Anti-thrombotic effects of arteanoflavone by regulating cyclic nucleotides and aggregation on human platelets

Abstract

Abstract Excessive clotting or abnormal platelet accumulation can lead to serious cardiovascular disorders such as atherosclerosis, stroke, and thrombosis. Therefore, it is imperative to identify compounds capable of controlling or impeding platelet aggregation to prevent the onset of cardiovascular diseases. Arteanoflavone, a compound extracted from Artemisia iwayomogi, has not garnered scientific recognition for its potential health benefits, recent studies have substantiated its anti-inflammatory, antioxidant, and anti-allergic properties. However, the precise mechanisms by which arteanoflavone influences platelet aggregation and blood clot formation have not been conclusively established. This research investigates arteanoflavone’s role in these processes, particularly in platelets induced by collagen. The study reveals a significant increase in the production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) correlating with the administered dosage of arteanoflavone. Concurrently, a noticeable escalation is observed in substrates of cAMP-dependent kinase and cGMP-dependent kinase, specifically VASP and inositol 1,4,5-trisphosphate receptor (IP3R). Arteanoflavone demonstrates its ability to limit Ca2+ movement in the dense tubular system through IP3R phosphorylation. Moreover, phosphorylated VASP inhibits the binding of fibrinogen to αIIb/β3, thus suppressing platelet activity. Arteanoflavone also stimulates the phosphorylation of PI3K/Akt, a protein linked to platelet granule release, and MAPK (ERK, JNK, and p38) protein, associated with both platelet granule release and TXA2 production. Lastly, arteanoflavone impedes collagen-induced platelet aggregation and blood clot formation by inhibiting fibrin production in thrombin-induced platelets. Hence, it is suggested that arteanoflavone could be valuable as an agent that effectively deters platelet inhibition and blood clot formation through antiplatelet mechanisms.

Keywords

• Arteanoflavone
• Intracellular Ca2+
• Granule secretion
• Platelet aggregation
• Cyclic nucleotide