Evaluation of the antiaggregant activity of ascorbyl phenolic esters with antioxidant properties

Abstract

Beneficial effects of the antioxidant L-ascorbic acid (Asc) in human health are well known. Its particular role in hemostasis deserves further consideration, since it has been described a dose-dependent effect of Asc in platelet activity. Contrary, it has been demonstrated that phenolic compounds have inhibitory effects on platelet aggregation stimulated by the physiological agonist thrombin (Thr). Here, we have evaluated the actions of three synthetic phenolic esters of Asc: L-ascorbyl 6-protocatechuate (Prot Asc), L-ascorbyl 6-gallate (Gal Asc), and L-ascorbyl 6-caffeate (Caf Asc). All these Asc derivatives exhibited greater radical scavenging activity than Asc, and in experiments using human platelets from healthy subjects, they do not evoke changes in platelet viability upon their administration. Nevertheless, these compounds altered platelet calcium homeostasis in response to Thr, although Prot Asc induced a smaller effect than Gal Asc, Caf Asc, and Asc. As a consequence, platelet aggregation was also impaired by these compounds, reporting Prot Asc and Caf Asc a weaker antiaggregant action than Gal Asc and Asc. Treatments with Gal Asc and Caf Asc altered in larger extent the phosphorylation pattern of pp60(Src) and mammalian target of rapamycin (mTOR) evoked by stimulating human platelets with Thr. Summarizing, Prot Asc is the ascorbyl phenolic ester with the strongest antioxidant properties and weakest antiaggregant actions, and its use as antioxidant may be safer than the rest of derivatives in order to prevent thrombotic alteration in patients that need treatment with antioxidant therapies.

Antithrombotic Effect of Oil from the Pulp of Bocaiúva—Acrocomia aculeata (Jacq.) Lodd. ex Mart. (Arecaceae)

“…The results were expressed as the mean percentage of platelet viability. All experiments were performed in triplicate, not exceeding 3 h after collection [19].…”

Therapeutic Perspective of Vitamin C and Its Derivatives

“…In order to synthesize ASA derivatives that maintain the antioxidant properties of ASA with decreased side effects on platelet function compared to ASA, and keeping in mind the inhibitory effect of some phenolic compounds on platelet aggregation stimulated by thrombin, new ASA phenolic esters— l -ascorbyl-6-protocatechuate (6-Prot-ASA, 12 ), l -ascorbyl-6-gallate (6-Gal-ASA, 13 ) and l -ascorbyl-6-caffeate (6-Caf-ASA, 14 )—were synthesized by Lopez et al (Figure 6) [75].…”

The Antioxidant and Antiproliferative Activities of 1,2,3-Triazolyl-L-Ascorbic Acid Derivatives

“…Due to the low one electron reduction potential of the ascorbate radical (RA)/ascorbate (A) couple (Figure 2), almost every oxidizing radical formed in the biological system, including the hydroxyl (HO • ), alkoxyl, peroxyl, thiol, and tocopheroxyl radicals cause one-electron oxidation of the ascorbate anion, resulting in the formation of the resonance stabilized ascorbate radical which can be recycled back to ascorbate [15,16]. Furthermore, structural modifications of hydroxyl groups of L-ASA by the introduction of lipophilic moieties have led to L-ASA derivatives with improved radical scavenging ability compared to L-ASA, especially in lipophilic parts of biological system [17,18,19,20,21,22]. While L-ASA has an antioxidant property and protects the cell from damage caused by free radicals, when used in pharmacological (millimolar) concentrations achieved through intravenous administration L-ASA shows pro-oxidant activity [13,23,24,25].…”