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

• A (2 → 1)-β-d-fructofuranosan (APS-W1) was isolated from Saussurea costus.
• Sulfated APS-W1 compounds gave strong anti-complement and low anticoagulant effects.
• The higher the degree of sulfation of APS-W1 gave the better anti-complement effect.
• The positions of sulfate groups govern the targets of the complement proteins.

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 Saussurea costus. 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.