Effects of tannins from Geum japonicum on the catalytic activity of thrombin and factor Xa of blood coagulation cascade

J Nat Prod. 1998 Nov;61(11):1356-60. doi: 10.1021/np9801458.

Abstract

Bioassay-guided fractionation of the MeOH extract of the whole plant of Geum japonicum led to the isolation of seven known tannins. They were identified by spectroscopic methods as penta-O-galloyl-beta-glucoside (1), pedunculagin (2), 2, 3-(S)-hexahydroxydiphenoyl-D-glucose (3), tellimagrandin II (4), 2, 6-di-O-galloyl-D-glucose (5), casuariin (6), and 5-desgalloylstachyurin (7). Compounds 1, 2, 4, 6, and 7 showed potent anticoagulant activity by significantly prolonging the clotting of rabbit plasma. The inhibitory effect of 2 was competitively directed against thrombin. Its IC50 values for inhibition of the enzymatic activity of thrombin on synthetic substrate and fibrinogen were 0.18 and 0.15 microM, respectively. On the other hand, compounds 1, 4, 6, and 7 are mixed noncompetitive inhibitors of thrombin. Their IC50 values for inhibition of fibrinogen hydrolysis were twofold to sevenfold lower than those for the inhibition of synthetic substrate hydrolysis. Factor Xa was competitively inhibited by compounds 1, 2, 4, 6, and 7. The phenolic hydroxyl groups of the active tannins appear to play an important role in their inhibitory effect on the enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / chemistry
  • Anticoagulants / isolation & purification
  • Anticoagulants / pharmacology*
  • Blood Coagulation / drug effects*
  • Cattle
  • Factor Xa Inhibitors*
  • Humans
  • Hydrolyzable Tannins / chemistry
  • Hydrolyzable Tannins / isolation & purification
  • Hydrolyzable Tannins / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Partial Thromboplastin Time
  • Plants, Medicinal / chemistry*
  • Prothrombin Time
  • Rabbits
  • Tannins / chemistry
  • Tannins / isolation & purification
  • Tannins / pharmacology*
  • Thrombin / antagonists & inhibitors*
  • Thrombin Time

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Hydrolyzable Tannins
  • Tannins
  • casuariin
  • Thrombin