Structure of a homofructosan from Saussurea costus and anti-complementary activity of its sulfated derivatives

Abstract

A homogeneous water-soluble polysaccharide APS-W1, (2 → 1)-β-d-fructofuranosan, with an average molecular weight of 3.9 kDa, was isolated and characterized from the roots of <i>Saussurea costus</i>. Five sulfated derivatives of APS-W1 with different degrees of sulfation were prepared and they showed strong inhibitory effect on the complement activation through the classical pathway (CP₅₀: 2.2–18.9 μg/mL; 8.3 μg/mL for heparin) and alternative pathway (AP₅₀: 11.4–115.8 μg/mL; 89.2 μg/mL for heparin). Mechanism studies by using complement-depleted sera indicated that sulfated derivatives with different positions of sulfation targeted to different complement proteins. Meanwhile the sulfated derivatives have limited anticoagulant effect based on re-calcification time and thrombin time. These results suggested that the sulfated derivatives prepared from APS-W1 could be promising potential complement inhibitors for the treatment of diseases caused by an over-activated complement system.