Anti-Thrombotic Effects of Artesunate through Regulation of cAMP and PI3K/MAPK Pathway on Human Platelets

• Published in: International journal of molecular sciences 2022-01, Vol.23 (3), p.1586
• Main Authors: Yoon, Shin-Sook, Kwon, Hyuk-Woo, Shin, Jung-Hae, Rhee, Man Hee, Park, Chang-Eun, Lee, Dong-Ha
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - adverse effects; Adenosine monophosphate; AKT protein; Alzheimer's disease; Arteriosclerosis; Artesunate; Artesunate - pharmacology; Atherosclerosis; Blood clots; Blood platelets; Calcium - metabolism; Calcium ions; Calcium mobilization; Cardiovascular disease; Cardiovascular diseases; Cell cycle; Cyclic AMP; Cyclic AMP - metabolism; Cyclic GMP; Cyclic GMP - metabolism; cyclic nucleotide; Disease prevention; Fibrinogen; Fibrinolytic Agents - pharmacology; Gene Expression Regulation - drug effects; granule secretion; Heart failure; Hemostasis; Hemostatics; Humans; Inositol 1,4,5-trisphosphate receptors; Inositols; intracellular Ca2; Kinases; MAP kinase; MAP Kinase Signaling System - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Plant extracts; Plant roots; Platelet aggregation; Platelet Aggregation - drug effects; Proteins; Serotonin; Signal transduction; Thrombosis; Thromboxane A2 - metabolism; Vasodilator-stimulated phosphoprotein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031586

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 or , 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 (IP R), substrates to cAMP-dependent kinase and cGMP-dependent kinase, in a significant manner. The Ca , normally mobilized from the dense tubular system, was inhibited due to IP R phosphorylation from artesunate, and phosphorylated VASP aided in inhibiting platelet activity via αIIb/β 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 TXA 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.