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Terminalia methanol extracts inhibit the amidolytic activity of human activated factor XII (Hageman factor)

The long‐term goal of this study is to develop the selective inhibitors of FXIIa based on traditional medicine, which might be safe, and effective. There are positive correlations between increased plasma FXIIa levels with coronary heart disease as well as increased risk of recurrent coronary events. Although they maintain a normal hemostasis, FXII knockout mice (FXII−/−) display defective arterial thrombus formation. In addition, FXII−/− mice are protected from development of cerebral ischemia and pulmonary embolism. Thus, inhibition of FXIIa would help prevent cardiovascular diseases. The present study examines the effects of different but related herbal medicines that impact on the plasma blood coagulation FXII. While it initiates the activation of blood coagulation to stop any bleeding, FXII helps the remaining blood clotting factors and platelets to keep certain circulating pathogenic microorganism close to the phagocytes. The negative charge on the microorganism surface or platelet polyphosphate (poly P) binds readily to zymogen FXII, resulting in the activation of FXII. Evidence indicates that poly P containing pathogens promote FXII‐mediated blood coagulation independent of factor XI, reflecting a novel poly P‐induced thrombus formation. The methanol extracts of T. chebula fruit, T. bellirica fruit, T. arjuna fruit, and T. arjuna bark blocked FXIIa activity with IC50 values of 30, 50, 190, 190 and 27 mg/ml, respectively. Two isolated compounds from Terminalia, Arjunoglucoside II and arjunic acid blocked FXIIa activity with IC50 values of 370 and 780 μM, respectively. T. chebula fruit, T. and arjuna fruit extracts at 50 mg/ml did not affect endothelial cells viability. Overall, T. chebula fruit and T. arjuna fruit extracts might be useful to improve symptoms of FXIIa‐dependent inflammation and thrombosis.