ABSTRACT
Proanthocyanidins, such as cinnamtannin B-1, are polyphenolic compounds with antioxidant activity that induce apoptosis in a number of tumoral cells. We have now investigated the pro- or anti-apoptotic effects of cinnamtannin B-1 in human platelets. Platelet stimulation with thrombin induced cellular apoptosis, as detected by phosphatidylserine exposure and the activation of caspases-3 and -9. Pretreatment for 30 min with cinnamtannin B-1 impaired thrombin-induced apoptosis in platelets. Thrombin has been shown to induce H(2)O(2) generation in platelets, which induced similar apoptotic events than thrombin in these cells. Pretreatment with cinnamtannin B-1 reduced H(2)O(2)-induced phosphatidylserine exposure and caspase activation. Finally, platelet stimulation with thrombin induced translocation of caspases-3 and -9 to the cytoskeletal (Triton-insoluble) fraction, which is important for their activation and the development of apoptotic events. Pretreatment with cinnamtannin B-1 impaired translocation of caspases-3 and -9 to the cytoskeleton and, as a result, procaspases are accumulated in the Triton-soluble fraction. Our results provide evidence for the antiapoptotic actions of cinnamtannin B-1 in human platelets.
Subject(s)
Anthocyanins/pharmacology , Apoptosis/drug effects , Blood Platelets/drug effects , Laurus/chemistry , Anthocyanins/chemistry , Blood Platelets/physiology , Caspase 3/metabolism , Caspase 9/metabolism , Cell Fractionation , Enzyme Activation , Humans , Hydrogen Peroxide/pharmacology , Molecular Structure , Oxidants/pharmacology , Phosphatidylserines/metabolism , Plant Extracts/chemistry , Proanthocyanidins , Thrombin/pharmacologyABSTRACT
Type 2 diabetes mellitus induces a number of cardiovascular disorders, including platelet hyperactivity and hyperaggregability, which is associated to an increased oxidant production and abnormal cytosolic Ca2+ mobilization. In the present study, we have investigated the effect of cinnamtannin B-1 obtained from bay wood on oxidants production, Ca2+ mobilization and aggregation in platelets from type 2 diabetic donors. Pretreatment of platelets with cinnamtannin B-1 reversed the enhanced oxidants production and Ca2+ mobilization, including Ca2+ entry, evoked by thapsigargin plus ionomycin or thrombin, observed in platelets from diabetic subjects, so that in the presence of cinnamtannin B-1 Ca2+ entry was similar in platelets from healthy and diabetic subjects. In addition, cinnamtannin B-1 reduced thrombin-induced aggregation in platelets from type 2 diabetic subjects. We conclude that cinnamtannin B-1 exerts an effective antioxidant action in platelets from patients with type 2 diabetes mellitus and reverses the enhanced Ca2+ mobilization and hyperaggregability.
