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

• Published in: Journal of natural products (Washington, D.C.) Vol. 61; no. 11; pp. 1356 - 1360
• Main Authors: Dong, H, Chen, S.X, Kini, R.M, Xu, H.X
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.11.1998; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Animals; anticoagulants; Anticoagulants - chemistry; Anticoagulants - isolation & purification; Anticoagulants - pharmacology; Biological and medical sciences; Blood Coagulation - drug effects; blood coagulation factors; catalytic activity; Cattle; chemical constituents of plants; chemical structure; Chemistry, Medicinal; Factor Xa Inhibitors; General pharmacology; Geum; Humans; Hydrolyzable Tannins - chemistry; Hydrolyzable Tannins - isolation & purification; Hydrolyzable Tannins - pharmacology; In Vitro Techniques; Kinetics; Life Sciences & Biomedicine; Medical sciences; medicinal plants; Partial Thromboplastin Time; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Sciences; Plants, Medicinal - chemistry; Prothrombin Time; Rabbits; Science & Technology; spectral analysis; tannins; Tannins - chemistry; Tannins - isolation & purification; Tannins - pharmacology; thrombin; Thrombin - antagonists & inhibitors; Thrombin Time; China; Asia; Japan; Blood coagulation; Rosaceae; Rabbit; Coagulation Factor Xa; Thrombin; Anticoagulant; Medicinal plant; Tannin; Folk medicine; Structure activity relation; Dicotyledones; Angiospermae; Ungulata; Human; Serine endopeptidases; Aldose; Bovine; Enzyme; Pharmacognosy; Whole plant; Benzene derivatives; Enzyme inhibitor; Lagomorpha; In vitro; Peptidases; Vertebrata; Mammalia; Biphenyl derivatives; Animal; Plant origin; Hydrolases; Spermatophyta; Artiodactyla
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np9801458

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-di-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 mu M, 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.