# Antithrombotic Effects of Cordycepin-Enriched WIB-801CE via Inhibition of Thromboxane A2-Induced αIIbβ3 Activation and Thrombin-Mediated Fibrin Clot Retraction

## TL;DR

A Cordyceps extract inhibits platelet activation and clot formation, offering potential for treating blood clot disorders.

## Contribution

WIB-801CE is shown to inhibit thromboxane A2-induced platelet activation and clot retraction through specific protein phosphorylation modulation.

## Key findings

- WIB-801CE inhibits U46619-induced fibrinogen binding and platelet aggregation without cytotoxicity.
- The extract downregulates activating protein phosphorylation and upregulates inhibitory protein phosphorylation.
- WIB-801CE abolishes thrombin-induced fibrin clot retraction and shows antioxidant effects.

## Abstract

WIB-801CE, a standardized Cordyceps militaris extract containing 7.0% cordycepin, suppresses platelet activation induced by thrombin, collagen, and adenosine diphosphate (ADP). As these agonists generate thromboxane A2 (TXA2), which amplifies platelet activation via a self-propagating feedback loop, blockade of TXA2-mediated signaling offers strong antithrombotic potential. TXA2-antagonistic effects were evaluated using U46619, a stable TXA2 analog. Platelet activation was assessed by fibrinogen binding to integrin αIIbβ3, aggregation, and phosphorylation of platelet-activating proteins—PI3K (Tyr458), Akt (Ser473), p38 MAPK (Thr180/Tyr182), ERK1 (Thr202/Tyr204), JNK1 (Thr183/Tyr185)—and inhibitory proteins—VASP (Ser157) and IP3RI (Ser1756)—via immunoblotting. Thrombin-induced fibrin clot retraction, cytotoxicity, coagulation parameters, and antioxidant capacity were also examined. WIB-801CE significantly inhibited U46619-induced fibrinogen binding to integrin αIIbβ3 and platelet aggregation, without inducing cytotoxicity or impairing hemostatic function. It also significantly downregulated the phosphorylation of platelet-activating proteins and upregulated the phosphorylation of platelet-inhibiting proteins. Additionally, WIB-801CE abolished thrombin-induced fibrin clot retraction and demonstrated antioxidant capacity. WIB-801CE disrupts TXA2-driven platelet activation and thrombus stabilization by selectively modulating phosphorylation of key signaling proteins at defined regulatory sites. These properties highlight its promise as a therapeutic candidate for thrombotic disorders with platelet hyperreactivity.