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Theaflavin digallate inactivates plasminogen activator inhibitor: Could tea help in Alzheimer's disease and obesity?

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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 ┬ÁM 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.
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Document Type: Research Article

Affiliations: Urology Research Center, Department of Urology, University of Toledo - Health Science Campus, Toledo, OH 43614, USA

Publication date: July 1, 2010

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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