Reduction of Platelet Hyperactivity by Polyphenol in An Experimental Model of Alzheimer's Disease in Rats

Background: Alzheimer's disease (AD) is increasingly associated not only with neuronal degeneration but also with platelet dysfunction, altered hemostasis, and calcium-dependent peripheral signaling abnormalities. Objective: To evaluate the effects of G-40 polyphenol on platelet aggregation, coagulation hemostasis, and intracellular calcium mobilization in a rat AD-like condition. Methods: Platelet-rich plasma and platelet suspensions obtained from control rats and rats with an AlCl3-induced AD-like condition were analyzed. Platelet aggregation was assessed by Born aggregometry after stimulation with ADP, adrenaline, and collagen. Coagulation was evaluated using thrombin time (TT), activated partial thromboplastin time (APTT/QFTV), and prothrombin time (PT, TechPlastin). Intracellular calcium was monitored in Fluo-4 AM-loaded platelets after ADP stimulation, with EGTA used as a calcium-chelating control. G-40 was tested primarily at 50 uM, with concentration-response evaluation in the 10-100 uM range for calcium readouts. Results: The AD model displayed spontaneous platelet aggregation and enhanced agonist-induced aggregation relative to controls. G-40 partially inhibited ADP- and collagen-induced aggregation in both normal and AD conditions. The AD model shortened TT, APTT, and PT, indicating a procoagulant shift, whereas G-40 markedly prolonged all three parameters. G-40 also suppressed ADP-induced intracellular Ca2+ mobilization by 40-55%, with 50 uM showing the greatest effect. Conclusions: G-40 exerts a multi-target antiplatelet and anticoagulant action in the AD-like state. Its effects are most consistently explained by attenuation of Ca2+-dependent platelet activation together with interference at common coagulation pathway steps. These findings support G-40 as a promising candidate for correcting platelet hyperreactivity and hemostatic imbalance associated with AD.

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