Pharmacological Actions of 5-Hydroxyindolin-2 on Modulation of Platelet Functions and Thrombus Formation via Thromboxane A2 Inhibition and cAMP Production

Platelets play a very significant role in hemostasis while simultaneously posing a risk for the development of various cardiovascular diseases. Platelet-mediated issues can occur in blood vessels and trigger various medical problems. Therefore, controlling platelet function is important in the prevention of thrombosis. In this regard, we need to find compounds that provide potent antiplatelet activity with minimum side effects. Therefore, we examined the effect of 5-hydroxyindolin-2-one isolated from Protaetia brevitarsis larvae having antiplatelet properties and investigated different pathways that mediate the antiplatelet activity. We examined the effect of 5-hydroxyindolin-2-one (5-HI) on the regulation of phosphoproteins, thromboxane A(2) generation, and integrin alpha IIb beta 3 action. Our data showed that human platelet aggregation was inhibited by 5-HI (75, 100, 150, 200 mu M) without cytotoxicity, and it suppressed intracellular Ca2+ concentration through the regulation of inositol 1, 4, 5-triphosphate receptor I (Ser(1756)) and extracellular signal-regulated kinase (ERK). Moreover, collagen-elevated thromboxane A(2) production and alpha IIb beta 3 action were inhibited by 5-HI through the regulation of cytosolic phospholipase A(2) (cPLA(2)), mitogen-activated protein kinase p38 (p38(MAPK)), vasodilator-stimulated phosphoprotein (VASP), phosphoinositide 3-kinase (PI3K), and Akt (protein kinase B). Therefore, we suggested that 5-HI could be a potential substance for the prevention of thrombosis-mediated thrombosis.

Automated summary

Platelets play a significant role in hemostasis but can also contribute to the development of cardiovascular diseases. Controlling platelet function is important in preventing thrombosis. A compound called 5-hydroxyindolin-2-one (5-HI) has been found to inhibit human platelet aggregation without cytotoxicity and suppress intracellular Ca2+ concentration. It also regulates various pathways to inhibit thromboxane A(2) production and alpha IIb beta 3 action, suggesting its potential as a substance for preventing thrombosis-mediated thrombosis.