Sulfation pattern of citrus pectin and its carboxy-reduced derivatives: Influence on anticoagulant and antithrombotic effects

Citrus pectin (CP), a polysaccharide composed of [-> 4)-alpha-D-GalpA-(1 ->](n), was submitted to one or four carboxy-reduction cycles, resulting in CP-CR1 and CP-CR4, which had 40% and 2% of GalpA units, respectively. The polysaccharides were chemically sulfated and their anticoagulant and antithrombotic effects determined. Sulfated polysaccharides (CP-S, CP-CR1S and CP-CR4S) had different anticoagulant activities, doubling APTT at concentrations of 28.7, 13.2, and 4.9 mu/ml respectively. CP-CR1S and CP-CR4S also showed antithrombotic activity in vivo with ED50 of 3.01 and 1.70 mg/kg, respectively. Like heparin, they inhibited thrombin by a mechanism dependent on AT and HCII. Their hemorrhagic potential was also similar to that of heparin. According to methylation analysis, 91.1% and 50.2% of 6-O-position in CP-CR4S and CP-CR1S were sulfated, respectively. Therefore, substitution of carboxyl groups by sulfate esters in these polysaccharides increases the anticoagulant and antithrombotic effects. (C) 2012 Elsevier Ltd. All rights reserved.