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

Abstract

Abstract. 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 (-)-epigallocatechin-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 concentrationdependent manner with an IC 50 of 18 μM which is equal to or better than the IC 50 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.

Dual Anticoagulant/Antiplatelet Activity of Polyphenolic Grape Seeds Extract

“…In Jankun et al and Correi-da-Silva et al’s investigations estimating polyphenol anticoagulant activity, thromboelastometry was used. In the former study, inactivation of PAI-1 by tea polyphenols was presented as ineffective [22]. In contrast, the latter study used thromboelastography to show that polysulfated flavonoids featured high blood anticoagulation activity.…”

Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies

“…Two studies failed to demonstrate weight loss or reduction of markers associated to obesity upon administration of gallic acid, as reported by [121]. On the other hand, other investigations documented that administration of gallic acid reduced waist circumference, body mass index (BMI), and visceral fat in pre-obese individuals, also decreasing oxidative and inflammatory markers [128][129][130][131]. It is likely that divergent results obtained with gallic acid may depend on patient selection since more efficacy has been observed in those trials with pre-obese people.…”