Antiplatelet activity of astaxanthin in control- and high cholesterol-fed rats mediated by down-regulation of P2Y₁₂, inhibition of NF-κB, and increasing intracellular levels of cAMP

Abstract

This study evaluated the antiplatelet effect of the plant carotenoid, astaxanthin (ASTX) in rats fed either control or high cholesterol plus cholic acid diet (HCCD) and possible underlying mechanisms. Adult male Wistar rats were divided into four groups (n = 8/each), namely, control (fed normal diet), control + ASTX (10 mg/kg/day), HCCD-fed rats, and HCCD + ASTX-treated rats. Diets and treatments were orally administered daily for 30 days. In both control and HCCD-fed rats, ASTX significantly increased fecal levels of triglycerides and cholesterol, reduced platelet count, prolonged bleeding time, and inhibited platelet aggregation. It also reduced platelet levels of reactive oxygen species (ROS) and Bcl-2; thromboxane B2 (TXB2) release; and the expression of P2Y₁₂, P-selectin, and CD36 receptors. Moreover, the activity NF-κB p65 and Akt was inhibited. Concomitantly, it increased the protein levels of cleaved caspase-3 and vasodilator-stimulated phosphoprotein (p-VASP) as well as intracellular levels of cAMP. However, in HCCD-fed rats, the effects of ASTX were associated with reduced serum levels of ox-LDL-c and fasting plasma glucose levels. In conclusion, antiplatelet effects of ASTX involve ROS scavenging, inhibiting NF-κB activity, down-regulating P2Y₁₂ expression, and increasing intracellular levels of cAMP that are attributed to its antioxidant, hypolipidemic, and anti-inflammatory effects.

Keywords:

• Astaxanthin
• NF-κB inhibition
• P2Y12 down-regulation
• platelet aggregation

Acknowledgements

The authors wish to thank the technical staff of the animal house at the College of Medicine at KKU for their help in the management, care, and feeding of the animals used in this study. In addition, the authors wish to thank the technical staff at the Department of Biochemistry and the Department of Physiology, College of Medicine at KKU, for their assistance with biochemical measurements.

Disclosure statement

The authors declare that there is no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Funding

This study is funded by King Khalid University (KKU) through general research project. grant number [188/1440].