Structure of a homofructosan from Saussurea costus and anti-complementary activity of its sulfated derivatives.
A homogeneous water-soluble polysaccharide APS-W1, (2→1)-β-d-fructofuranosan, with an average molecular weight of 3.9kDa, 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: 2.2-18.9μg/mL; 8.3μg/mL for heparin) and alternative pathway (AP50: 11.4-115.8μg/mL; 89.2μg/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.
The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Hongwei
H
Fan
The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Fei
F
Liu
Department of Complementary Medicine, Faculty of Science and Technology, University of Westminster, London W1W 6UW, UK. Electronic address: a.bligh@westminster.ac.uk.
S W Annie
SW
Bligh
The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Songshan
S
Shi
The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: shunchunwang@126.com.
Shunchun
S
Wang
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots; D011134:Polysaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011817:Rabbits; D030441:Saussurea; D012756:Sheep; D013431:Sulfates / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
D010936:Plant Extracts; D011134:Polysaccharides; D013431:Sulfates
Anti-complement; Homofructosan; Polysaccharide; Saussurea costus; Sulfated derivatives