Oxidative Stress-Induced Platelet Apoptosis/Activation: Alleviation by Purified Curcumin via ASK1-JNK/p-38 Pathway

Biochemistry (Mosc). 2024 Mar;89(3):417-430. doi: 10.1134/S0006297924030039.

Abstract

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.

Keywords: activation and MAPKs protein; apoptosis; platelets; purified curcumin.

MeSH terms

  • Apoptosis* / drug effects
  • Blood Platelets* / drug effects
  • Blood Platelets* / metabolism
  • Curcumin* / analogs & derivatives
  • Curcumin* / chemistry
  • Curcumin* / pharmacology
  • Humans
  • MAP Kinase Kinase Kinase 5* / metabolism
  • MAP Kinase Signaling System / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Oxidative Stress* / drug effects
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects
  • Reactive Oxygen Species / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Curcumin
  • MAP Kinase Kinase Kinase 5
  • MAP3K5 protein, human
  • Reactive Oxygen Species
  • p38 Mitogen-Activated Protein Kinases