Tea Inhibits Hageman Factor

Abstract

Plasma prekallikrein (PK)activation exerts both physiological and pathological effects within the cardiovascular system and CNS. Activated PK (kallikrein) controls cytokine release from human mononuclear cells, and controls both the intrinsic blood coagulation and the alternative complement cascades. The uncontrolled activation of these cascades results in the development of pathological pain and angioedema. PK is involved with the repair processes that replace injured/damaged tissue. Under pathological conditions, the activation of PK is triggered to be excessively robust. Kallikrein levels are indicated to be associated with hereditary angioedema and myocardial infarction, whereby kallikrein amplifies the generation of activated factor XII (FXIIa) and bradykinin (BK). We hypothesized that kallikrein inhibitors represent a novel class of drugs for curbing inflammation with a broad spectrum of activity. We sought to test the anti‐inflammatory effects of medicinal plants, known for their anti‐inflammatory properties in a system of BK‐forming capacity in endothelial cells and amidolytic kallikrein/FXIIa assay method. The water extracts of tea (Camellia sinensis) inhibited kallikrein and FXIIa with IC50s of 200 and 27 mg/mL. 50mg/mL crude water extracts did not influence cell viability. The extracts inhibited FXIIa ‐induced cell migration. Bioassay guided fractionation was performed on the water extracts to isolate the active compounds. Known polyphenols were ineffective in inhibiting kallikrein and FXIIa. The purified fraction displayed FXIIa inhibition of 88 ±1.5% at a concentration of 700 mg/mL. The bioactive composition comprising the aqueous extract and active fraction of tea may be used for the purpose of reducing FXIIa‐dependent inflammation and thrombosis.