The inhibition of elements of the plasminogen activator system [urokinase (uPA), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1)] plays an important role in human diseases. PAI-1 is overexpressed in obesity and diabetes, and the inhibition of this protein has been postulated to alleviate the symptoms of both disorders. We found that two theaflavins (TFs) from black tea inhibit PAI-1 and we suggest that the beneficial effects of drinking tea may be associated with the suppression of PAI-1 activity by theaflavins. Epidemiological studies are controversial; some studies show the beneficial effects of drinking black tea on obesity and diabetes, while others do not. TFs, a family of compounds that can comprise up to 40% the dry weight of black tea, are responsible for the characteristic color, and they are known to chelate metals. We hypothesized that the content/variety of metals present in drinking water may be one of the reasons for such controversies in the population studies. TFs are excellent chelating compounds by trapping metals into complexes; thus, the quality of water used for tea preparation may influence changes in the formation of new products according to TF affinity for different metals, as well as their high molecular weight oxidation products. Our modeling and docking studies suggest that TF/metal complexes have similar affinity to PAI-1 as native TFs. However, analyses using liquid chromatography-mass spectroscopy (LC-MS) revealed the presence of TF degradation products in tea brewed using water containing metal salts. These can further form high molecular weight oxidation products. Thus, metals present in tea could diminish the beneficial effects of black tea by reducing TF concentration via metal-induced degradation and precipitation.

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