Eisenia bicyclis (brown alga) modulates platelet function and inhibits thrombus formation via impaired P2Y12 receptor signaling pathway

Abstract

Background and purpose: Sea weeds have been used since ancient times in Asian countries, especially in Korea, Japan, and China, as both edible sea vegetables and traditional medicinal tonics due to their health benefits. Eisenia bicyclis has been studied for anti-allergic and anti-cancer effects; however, its effects on the cardiovascular system, especially on platelet function, are yet to be explored. Therefore, we examined the effect of E. bicyclis on platelet function.

Study design and methods: E. bicyclis extract (EBE) was prepared and in vitro effects on ADP-induced platelet aggregation, granule secretion, intracellular calcium ion ([Ca²⁺]_i) mobilization, fibrinogen binding to integrin α_IIbβ₃ and clot retraction were evaluated. Phosphorylation levels of MAPK signaling molecules and P₂Y₁₂ receptor downstream signaling pathway components were studied. In vivo effects were studied using an arteriovenous (AV) shunt model.

Results: EBE markedly inhibited in vitro ADP-induced platelet aggregation, granule secretion (ATP release and P-selectin expression), [Ca²⁺]_i mobilization, fibrinogen binding to integrin α_IIbβ₃, and clot retraction; attenuated MAPK pathway activation; and inhibited phosphorylation of PI3K/Akt, PLCγ2, and Src. The extract significantly inhibited in vivo thrombus weight in an AV shunt model.

Conclusion: E. bicyclis inhibits agonist-induced platelet activation and thrombus formation through modulation of the P₂Y₁₂ receptor downstream signaling pathway, suggesting its therapeutic potential in ethnomedicinal applications as an anti-platelet and anti-thrombotic compound to prevent cardiovascular diseases.

Keywords: Eisenia bicyclis; MAPK; Natural anti-thrombotic agent; P(2)Y(12) receptor; Platelet.