8.6 and 4.4 μM, respectively. Sanguinarine (5–10 μM) inhibited 10–31% of platelet TXB2 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 TXB2 production. Sanguinarine suppressed cyclooxygenase-1 (COX-1) activity (IC50 = 28 μM), whereas its effect on COX-2 activity was minimal. Sanguinarine (8, 10 μM) further inhibited the AA-induced Ca2+ mobilization by 27–62%. In addition, SQ22536, an adenylate cyclase inhibitor, attenuated the inhibitory effect of sanguinarine toward AA-induced platelet Ca2+ mobilization and aggregation. These results suggest that sanguinarine is a potent antiplatelet agent, which activates adenylate cyclase, inhibits platelet Ca2+ mobilization, TXB2 production as well as suppresses COX-1 enzyme activity. Sanguinarine may have therapeutic potential for treatment of cardiovascular diseases related to platelet aggregation.

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