Plant food anthocyanins inhibit platelet granule secretion in hypercholesterolaemia: Involving the signalling pathway of PI3K-Akt

Thromb Haemost. 2014 Nov;112(5):981-91. doi: 10.1160/TH13-12-1002. Epub 2014 Jul 31.


Controlling platelet granule secretion has been considered an effective strategy to dampen thrombosis and prevent atherosclerosis. Anthocyanins are natural plant pigments and possess a wide range of biological activities, including cardiovascular protective activity. In the present study we explored the effects and the potential mechanisms of anthocyanins on platelet granule secretion in hypercholesterolemia. In a randomised, double-blind clinical trial, 150 hypercholesterolaemic individuals were treated with purified anthocyanins (320 mg/day) or placebo for 24 weeks. Anthocyanins consumption significantly reduced plasma levels of β-thromboglobulin (β-TG), soluble P-selectin, and of Regulated on Activation Normal T cell Expressed and Secreted (RANTES) as compared with the placebo. A minor reduction in platelet factor 4 (PF4) and transforming growth factor β1 (TGF-β1) levels were also observed. In in vitro experiments, we observed that puriӿed anthocyanin mixture, as well as its two main anthocyanin components, delphinidin-3-glucoside (Dp-3-g) and cyanidin-3-glucoside (Cy-3g) directly inhibited platelet á-granule, dense granule, and lysosome secretion evaluated by P-selectin, RANTES, β-TG, PF4, TGF-β1, serotonin, ATP, and CD63 release. Further, anthocyanins inhibited platelet PI3K/Akt activation and consequently attenuated eNOS phosphorylation and cGMP production, thus interrupting MAPK activation. LY294002, a PI3K inhibitor, did not cause additional inhibitory efficacy, indicating that anthocyanin-induced effects may be involved in inhibition of the PI3K/Akt signalling pathway. These results provide evidence that by inhibiting platelet granule secretion, anthocyanins may be a potent cardioprotective agent.

Keywords: Hypercholesterolaemia; PI3K; anthocyanins; platelet granule.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Anthocyanins / pharmacology
  • Anthocyanins / therapeutic use*
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blood Proteins / metabolism
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cytoplasmic Granules / metabolism
  • Double-Blind Method
  • Female
  • Glucosides / pharmacology
  • Glucosides / therapeutic use
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lysosomes / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphorylation / drug effects
  • Phytotherapy*
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-akt / physiology*
  • Signal Transduction / drug effects*


  • Anthocyanins
  • Blood Proteins
  • Cardiotonic Agents
  • Glucosides
  • Intercellular Signaling Peptides and Proteins
  • cyanidin-3-O-beta-glucopyranoside
  • delphinidin 3-O-glucopyranoside
  • Adenosine Triphosphate
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt