Tanshinone IIA impairs platelet function and thrombus formation.
Source: PubMed, NCBI / U.S. National Library of Medicine
Tanshinone IIA (T-IIA) is a fat-soluble active ingredient derived from the traditional Chinese medicine Danshen and possesses cardioprotective property. However, its exact role in platelet function is unknown. This study investigated T-IIA's role in platelet aggregation, granules release, spreading, clot retraction as well as in vivo hemostasis and thrombus formation. Human platelets were treated with different doses of T-IIA (10, 50, and 100 μM) to measure platelet function and activation. In addition, T-IIA was administrated into wild-type mice to evaluate hemostasis and thrombus formation. T-IIA significantly impaired platelet aggregation, ATP secretion, P-selectin expression, spreading and clot retraction dose-dependently without affecting the expression profiles of αIIbβ3, GPVI, or GPIbα. Administration of T-IIA significantly prolonged mice tail bleeding time and inhibited arterial and venous thrombosis. Further analysis showed that T-IIA dose-dependently reduced platelet ROS generation. Quantitative proteomic and phosphoproteimic assays analyzing T-IIA-treated versus vehicle-treated platelets after stimulation identified dysregulated phosphorylation of several proteins, which were enriched in platelet activation. Among the downregulated phosphoproteins, Rho-associated protein kinase 1 (ROCK1), integrin β3 and talin1 exhibited the lower fold change of phosphorylation in T-IIA-treated platelets compared to vehicle. Consistently, T-IIA treatme
Abstract
Tanshinone IIA (T-IIA) is a fat-soluble active ingredient derived from the traditional Chinese medicine Danshen and possesses cardioprotective property. However, its exact role in platelet function is unknown. This study investigated T-IIA's role in platelet aggregation, granules release, spreading, clot retraction as well as in vivo hemostasis and thrombus formation. Human platelets were treated with different doses of T-IIA (10, 50, and 100 μM) to measure platelet function and activation. In addition, T-IIA was administrated into wild-type mice to evaluate hemostasis and thrombus formation. T-IIA significantly impaired platelet aggregation, ATP secretion, P-selectin expression, spreading and clot retraction dose-dependently without affecting the expression profiles of αIIbβ3, GPVI, or GPIbα. Administration of T-IIA significantly prolonged mice tail bleeding time and inhibited arterial and venous thrombosis. Further analysis showed that T-IIA dose-dependently reduced platelet ROS generation. Quantitative proteomic and phosphoproteimic assays analyzing T-IIA-treated versus vehicle-treated platelets after stimulation identified dysregulated phosphorylation of several proteins, which were enriched in platelet activation. Among the downregulated phosphoproteins, Rho-associated protein kinase 1 (ROCK1), integrin β3 and talin1 exhibited the lower fold change of phosphorylation in T-IIA-treated platelets compared to vehicle. Consistently, T-IIA treatment inhibited the phosphorylation of ROCK1, p47phox, integrin β3 and talin1 in activated platelets. Tanshinone IIA impairs platelet function and thrombosis via inhibition of several signaling pathways including ROCK1/p47phox, β3 and talin1, implying that tanshinone IIA may represent a promising therapeutic candidate for treating thrombotic diseases.