Tannins as Hemostasis Modulators

Abstract

The hemostasis system is often affected by complications associated with cardiovascular diseases, which results in thromboembolic events. Compounds of plant origin and plant extracts are considered as a promising source of substances that could modulate the functioning of the hemostasis system and thus reduce the risk of thromboembolism. Among them, tannins, which are plant-origin compounds with potential effects in hemostasis, deserve a special mention. This paper describes the hemostasis-modifying ability of three groups of tannins, namely ellagitannins, gallotannins, and procyanidins. The review highlights the desirable as well as undesirable influence of tannins on specific components of hemostasis, namely platelets, coagulation system, fibrinolysis system, and endothelium, and the multidirectional effect of these compounds on the thrombotic process. Studies performed under normal and pathological conditions such as diabetes or hypercoagulation are described, and the pathophysiology-dependent action of tannins is also highlighted. Most of the studies presented in the paper were performed in vitro, and due to the low bioavailability of tannins more studies should be conducted in the future to understand their actual activity in vivo.

Keywords: coagulation; endothelium; platelets; tannins; thrombosis.

FIGURE 1

Possible effects of ellagitannins metabolism and resulted dual activity towards hemostasis (Bock et al., 1981; Spigoni et al., 2016).

FIGURE 2

Main effects of tannins on hemostasis. “→” indicates activatory pathways and “˧” indicates inhibitory pathways that occur during hemostasis regulation. “+” and “–” indicate activatory and inhibitory effect of tannins on these pathways, respectively. Green color indicates favorable and red color indicates the unfavorable effect of tannins. Firstly, the picture shows the effect of tannins on particular signaling pathways in platelet which eventually also affect their shape change, PS translocation, secretion, and aggregation. Furthermore, the effect of tannins on coagulation factors and fibrin formation is shown. The influence of tannins on fibrinolysis and components that regulate this process is presented. The picture shows also tannins effect on endothelial NO and PGI₂ synthesis as well as ICAM-1 and VCAM-1 expression. Numbers in circles represent specific compounds, fractions or extracts. Dotted lines indicate the processes affected by tannins. (1) PGG, (2) parameritannin A1, (3) aesculitannin B1, (4) oligomeric B-type procyanidins, (5) O-trigalloyl-beta-D-glucose, (6) isocorilagin, (7) pomegranate extract, (8) cinnamtannin 1B, (9) water–methanolic procyanidin fraction of the water–methanolic extract obtained from Medemia argun nuts, (10) cocoa procyanidins, (11) water-methanolic Potentilla erecta rhizome extract, (12) rugosin E, (13) pedunculagin, (14) tellimagrandin II, (15) casuariin, (16) 5-desgalloylstachyurin, (17) procyanidin fraction of an aqueous extract of Brownea grandiceps Jacq., (18) procyanidin B2, (19) hamamelitannin, (20) walnuts, (21) corilagin, (22) procyanidin-rich chocolate, (23) procyanidin fractions from grape pomace, (24) grape seeds procyanidin, (25) procyanidin fraction of a water–ethanolic extract from Croton celtidifolius, (26) 2,3-cis procyanidins (isolated from the ethyl acetate fraction of a methanolic extract from Nelia meyeri leaves (27) 2,3-trans procyanidins (isolated from the ethyl acetate fraction of a methanolic extract from Salix spp. Bark, (28) procyanidin C1 (29) procyanidin fraction of an acetone–water extract obtained from Ribes nigrum, (30) polyphenol fractions of acetone–water extracts obtained from Rubus caesius and Rubus idaeus.