Polyphenolic-polysaccharide conjugates of Sanguisorba officinalis L. with anticoagulant activity mediated mainly by heparin cofactor II.
A macromolecular complex has been isolated from the dried flowering parts of medicinal plant Sanguisorba officinalis L. (So) by multi-step extraction procedure, including that with extraction by organic solvents to degrease the plant material, then with hot alkali, followed by neutralization, partitioning with organic solvents and dialysis. The complex was purified by size-exclusion chromatography into five fractions labeled as So1-So5. Individual fractions differed in the chemical composition and molecular weight distribution patterns. In vitro anticoagulant activity tests showed in all fractions more or less important inhibition of plasma clots, however, So3 and So4 were the most active. The anticoagulant activity of So3 was even more significant than that of the unfractionated complex So. These S. officinalis conjugates were able to inhibit mainly the activity of thrombin when they were mediated by heparin cofactor II, but what was unexpected they were the non-direct inhibitors of factor Xa, mediated by antitrombin, where such mechanism of action is typical for a highly sulphated glycosaminoglycans.
Departament of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 29, 50-370, Wrocław, Poland. Electronic address: izabela.pawlaczyk@pwr.wroc.pl.
Izabela
I
Pawlaczyk-Graja
Departament of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 29, 50-370, Wrocław, Poland.
Sebastian
S
Balicki
Departament of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 29, 50-370, Wrocław, Poland.
Rafał
R
Ziewiecki
Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dubravská cesta 9, 845 38 Bratislava, Slovakia.
Mária
M
Matulová
Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dubravská cesta 9, 845 38 Bratislava, Slovakia.
Peter
P
Capek
Departament of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 29, 50-370, Wrocław, Poland; WroVasc-Integrated Cardiovascular Center, Regional Specialist Hospital in Wroclaw, Research and Development Center, Kamienskiego 73a, 51-124, Wroclaw, Poland.
Roman
R
Gancarz
D000925:Anticoagulants / Q000302:isolation & purification / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D035264:Flowers / Q000737:chemistry; D015844:Heparin Cofactor II / Q000502:physiology*; D006801:Humans; D010314:Partial Thromboplastin Time; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D059808:Polyphenols / Q000302:isolation & purification / Q000494:pharmacology*; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D011517:Prothrombin Time; D031993:Sanguisorba / Q000737:chemistry
D000925:Anticoagulants; D010936:Plant Extracts; D059808:Polyphenols; D011134:Polysaccharides; D015844:Heparin Cofactor II
Anticoagulant activity; Heparin cofactor II; NMR; Plant glycoconjugate; Sanguisorba officinalis