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Background: Platelet hyperactivity has a crucial role in initiating vascular thrombosis and subsequent cardiovascular disease (CVD)., Objective: This study aimed to assess the effect of anthocyanins (AC) on platelet aggregation and activation and lipid profile., Study Design: A total of 26 healthy participants consumed 320 mg of AC/day in the form of Medox® capsules for 28 days., Setting: This study was conducted in the laboratories of the School of Medical Sciences, Griffith University, Gold Coast, Australia., Participants: A total of 26 randomly recruited healthy 25- to 75-year-old participants completed this study., Primary Outcome Measures: Fasting blood samples were collected pre- and post-the intervention period to perform platelet activation studies by measuring platelet surface marker expression of CD41a and P-selectin, and platelet-monocyte aggregates in adenosine diphosphate (ADP) stimulated platelets. Platelet aggregation studies were performed by stimulating platelets with various agonists such as ADP, collagen and arachidonic acid. Full blood examination, coagulation and biochemistry profile analyses were also performed pre- and post-intervention. Flow cytometric analysis showed a significant effect of AC on the expression of P-selectin as measured by the platelet surface expression of CD62p., Results: There was a significant reduction of ADP-stimulated platelet aggregation. Hematologic analysis showed a significant reduction of mean platelet volume, mean cell hemoglobin, and mean cell hemoglobin concentration. Coagulation analysis demonstrated significant attenuation of fibrinogen level in the blood., Conclusion: This study showed inhibition of platelet activity, platelet aggregation and mean platelet volume (MPV). These results suggest that AC has a positive impact on attenuating platelet activity, which might minimize thrombotic risk.

Objective: The present research aimed to investigate the anti-inflammatory potential of dietary anthocyanin (ACN) in type 2 diabetic (T2D), T2D-at-risk and healthy individuals. Furthermore, dietary inflammatory index (DII) was used to study the association of diet with biomarkers of inflammation., Research Methods: An open-label clinical trial was conducted at Griffith University investigating the efficacy of 320 mg ACN supplementation per day over the course of 4 weeks. Diabetes-associated inflammatory biomarkers and relevant biochemical and physical parameters were tested pre-and post-intervention, and participants' dietary inflammatory potential was estimated., Results: A significant reduction in the pro-inflammatory biomarkers' interleukin-6, interleukin-18, and tumour necrosis factor-α was observed in the T2D group. In addition, some, but not all, biochemical parameters including fasting blood glucose, low-density lipoprotein cholesterol and uric acid were significantly improved in T2D-at-risk group. Moreover, a significant difference was detected between the DII scores of the healthy and T2D groups. DII score for the T2D group was consistent with an anti-inflammatory diet., Conclusion: Anti-inflammatory potential of dietary ACN in T2D participants was evidenced in the present study. Although, anti-inflammatory dietary patterns of T2D participants may have accelerated the anti-inflammatory effect of the ACN capsules supplemented in this trial.

Metabolic syndrome (MetS) is a global challenge for atherosclerosis. It was hypothesized that a four-week consumption of anthocyanin supplements by MetS patients who had three or more risk factors linked with metabolic syndrome would have a greater improvement in cardiometabolic biomarkers and would also reduce the risk of thrombosis. A total of 55 participants in two groups of Normal healthy and MetS (age 25-75y) were given 320 mg anthocyanin supplements twice daily for 4 weeks. Platelet coagulant activities, lipid profiles, fasting blood glucose, and inflammatory and oxidative stress biomarkers were measured before and after supplementation to evaluate the atheroprotective effects of anthocyanins in the study subjects. Four weeks of anthocyanin supplementation significantly decreased cardiometabolic risk factors including the average serum fasting blood glucose (FBG) (by 13.3%, P < .05) and lipid profiles by significant reduction in triglyceride (by 24.9%, P < .05) and LDL-C (by 33.1%, P < .05) in the MetS group. Anthocyanin supplementation also decreased high sensitivity C-reactive protein (hs-CRP) level (by 28%, P < .05) in females. However, no significant differences in serum UA (uric acid) and HDL-C were observed between anthocyanin pre- and post-treatment in both groups. Moreover, Anthocyanin supplements decreased ADP-induced platelet activation configuration expressed as P-selectin by 40% (P < .05). There was a positive correlation between decreased hs-CRP values and the levels of LDL-C and FBG in the MetS group (P < .05). These results support the hypothesis that anthocyanin supplementation exerts anti-atherogenicity effects by improving cardiometabolic risk factors and reducing thrombogenicity in the MetS population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Type 2 diabetes is associated with oxidative stress and low-grade inflammation resulting in endothelial dysfunction (ED). This study determined to explore the protective effects of berry-derived anthocyanins (AC) with potent antioxidant and anti-inflammatory activities in human diabetic endothelial cells upon oxidative and inflammatory stressors. Cultured healthy human aortic endothelial cells (HAEC) and diabetic human aortic endothelial cells (D-HAEC) exposed to oxidative stress by hydrogen peroxide (H 2 O 2 , 75 μM) and lipopolysaccharide (LPS, 1 μg/mL) as an inflammatory inducer before treatment with AC (50 μl/ml). The results from cytotoxicity assays showed that AC had no significant effects in cell viability (P-value < 0.0001), and exposure to H 2 O 2 75 μM had a less toxic effect (P-value < 0.05). Although, AC significantly decreased H 2 O 2 -induced cytotoxicity and oxidative stress in both HAEC and D-HAEC cell lines (P-value < 0.0001), no positive impact of AC was found on the GSSG/GSH ratios (P-value < 0.05). Exposure to the LPS increased the production of IL-6 in both HAEC and D-HAEC cell lines (P-value < 0.0001), whereas AC treatment reduced LPS-induced IL-6 production in both cell lines with a more robust impact on D-HAEC (P-value < 0.0001). While LPS increased inflammasome assembling and caspase-1 activation, AC treatment inhibited caspase-1 activation in D-HAEC (P ≤ 0.05). This study indicated that berry anthocyanins reduced oxidative stress and inflammation via the inhibition of the NF-ƙB signaling pathway, which contributes to mitigating the diabetes-induced up-regulation of NF-ƙB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Increased platelet activity plays a significant role in the development of arterial thrombosis and cardiovascular disease (CVD). Natural antioxidants including anthocyanin (AC) have gained considerable interest due to their hypothesized antithrombotic potential., Primary Study Objective: Our study aimed to examine the in vitro effect of AC compounds on platelet activation and aggregation., Methods: Fasting blood samples were collected from healthy volunteers (n = 13). A full blood examination was done to exclude any abnormal specimen. Flow cytometer assessed platelet activity by recording platelet surface markers expression of P-selectin (CD62P) and PAC-1. Platelet aggregation studies were performed by stimulating platelets using three different agonists adenosine diphosphate (ADP), collagen and arachidonic acid (AA)., Setting: The study was done in the school of Medical Sciences, Griffith University., Participants: Thirteen healthy adult participants were involved for blood collection., Intervention: AC was prepared using hemicellulose capsules sourced from Bilberries and Black Currants., Results: Anthocyanin (50 mg/L) significantly inhibited AA-induced platelet aggregation. Expression of P-selectin was significantly suppressed by 50 mg/L AC as measured by flow cytometer., Conclusions: AC attenuates platelet function by suppressing P-selectin expression and influencing Thromboxane A2 pathway (AA stimulation). These results provide further evidence for the effect of AC and the possible mechanism by which AC reduces platelet aggregation and activation. This study supports future human intervention trials to show that AC may act as a complement to other antiplatelet agents in reducing the risk of thrombosis.

Context • Type 2 diabetes mellitus is an independent precipitating factor for cardiovascular disease (CVD). Heart disease is one of the leading causes of mortality in patients with diabetes, mainly due to macrovascular complications, such as atherosclerosis. Although aspirin is a frequently used therapy for the inhibition of platelet hyperactivity, many studies suggest that aspirin resistance is rising. Objective • The study intended to investigate the benefits of anthocyanin (AC) as an antioxidant with inhibitory effects on platelets and, consequently, its potential usefulness as complementary antiplatelet therapy to attenuate the negative effects of atherosclerosis and CVD in patients with diabetes. Design • The research team performed a literature review. The team conducted a database search from 2007 to 2017 using Library of Congress, LISTA, PubMed, and Web of Science Core Collection databases, using the following keywords: anthocyanins, platelet, cardiovascular disease, and diabetes. Setting • The study took place at the School of Medical Sciences at Griffith University's Gold Coast campus (Southport, Australia). Results • Platelets have a major pathophysiological role of atherosclerosis and consequently CVD in diabetes. Antiplatelet drugs have a potent inhibitory effect of thrombotic and CVD risks in diabetes. Dietary antioxidants including ACs have a potential platelet inhibitory effect. Hence, ACs may act as complementary therapy to reduce CVD in diabetes. Conclusions • Although antiplatelet drugs such as aspirin provide significant action in the management of CVD, aspirin has limited benefits in diabetes. An AC antioxidant has a potential effect as an antiplatelet agent that subsequently can prevent atherosclerosis and CVD and, therefore, AC may be an alternative to other antiplatelet drugs such as aspirin. However, more interventional studies and large-scale clinical trials are necessary to prove the efficiency of AC as an alternative to other platelet-inhibitory drugs.

The anti-thrombotic properties of anthocyanin (ACN) supplementation was evaluated in this randomised, double-blind, placebo (PBO) controlled, cross-over design, dietary intervention trial in sedentary population. In all, sixteen participants (three males and thirteen females) consumed ACN (320 mg/d) or PBO capsules for 28 d followed by a 2-week wash-out period. Biomarkers of thrombogenesis and platelet activation induced by ADP; platelet aggregation induced by ADP, collagen and arachidonic acid; biochemical, lipid, inflammatory and coagulation profile were evaluated before and after supplementation. ACN supplementation reduced monocyte-platelet aggregate formation by 39 %; inhibited platelet endothelial cell adhesion molecule-1 expression by 14 %; reduced platelet activation-dependant conformational change and degranulation by reducing procaspase activating compound-1 (PAC-1) (↓10 %) and P-selectin expression (↓14 %), respectively; and reduced ADP-induced whole blood platelet aggregation by 29 %. Arachidonic acid and collagen-induced platelet aggregation; biochemical, lipid, inflammatory and coagulation parameters did not change post-ACN supplementation. PBO treatment did not have an effect on the parameters tested. The findings suggest that dietary ACN supplementation has the potential to alleviate biomarkers of thrombogenesis, platelet hyperactivation and hyper-aggregation in sedentary population.

Anthocyanins have been reported to induce the expression of enzymes involved in both cellular antioxidant defenses and attenuating inflammation-associated pathogenesis. Induction of such enzymes by edible anthocyanin largely accounts for their atherosclerosis chemo-protective activities. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an essential role in the coordinated induction of those genes encoding redox-responsive and cellular defense antioxidant enzyme termed antioxidant response element (ARE). Current studies have revealed that Nrf2-ARE signaling is involved in attenuating inflammation-associated pathogenesis such as atherosclerosis. Conversely, reduction in Nrf2 signaling leads to enhanced susceptibility to oxidative stress and inflammatory tissue injuries. The activation of Nrf2-ARE might inhibit the production of pro-inflammatory mediator including cyclooxygenase-2, chemokines, cytokines, cell adhesion molecules, and induction nitric oxide synthase. This review highlights the gene expression induced by dietary anthocyanin via Nrf2 signaling on redox-regulated transcription factor in atherosclerosis disorders., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The purpose of the study was to assess the effects of anthocyanin-rich Queen Garnet plum juice (QGPJ) on body weight and expression of leptin and adiponectin. Queen Garnet plum is a Japanese plum ( Prunus salicina ) cultivar developed through a Queensland Government breeding program with very high levels of anthocyanins (272 mg/100 g). Twenty healthy volunteers were supplemented with 200 ml/day of QGPJ and placebo drink for 4 weeks. Supplementation with QGPJ significantly reduces body weight and BMI ( p  < 0.05) with the average decrease of 0.6 kg in body weight and 0.2 units in BMI over the period of 4 weeks. Furthermore, consumption of QGPJ significantly increases adiponectin blood levels ( p  < 0.05) (average increase of 3.83 µg/mL) and decreases leptin blood levels (average decrease of 1.31 ng/mL). QGPJ may have potential to be used as a functional food for preventing obesity and obesity related disorders. [ABSTRACT FROM AUTHOR]

Increased oxidant production in humans induces a number of thrombotic consequences; including platelet hyperactivity/aggregability, which could be countered through specifically developed functional foods. We sought to determine the antithrombotic properties of anthocyanin-rich Queen Garnet plum juice (QGPJ) supplementation with and without exercise-induced oxidative stress. Thirteen healthy participants were investigated in a randomised, double-blind, placebo-controlled, cross-over trial. Participants consumed 200 mL/day of QGPJ and placebo juice for 28-days, with treatments separated by a two-week wash-out period. Blood samples were collected at baseline and after 1 h of exercise (70% peak-O 2 uptake) both before and after oral supplementation and evaluated for platelet function and haemostatic activity. QGPJ supplementation inhibited adenosine diphosphate-induced platelet aggregation both without and under exercise-induced oxidative stress by 10.7% (P < 0.01) and 12.7% (P < 0.001) respectively; arachidonic acid-induced aggregation under oxidative stress by 28.8% (P < 0.05); reduced platelet activation-dependant P-selectin expression by 32.9% (P < 0.01) and 38.7% (P < 0.001) both without and under oxidative stress respectively; and exhibited favourable effects on coagulation parameters both with and without oxidative stress. The anti-thrombotic activity exhibited by anthocyanin-rich QGPJ suggests a potential for cardiovascular disease risk reduction and may be considered as complementary anti-platelet nutritional therapy in pro-thrombotic population. [ABSTRACT FROM AUTHOR]

The anti-thrombotic properties of an anthocyanin-rich Queen Garnet plum juice (QGPJ) and anthocyanin-free prune juice (PJ) were studied in this randomised, double-blind, crossover trial. Twenty-one healthy subjects (M = 10, F = 11) consumed QGPJ, PJ or placebo, 200 mL/day for 28-days followed by a 2-week wash-out period. Only QGPJ supplementation inhibited platelet aggregation induced by ADP (<5%, P  = 0.02), collagen (<2.7%, P  < 0.001) and arachidonic acid (<4%, P  < 0.001); reduced platelet activation-dependent surface-marker P-selectin expression of activated de-granulated platelets (<17.2%, P  = 0.04); prolonged activated-partial thromboplastin clotting time (>2.1 s, P  = 0.03); reduced plasma-fibrinogen (<7.5%, P  = 0.02) and malondialdehyde levels, a plasma biomarker of oxidative stress ( P  = 0.016). PJ supplementation increased plasma hippuric acid content ( P  = 0.018). QGPJ or PJ supplementation did not affect blood cell counts, lipid profile, or inflammation markers. Our findings suggest that QGPJ but not PJ has the potential to significantly attenuate thrombosis by reducing platelet activation/hyper-coagulability and oxidative stress. [ABSTRACT FROM AUTHOR]

• Anthocyanin's anti-inflammatory properties were investigated. • ACN supplementation significantly decreases blood plasma levels of CCL2. • ACN supplementation significantly decreases blood plasma levels of IL-6. • ACN displays potential as a complementary anti-inflammatory therapeutic agent. Chronic low-grade inflammation in obese and overweight individuals is associated with an increased risk of type II diabetes and cardiovascular disease. The current trial investigated the anti-inflammatory properties of anthocyanin (ACN) supplementation in lean, overweight and obese individuals. Fifteen lean, ten overweight and ten obese participants consumed ACN (320 mg/day) for 28 days along with their usual diet. ACN supplementation significantly decreased blood plasma levels of CCL2 in the lean, overweight and obese groups (p < 0.0001, p < 0.0001 and p < 0.01 respectively). Additionally, significantly decreased levels of IL-6 in the obese group (p < 0.05) were also observed post-ACN supplementation. In conclusion, these results demonstrate the anti-inflammatory potential of ACN and suggest the supplementation of ACN as a complementary therapeutic agent for reducing chronic inflammation in obese and overweight individuals. [ABSTRACT FROM AUTHOR]