title: Plant food anthocyanins inhibit platelet granule secretion in hypercholesterolaemia: Involving the signalling pathway of PI3K-Akt.
abstract: 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.
authors: Fenglin
authors: F
authors: Song
authors: Yanna
authors: Y
authors: Zhu
authors: Zhenyin
authors: Z
authors: Shi
authors: Jinju
authors: J
authors: Tian
authors: Xiujuan
authors: X
authors: Deng
authors: Jing
authors: J
authors: Ren
authors: Marc C
authors: MC
authors: Andrews
authors: Heyu
authors: H
authors: Ni
authors: Wenhua
authors: W
authors: Ling
authors: Prof. Yan Yang, MD, PhD, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), No. 74, Zhongshan 2 Road, 510080 Guangzhou, PR China, Tel.: +86 20 87330687, E-mail: yangyan3@mail.sysu.edu.cn.
authors: Yan
authors: Y
authors: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000872:Anthocyanins / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000255:Adenosine Triphosphate; D000872:Anthocyanins; D001798:Blood Proteins; D002316:Cardiotonic Agents; D005960:Glucosides; D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C462279:cyanidin-3-O-beta-glucopyranoside; C494120:delphinidin 3-O-glucopyranoside; C494918:AKT1 protein, human
keywords: Hypercholesterolaemia; PI3K; anthocyanins; platelet granule