An arabinogalactan-glycoconjugate from Genipa americana leaves present anticoagulant, antiplatelet and antithrombotic effects

Carbohydr Polym. 2018 Dec 15:202:554-562. doi: 10.1016/j.carbpol.2018.09.003. Epub 2018 Sep 8.

Abstract

Glycoconjugates extracted from Genipa americana leaves (PE-Ga) were separated into two fractions, denominated as PFI and PFII (total carbohydrate: 23-36%/uronic acid: 9-30%; protein:4-5%; polyphenols:0.776-0.812 mg/g), mainly composed by arabinose, galactose and uronic acid and presenting high (PFI) and low (PFII) molecular weight (based on polyacrylamide electrophoresis gel and gel permeation chromatography). Uronic acid was also detected by FT-IR (wavenumbers: 1410 and 1333 cm-1) and NMR (α-GalpA). Deproteinization of glycoconjugates showed reduced protein and polyphenol levels with loss of its biological effects. PE-Ga and PFII prolonged clotting time-aPTT (3.6 and 1.8x), while PE-Ga and PFI inhibited by 48% (100 μg/μL) the ADP-induced platelet aggregation. In vivo, these glycoconjugates at 1 mg/kg inhibited (37-53%) venous thrombus formation (4.7 ± 0.1 mg) and increased bleeding time (PE-Ga and PFI:3.0x; PFII:1.7x vs. PBS:906 ± 16.7 s). In conclusion, the arabinogalactan-rich glycoconjugate of G. americana leaves, containing uronic acid, present antiplatelet, anticoagulant (intrinsic/common pathway) and antithrombotic effects, with low hemorrhagic risk.

Keywords: Chemical structure; Coagulation; Plant polysaccharides; Platelet aggregation; Thrombosis; Uronic acid.

MeSH terms

  • Animals
  • Anticoagulants / chemistry
  • Anticoagulants / isolation & purification
  • Anticoagulants / pharmacology*
  • Blood Coagulation / drug effects
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / isolation & purification
  • Fibrinolytic Agents / pharmacology*
  • Galactans / chemistry
  • Galactans / isolation & purification
  • Galactans / pharmacology*
  • Glycoconjugates / chemistry
  • Glycoconjugates / isolation & purification
  • Glycoconjugates / pharmacology*
  • Healthy Volunteers
  • Humans
  • Plant Leaves / chemistry
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / isolation & purification
  • Platelet Aggregation Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar
  • Rubiaceae / chemistry*
  • Venous Thrombosis / drug therapy

Substances

  • Anticoagulants
  • Fibrinolytic Agents
  • Galactans
  • Glycoconjugates
  • Platelet Aggregation Inhibitors
  • arabinogalactan