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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.

BackgroundIt is becoming increasingly evident that platelet chemokines are involved in distinct aspects of atherosclerosis. The aim of this study was to examine the effects of long-term supplementation with purified anthocyanins on platelet chemokines in hypercholesterolemic individuals and to identify correlations of decreased platelet chemokine levels with serum lipid and inflammatory marker levels.MethodsA total of 146 hypercholesterolemic individuals were recruited and treated with 320 mg of purified anthocyanins (n = 73) or a placebo (n = 73) daily for 24 weeks in this randomized, double-blind, placebo-controlled trial.ResultsAnthocyanin supplementation for 24 weeks significantly decreased the plasma CXCL7 (–12.32% vs. 4.22%, P = 0.001), CXCL5 (–9.95% vs. 1.93%, P = 0.011), CXCL8 (–6.07% vs. 0.66%, P = 0.004), CXCL12 (–8.11% vs. 5.43%, P = 0.023) and CCL2 levels (–11.63% vs. 12.84%, P = 0.001) compared with the placebo. Interestingly, the decreases in the CXCL7 and CCL2 levels were both positively correlated with the decreases in the serum low-density lipoprotein-cholesterol (LDL-C), high-sensitivity C-reactive protein (hsCRP) and interleukin-1β (IL-1β) levels after anthocyanin supplementation for 24 weeks. The decrease in the CXCL8 level was negatively correlated with the increase in the how-density lipoprotein-cholesterol (HDL-C) level and was positively correlated with the decrease in the soluble P-selectin (sP-selectin) level in the anthocyanin group. In addition, a positive correlation was observed between the decreases in the CXCL12 and tumornecrosis factor-α (TNF-α) levels after anthocyanin supplementation. However, the plasma CXCL4L1, CXCL1, macrophage migration inhibitory factor (MIF) and human plasminogen activator inhibitor 1 (PAI-1) levels did not significantly change following anthocyanin supplementation.ConclusionsThe present study supports the notion that platelet chemokines are promising targets of anthocyanins in the prevention of atherosclerosis.Trial registration ChiCTR-TRC-08000240. Registered: 10 December 2008.

In order to find new sources of natural antioxidants, the antioxidant capacities of 50 medicinal plants associated with treatment of rheumatic diseases were systemically evaluated using the ferric-reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays, and their total phenolic contents were measured by the Folin–Ciocalteu method. Their antioxidant activities of some of these plants were analyzed for the first time. The FRAP and TEAC assay results suggested that the antioxidant compounds in these plants possessed free radicals scavenging activity and oxidant reducing power. A positive linear correlation between antioxidant capacities and total phenolic contents implied that phenolic compounds in these plants could be the main components contributing to the observed activities. The results showed that Geranium wilfordii, Loranthus parasiticus, Polygonum aviculare, Pyrrosia sheaeri, Sinomenium acutum and Tripterygium wilfordii possessed the highest antioxidant capacities and total phenolic content among 50 plants tested, and could be rich potential sources of natural antioxidants.