Inhibition of thrombin, an unexplored function of retinoic acid.

Retinoic acid, a derivative of vitamin A, is known to possess in vivo anti-inflammatory, anti-platelet and fibrinolytic
activities. We have investigated the in vitro thrombin and platelet aggregation inhibitory activities of
vitamin A (retinol) and its derivatives, retinoic acid and retinaldehyde. The thrombin enzymatic assay was
performed fluorimetrically to assess the inhibition of thrombin (Sigma and plasma). Retinoic acid, retinaldehyde
and retinol exhibited potent inhibition of thrombin, with IC50 values of 67μg/ml, 74μg/ml and 152μg/ml, respectively
for the inhibition of thrombin (Sigma); and 49μg/ml, 74μg/ml and 178μg/ml, respectively for the
inhibition of thrombin (plasma). Amongst vitamin A and its derivatives, retinoic acid showed the highest inhibition
of both the forms of thrombin. Vitamin A and its derivatives also displayed remarkable inhibition of
platelet aggregation. This is the first report of vitamin A and its derivatives showing inhibition of thrombin and
platelet aggregation in vitro.