Giuseppe Guglielmini, Emanuela Berardi, Federica Messina, Maria Carla Marcotullio, Paolo Gresele
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引用次数: 0
Abstract
Background: Resveratrol is a polyphenol of red wine that is thought to contribute to the "French paradox" by protecting against atherosclerotic cardiovascular events. It has anti-inflammatory and antioxidant properties and enhances nitric oxide (NO) production. However, in conditions of severe endothelial dysfunction, its cardiovascular protective effects may be limited. Our study aimed to synthesize and characterize a new nitro derivative of resveratrol, trinitroresveratrol (TN-RSV), for its potential nitric oxide-donating and antiplatelet effects.
Methods: 3,5,4'-tri-[4-(nitrooxy)butanoyl]oxy resveratrol (TN-RSV) was synthetized starting from commercial resveratrol (RSV) through the intermediacy of 3,5,4'-tri-(4-bromo-butanoyl)oxy resveratrol. Platelet aggregation was assessed by light transmission aggregometry (LTA) using collagen as agonist. The release of nitric oxide (NO) from TN-RSV or from activated platelets was assessed as the concentration of the NO degradation products (nitrites plus nitrates, NOx) in the supernatant. Platelet adhesion to collagen under flow conditions was assessed using a parallel plate perfusion chamber. Reactive oxygen species (ROS) production from collagen-activated platelets was assessed by flow cytometry using the fluorescent probe H2DCFDA.
Results: TN-RSV spontaneously released NO and significantly inhibited collagen-induced platelet aggregation in a dose-dependent manner. This effect was greater than that of resveratrol and it was not affected by the preincubation with L-NAME, a nitric-oxide synthase (NOS) inhibitor, indicating that TN-RSV directly inhibits platelet activation independently of NOS.
Conclusions: Our findings suggest that TN-RSV has potential as an antiplatelet agent and that further research exploring its therapeutic applications for conditions associated with endothelial dysfunction and platelet hyperreactivity is warranted.
期刊介绍：
Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures.
Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology.
Studies of plant extracts are not suitable for Pharmacological Reports.
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