Astaxanthin suppresses thrombosis by inhibiting both platelet activation and blood coagulation

Thrombosis, the leading cause of death worldwide, involves both platelet activation and coagulation reaction. Astaxanthin (ASX) is a carotenoid with potent antioxidant activity and beneficial effects to the cardiovascular system. This study aims to systematically elucidate the antithrombotic potential of ASX and the underlying mechanisms.

Rats and mice were treated with ASX by gavage to examine the in vivo effects of ASX. Human platelets and liver cells were directly treated with ASX to evaluate its in vitro effects. Network pharmacology and immunoblotting were performed to analyse the targets of ASX. Thrombus components including platelets and fibrin were visualized by specific fluorescent antibodies using intravital microscopy.

ASX treatment led to attenuated platelet aggregation, adhesion, spreading, clot retraction and reduced integrin activation and granule secretion. ASX inhibited reactive oxygen species (ROS) production, and its downstream signalling pathways PI3K/Akt/mTOR and MAPK/ERK during platelet activation. ASX suppressed blood coagulation, both extrinsic and intrinsic, by interfering with hepatic transcription of coagulation factors through reducing hepatic ROS and ROS-responsive hepatocyte nuclear factor 4α (HNF4α). Treatment with ASX in human platelets and liver cells recapitulated the observations in animals. ASX and aspirin comparably inhibited FeCl₃-induced arterial thrombosis and stenosis-induced venous thrombosis. However, unlike aspirin which targets only platelets, ASX inhibited both platelets and fibrin in the cremaster thrombosis model without causing excessive bleeding.

ASX exhibits multiple antithrombotic effects by suppressing platelet- and hepatic-ROS and the downstream responsive pathways. ASX represents a novel strategy for thrombosis prevention.