Diverse inhibition of plasminogen activator inhibitor type 1 by theaflavins of black tea

Abstract

Abstract. Fruits, vegetables, spices and a variety of teas are suggested for the prevention of many diseases. They encompass active, non-nutritional ingredients called nutraceuticals which are defined as food products that provide health benefits. Many nutraceuticals have been tested to identify inhibitors of plasminogen activator inhibitor (PAI-1). PAI-1 is the major and fast acting physiological inhibitor of fibrinolysis. However, preclinical studies of PAI-1 inhibitors have revealed an additional role of PAI-1 in the pathogenesis of vascular remodeling, renal injury, diabetes, obesity, Alzheimer's disease and cancer. Thus PAI-1 is a potential therapeutic target in some of these diseases. Our previous study revealed that a black tea extract (containing mostly theaflavins) inhibits PAI-1. In this study we report results for four pure (>98%) theaflavins. Inactivation of PAI-1 was tested by clot formation and by its lysis using thromboelastometry and measurements of human plasma turbidity. Among four tested theaflavins, theaflavin-3'-gallate was the most potent in PAI-1 inhibition trailed by theaflavin-3,3'-digallate, while the other two i.e., theaflavin and theaflavin-3-gallate did not show inhibitory activity.

Comparison between the clot-protecting activity of a mutant plasminogen activator inhibitor-1 with a very long half-life and 6-aminocaproic acid

“…Control samples consisted of reference and tPA-treated plasma, with tPA included to mimic clot lysis. Reference and tPA-treated plasma exhibited similar average control values, with the exception of a lower clot strength (G), maximum amplitude (MA) and rate of clot lysis after 30 min (LY 30 ) in the tPA-treated plasma due to tPA-induced clot lysis, which is consistent with previous studies (12)(13)(14)(15)(16). The MA was lower, as reference plasma lacks platelets that strengthen the blood clot (3,17-19).…”

Unusual clotting dynamics of plasma supplemented with iron(III)

“…There are no normal ranges of TEG parameters for control plasma. However, the results yielded in this study were very consistent: R (sec): 408, K (sec): 84, An (˚): 70.6, MA (mm): 27.2, LY30 (%): 0 (all parameters ±10%) (20). Observed parameters for all the controls were within these values.…”

Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? (Review)

“…Loktionov et al (50) found that tea caused a significant decrease of PAI-1 activity, but only in the subjects with an E2/E3 genotype (mean placebo 7.21 U/ml vs. mean for tea users 5.88 U/ml, P=0.007) ApoE has six common isoforms: E2/E2, E2/E3, E2/E4, E3/E3, E3/E4 and E4/E4. We have discovered that some theaflavins of black tea inhibit PAI-1 which may provide some explanation for the lower PAI-1 activity in tea lovers (27,51).…”

“…For example, the Arg369Ala substitution in active site of PAI-1 results in nonactive PAI-1 (7,8,27). Several mutants with extended half-life have been produced in the past (t ½ , 6-170 h) (8,17,20,(28)(29)(30).…”