Anticoagulant and antithrombotic effects of chemically sulfated guar gum.

Heparin is an extremely important and recognized anticoagulant and antithrombotic agent. Obtained from animal sources and being highly potent, risks of contamination by pathogens and bleeding are some concerns related to heparin use. In the search for alternatives to heparin, several researches have been performed with chemically sulfated polysaccharides obtained from non-animal sources. In this work, studies with guar gum led to a partially hydrolyzed and chemically sulfated derivative (hGGSL) with Mw of 15.6 kDa, DS of 1.91 and promising anticoagulant and antithrombotic properties. In vitro, hGGSL was only 4.5× less potent than unfractionated heparin, acting mainly by inhibiting thrombin via antithrombin, and had its anticoagulant activity inhibited by protamine. In vivo, hGGSL showed potential for subcutaneous use and was effective in reducing venous thrombosis. Collectively, the results provide a basis for the development of a new anticoagulant and antithrombotic agent.

Anticoagulant activity of native and partially degraded glycoglucuronomannan after chemical sulfation.

Heparin has great clinical importance as anticoagulant and antithrombotic agent. However, because of its risks of causing bleeding and contamination by animal pathogens, several studies aim to obtain alternatives to heparin. In the search for anticoagulant and antithrombotic agents from a non-animal source, a glycoglucuronomannan from the gum exudate of the plant Vochysia thyrsoidea was partially hydrolyzed, and both native and partially degraded polysaccharides were chemically sulfated, yielding VThS and Ph-VThS respectively. Methylation analysis indicated that sulfation occurred preferentially at the O-5 position of arabinose units in the VThS and at the O-6 position of mannose units in Ph-VThS. In vitro aPTT assay showed that VThS and Ph-VThS have anticoagulant activity, which could be controlled by protamine, and ex vivo aPTT assay demonstrated that Ph-VThS is absorbed by subcutaneous route. Like heparin, they were able to inhibit α-thrombin and factor Xa by a serpin-dependent mechanism. In vivo, VThS and Ph-VThS reduced thrombus formation by approximately 50% at a dose of 40 IU/kg, similarly to heparin. The results demonstrated that the chemically sulfated polysaccharides are promising anticoagulant and antithrombotic agents.