Abstract
Normal activation of platelets and their aggregation are crucial for proper hemostasis. It appears that excessive or abnormal aggregation of platelets may bring about cardiovascular diseases such as stroke, atherosclerosis, and thrombosis. For this reason, finding a substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artesunate is a compound extracted from the plant roots of Artemisia or Scopolia, and its effects have shown to be promising in areas of anticancer and Alzheimer’s disease. However, the role and mechanisms by which artesunate affects the aggregation of platelets and the formation of a thrombus are currently not understood. This study examines the ways artesunate affects the aggregation of platelets and the formation of a thrombus on platelets induced by U46619. As a result, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) production were increased significantly by artesunate relative to the doses, as well as phosphorylated vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP3R), substrates to cAMP-dependent kinase and cGMP-dependent kinase, in a significant manner. The Ca2+, normally mobilized from the dense tubular system, was inhibited due to IP3R phosphorylation from artesunate, and phosphorylated VASP aided in inhibiting platelet activity via αIIb/β3 platelet membrane inactivation and inhibiting fibrinogen binding. In addition, MAPK and PI3K/Akt phosphorylation was inhibited via artesunate in a significant manner, causing the production of TXA2 and intracellular granular secretion (serotonin and ATP release) to be reduced. Therefore, we suggest that artesunate has value as a substance that inhibits platelet aggregation and thrombus formation through an antiplatelet mechanism.
Highlights
IntroductionThe most prevalent cause of death is cardiovascular disease (CVD). TheUnited States reported that one in seven deaths were due to coronary heart disease and one in nine deaths were due to heart failure [1]
Worldwide, the most prevalent cause of death is cardiovascular disease (CVD)
To bring an understanding to the antiplatelet effect of artesunate, we investigated the effect of artesunate on calcium mobilization and granule secretion by examining the regulation of circulating nucleotides via the regulation of PI3K/Akt and Mitogen-activated protein kinases (MAPK)
Summary
The most prevalent cause of death is cardiovascular disease (CVD). TheUnited States reported that one in seven deaths were due to coronary heart disease and one in nine deaths were due to heart failure [1]. The most prevalent cause of death is cardiovascular disease (CVD). Excessive activation and aggregation of platelets is a major cause of thrombus formation that causes cardiovascular diseases such as coronary artery disease, atherosclerosis, heart failure, and stroke [2]. Thrombotic events are dramatically lowered through the inhibition of platelets via pharmacological agents, and CVD treatment and prevention uses such clinical drugs. Complications and side effects such as gastric bleeding, aplastic anemia, or even thrombocytopenia can arise from these drugs, often minimizing the benefits. They require the development of minimal prophylactic or therapeutic alternatives [3]. Many products that are natural, such as traditional diets from the Mediterranean and plants with medicinal purposes, have shown antiplatelet and cardioprotective properties in the prevention (primary and secondary) of CVD [5,6,7]
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