Proteolysis in general and particularly the
serine proteases are causally involved in many physiological processes and different diseases. Recently it was reported that
plasminogen activator inhibitor type one (PAI-1) inactivation can alleviate the symptoms of
Alzheimer's disease and reduce the
body weight of obese individuals. In our broad search for natural compounds and their derivatives that can inhibit
PAI-1, we include the
polyphenols of teas since
teas (green and black) or their components have been reported to alleviate the symptoms of both
obesity and
Alzheimer's disease. Inactivation of
PAI-1 was measured in human plasma using thromboelastography. We used known
PAI-1 inhibitor PAI039 [{1-benzyl-5-[4-(trifluoromethoxy) phenyl]-1H-indol-3-yl}(oxo)
acetic acid] as a positive control and (-)-epigallo-catechin-3-gallate (EGCG), its
prodrug octaacetate EGCG (OcAc EGCG) and
theaflavin digallate [TH(2)] as potential
PAI-1 inhibitors. We found that inactivation of
PAI-1 in plasma by EGCG and OcAc EGCG was low or very low. However, TH(2) inactivated
PAI-1 in a concentration-dependent manner with an IC50 of 18 microM which is equal to or better than the IC50 reported for known
PAI-1 inhibitor PAI039. Clearly TH(2) inhibits
PAI-1 and might play a role in slowing down the progression of
Alzheimer's disease or
obesity by a PAI-1-dependent pathway. While the clinical value of TH(2) has not been proven, long-term prospective studies assessing its efficacy are warranted due to the benign nature of the substance.