Algal fucoidan, unlike heparin, has thrombolytic activity in a murine arterial thrombosis model

Abstract

Thrombolytic effects of fucoidans were investigated in the FeCl3-induced arterial thrombus mouse model and compared with heparin and tissue plasminogen activator (t-PA). Thrombosis model was made by applying 5% FeCl3 on the carotid artery of a Balb/c mouse. Twenty minutes after complete occlusion, a couple of test agents including fucoidan were infused into each mouse group with various doses intravenously, before measuring the time to reperfusion. The occluded arteries were reperfused 37.5 ± 12.4 min after administration of unfractionated fucoidan from Undaria pinnatifida sporophylls (UPS-UF) with a dose of 100 mg/kg. In the mice given either a low-molecular-weight UPS fucoidan or fucoidan source from Fucus vesiculosus (FV-UF), reperfusion was delayed at 55.0 ± 8.0 min with a higher reperfusion effective dose (RED) of 1 g/kg or at 63.3 ± 7.2 at RED of 200 mg/kg, respectively. In the control mice given t-PA of 15 mg/kg, reperfusion occurred at 24.8 ± 6.5 min after administration. In contrast, reperfusion was not observed in the occluded mice given heparin (P < 0.001) in the range of 60-1000 mg/kg. Minimal injection of fucoidan in addition to a given t-PA-enabled restoration of blood flow in the blocked artery without reocclusion at 17.2 ± 2.3 min postinjection (P < 0.002). In conclusion, algal fucoidan has both thrombolytic activity and a stimulatory effect on the thrombolytic activity of t-PA in a dose-dependent manner at an arterial thrombosis model.

Fucoidan Prevents the Progression of Osteoarthritis in Rats

“…21 Fucoidan is a commonly known high-molecular weight polysaccharide (200-500 kDa). In our study, we utilized the low-molecular weight (30-50 kDa) fucoidan from Hizikia (Fig.…”

Stimulatory effect of an algal fucoidan on the release of vascular endothelial tissue-type plasminogen activator as a mechanism of fucoidan-mediated thrombolysis

“…Therefore, either removing inhibitory pathway or increasing the t-PA production directly may lead to an enhancement of thrombolysis. An algal fucoidan with a branch structure has been shown to bind to either thrombin [9] or PAI-1 [10], and demonstrated both thrombolytic and stimulatory effects in a mouse model of arterial thrombosis as reported previously [11]. Fucoidan-dependent polymorphonuclear neutrophil accumulation on the endothelial layer may promote thrombolysis by either activating t-PA release from the endothelial layer or releasing nonplasmin protease directly from polymorphonuclear neutrophils.…”

“…The increased plasma levels of active t-PA in the Undaria-fucoidan infusion group suggest that t-PA release was stimulated after the injection of fucoidan, leading to either fucoidan-mediated thrombolysis or a synergistic stimulatory effect observed in the presence of an ineffective amount of t-PA in a mouse arterial thrombus model [11]. Bradykinin, the most potent known stimulator of t-PA in humans, is an inflammatory vasodilator peptide that acts primarily through the neurokinin 2 Blood Coagulation and Fibrinolysis 2016, Vol 00 No 00 type 1 receptor and mediates neurogenic inflammation similar to other stimulants that trigger the sympathetic nervous system.…”

“…Unfractionated fucoidan from Undaria pinnatifida sporophylls was prepared as previously described [11]. A commercial source of fucoidan from Fucus vesiculous was purchased from Sigma (St. Louis, Missouri, USA) and used after further purification through successive hydrophobic gel chromatography.…”

In vitro thrombolytic and cytotoxic evaluation of Mentha arvensis L., Mentha spicata L. and Mentha viridis L

“…Atherothrombotic diseases or coronary artery thrombosis are common disorders in the world.Now a daysatherothrombotic diseases aretreatedby streptokinase(SK), urokinase(UK) or tissue plasminogen activators (t-PA) which are also used as a clinical thrombolytic agent for the treatment of severe or myocardial infarction,massive deep venous thrombosis, pulmonary embolism and occluded intravenous or dialysis cannulas [1]. Streptokinase (SK) and urokinase(UK) are widely used in Bangladesh and other developing countries because of their availability and lower cost [2] as compared to other thrombolytic drugs.…”