Preventive effects of guava (Psidium guajava L.) leaves and its active compounds against α-dicarbonyl compounds-induced blood coagulation

Diabetes is associated with a hypercoagulable state which may accelerate atherosclerosis, thrombosis and the diabetic microvascular complication. Endogenously produced α-dicarbonyl compounds are linked to the pathophysiology of diabetic complications. The effects of α-dicarbonyl compounds on coagulation parameters in vitro and the anticoagulant activities of aqueous extracts from guava leaves were examined. Incubation of plasma with glyoxal or methylglyoxal at 0.1 mM showed a significant decrease in thrombin clotting time (TT) (P < 0.05). However, they exhibited slight prolongation of the prothrombin time (PT) at 0.5 mM and no effect on the activated partial thromboplastin time (APTT). In order to define the action mechanism of the hypercoagulant activity, coagulation factors such as fibrinogen and antithrombin III activity were evaluated. The fibrinogen contents in plasma were decreased slightly with increasing concentrations of glyoxal and methylglyoxal. Moreover, methylglyoxal inhibited antithrombin III activity and over 80% of the activity was lost at 1.2 mM methylglyoxal. In contrast, guava leaf extracts exhibited significant inhibition of TT shortening induced by methylglyoxal. Guava leaf extracts and its active phenolic compounds including ferulic acid, gallic acid and quercetin also displayed a protective effect against methylglyoxal-induced loss of activity of antithrombin III. Thus, guava leaf extracts are a potent antiglycative agent and anticoagulant, which can be of great value in the preventive glycation-associated cardiovascular diseases in diabetes.