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Biochemistry (Mosc) ; 89(3): 417-430, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38648762

RESUMEN

Platelets are known for their indispensable role in hemostasis and thrombosis. However, alteration in platelet function due to oxidative stress is known to mediate various health complications, including cardiovascular diseases and other health complications. To date, several synthetic molecules have displayed antiplatelet activity; however, their uses are associated with bleeding and other adverse effects. The commercially available curcumin is generally a mixture of three curcuminoids: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Although crude curcumin is known to inhibit platelet aggregation, the effect of purified curcumin on platelet apoptosis, activation, and aggregation remains unclear. Therefore, in this study, curcumin was purified from a crude curcumin mixture and the effects of this preparation on the oxidative stress-induced platelet apoptosis and activation was evaluated. 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH) compound was used as an inducer of oxidative stress. Purified curcumin restored AAPH-induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release from mitochondria to the cytosol, and phosphatidyl serine externalization. Further, it inhibited the agonist-induced platelet activation and aggregation, demonstrating its antiplatelet activity. Western blot analysis confirms protective effect of the purified curcumin against oxidative stress-induced platelet apoptosis and activation via downregulation of MAPKs protein activation, including ASK1, JNK, and p-38. Together, these results suggest that the purified curcumin could be a potential therapeutic bioactive molecule to treat the oxidative stress-induced platelet activation, apoptosis, and associated complications.


Asunto(s)
Apoptosis , Plaquetas , Curcumina , MAP Quinasa Quinasa Quinasa 5 , Estrés Oxidativo , Curcumina/farmacología , Curcumina/análogos & derivados , Curcumina/química , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , MAP Quinasa Quinasa Quinasa 5/metabolismo , Humanos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Activación Plaquetaria/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos
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