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

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Kurnegala Manikanta^1#, Manoj Paul^1#, Vaddaragudisalu D. Sandesha¹, Shanmuga S. Mahalingam², Thimmasandra Narayan Ramesh³, Krishnegowda Harishkumar⁴, Shashank S Koundinya⁵, Shivanna Naveen⁶, Kempaiah Kemparaju^1,a*, and Kesturu S. Girish^7,b*

¹Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru-570 006, India

²Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH 44106, USA

³Department of Studies and Research in Chemistry, University College of Science, Tumkur University, Tumakuru 572 103, India

⁴Department of Biotechnology, Yuvaraja’s College, University of Mysore, Mysore-570 005, India

⁵All India Institute of Medical Science, Sri Aurobindo Marg, Ansari Nagar, East, New Delhi-110029, India

⁶Applied Nutrition Discipline, Defense Food Research Laboratory, Mysuru, 570 011, India

⁷Department of Studies and Research in Biochemistry, Tumkur University, Tumakuru-572 103, India

Received September 26, 2023; Revised November 26, 2023; Accepted January 29, 2024

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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.

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KEY WORDS: platelets, purified curcumin, apoptosis, activation and MAPKs protein

DOI: 10.1134/S0006297924030039

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