Evaluación de las interacciones de metabolitos polifenólicos obtenidos de Solanum tuberosum sobre la actividad antiagregante plaquetario del ácido acetil salicílico

Abstract

La combinación de terapias es una estrategia efectiva en el ámbito clínico, ya que mejora la respuesta farmacológica y reduce el riesgo de efectos secundarios. Se investigó el efecto antiagregante de los polifenoles ácido cafeico (AC) y ácido clorogénico (ACG) de Solanum tuberosum, junto con ácido acetilsalicílico (ASA), en plasma rico en plaquetas. Los resultados mostraron efectos dependientes de la concentración de AC y ACG, así como de ASA. Se observó una interacción sinérgica con AC y una disminución en la efectividad antiagregante con ACG. Se necesitan estudios adicionales para determinar las concentraciones óptimas y posibles efectos sinérgicos de estos compuestos combinados con ASA. La combinación de terapias es una estrategia efectiva en el ámbito clínico, ya que mejora la respuesta farmacológica y reduce el riesgo de efectos secundarios. Se investigó el efecto antiagregante de los polifenoles ácido cafeico (AC) y ácido clorogénico (ACG) de Solanum tuberosum, junto con ácido acetilsalicílico (ASA), en plasma rico en plaquetas. Los resultados mostraron efectos dependientes de la concentración de AC y ACG, así como de ASA. Se observó una interacción sinérgica con AC y una disminución en la efectividad antiagregante con ACG. Se necesitan estudios adicionales para determinar las concentraciones óptimas y posibles efectos sinérgicos de estos compuestos combinados con ASA. (Texto tomado de la fuente)

Combination therapy is a therapeutic strategy that can be highly effective in the clinical setting, since drugs used in association can improve the pharmacological response and, at the same time, make it possible to reduce doses and the risk of possible side effects (Yang et al., 2014). Considering this approach, it is appropriate to investigate or explore new therapeutic options that contribute to decrease the impact of thrombotic diseases on public health. Therapies based on natural sources could offer active metabolites that, when interacting synergistically, provide new possibilities for combination therapies at the pharmacological level. In this study, the antiaggregation effect of the polyphenols previously identified in Solanum tuberosum, caffeic acid and chlorogenic acid, in the absence and in combination with increasing concentrations of acetylsalicylic acid (ASA), was analyzed against the agonist arachidonic acid (AA), in platelet-rich plasma from healthy volunteers, using the Born spectrophotometric technique, which is based on the kinetics of platelet aggregation analyzed by turbidimetry (Born, 1962). The aggregometer allowed observing the changes in light transmission in the blood plasma after incubation with the test reagents and the platelet aggregation-inducing agent arachidonic acid (AA), so that the increase in the percentage of platelet aggregation was evident by the increase in light transmission through the cell, due to the platelets aggregating and settling at the bottom of the vessel. Considering that caffeic acid and chlorogenic acid are active metabolites with antiplatelet aggregation activity present in Solanum tuberosum, in this work we proposed to study the possible interactions that they exert when combined with the reference drug, acetylsalicylic acid, one of the most widely used agents in clinical practice. The objective was to determine whether they could exert coadjuvant effects as antiaggregants, which could eventually be useful in the therapy or prevention of atherothrombotic disorders. The results, under the experimental conditions set in this work, showed concentration- dependent effects of caffeic acid and chlorogenic acid, with effective concentrations 50 (IC50) of 1x10-3 and 3,4x10-4 M, respectively, while with ASA, in the range of concentrations tested, an antiaggregant effect was observed that decreases with increasing concentration (from 5,5x10-5 to 1,6x10-3M), which is consistent with its mechanism of action, antiaggregant at low concentrations and proaggregant at higher concentrations. When examining the interaction of caffeic acid (in the concentration range 1.5 - 3.0x10-4 M) with ASA (5.5x10-6M), an increase in the antiaggregation effect was observed that decreased with concentration, while the interaction of chlorogenic acid (in the range 2.26x10-4 - 5.6x10-3 M) with ASA (5.5x10-6M) did not show an increase in the antiaggregation effect, but rather a dose-dependent decrease. In conclusion, concentration-dependent antiaggregation effects are confirmed with the polyphenolic compounds caffeic acid and chlorogenic acid, a dose-dependent decreasing antiaggregation effect of ASA, and an interaction suggesting synergistic effect with caffeic acid; however, the sample size and concentration range need to be expanded to identify the appropriate range of concentrations of these compounds that exert possible synergistic effects when combined with ASA.