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

Jiiang Huei Jeng, Hui Lin Wu, Bor Ru Lin, Wan Hong Lan, Hsiao Hwa Chang, Yuan Soon Ho, Po Hsuen Lee, Ying Jan Wang, Juo Song Wang, Yi Jane Chen, Mei Chi Chang

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Abstract

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.

Original languageEnglish
Pages (from-to)250-258
Number of pages9
JournalAtherosclerosis
Volume191
Issue number2
DOIs
Publication statusPublished - 2007 Apr 1

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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    Jeng, J. H., Wu, H. L., Lin, B. R., Lan, W. H., Chang, H. H., Ho, Y. S., Lee, P. H., Wang, Y. J., Wang, J. S., Chen, Y. J., & Chang, M. C. (2007). Antiplatelet effect of sanguinarine is correlated to calcium mobilization, thromboxane and cAMP production. Atherosclerosis, 191(2), 250-258. https://doi.org/10.1016/j.atherosclerosis.2006.05.023