A comparative study of antithrombotic and antiplatelet activities of different fucoidans from Laminaria japonica.

INTRODUCTION

Fucoidans extracted from brown algae represent an intriguing group of natural fucose-enriched sulfated polysaccharide, with excellent anticoagulant, antimetastatic, antiangiogenic and anti-inflammatory activities. In the present study, we compared antithrombotic activities of four fucoidan fractions with different molecular weight and sulfated ester content from Laminaria japonica in an electrical induced arterial thrombosis and their potential mechanism underlying such activity.

RESULTS AND CONCLUSIONS

In vivo middle molecular weight (MMW) fucoidan fractions with molecular weight about 28000 and 35000 exhibited better antithrombotic activity in electrical induced arterial thrombosis than low molecular weight (LMW) fucoidan LF1 and LF2 (Mw 7600 and 3900). Inhibition of arterial thrombosis occurred at dose of 0.1-0.25mg/kg for MMW fucoidans, accompanied with moderate anticoagulant activity and significant decrease of whole blood viscosity and hematocrit. The antithrombotic effects of MMW Fucoidans might be related with promotion of TFPI content and decrease of TXB2 content, without affecting platelet aggregation and 6-keto-PGF1α content in vivo. In contrast, LMW fucoidans showed a correlation among anticoagulant, antiplatelet and antithrombotic effects in vivo. Antithrombotic action of LF1 and LF2 required high dose of 2.5-10mg/kg, concomitantly with anticoagulant activity and specific inhibition of platelet aggregation in vivo. Their antithrombotic effect might be related to their promotion of TFPI and 6-keto-PGF1α, down regulation of TXB2, without affecting hemorheology. These findings suggested that fucoidan fractions with different molecular weight acted on the antithrombotic action by different mechanism. By comparison, highly sulfated fucoidan LF2 with molecular weight of 3900 seemed to be a more suitable choice of antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.