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      Dose-dependent effects of anthocyanin supplementation on platelet function in subjects with dyslipidemia: A randomized clinical trial

      research-article
      a , b , c , a , b , c , e , a , b , c , f , a , b , c , a , b , c , b , c , d , g , a , b , c , a , b , c , a , b , c , b , c , d , a , b , c , *
      EBioMedicine
      Elsevier
      Anthocyanins, Platelet function, Oxidative stress, Dose-dependent effects, Randomized controlled trial, ROS, reactive oxygen species, ASCVD, atherosclerotic cardiovascular disease, IPAQ, International Physical Activity Questionnaire, BW, body weight, BH, body height, NC, neck circumference, WC, waist circumference, WHR, waist-hip ratio, HC, hip circumference, HR, heart rate, BP, blood pressure, EDTA, ethylene diamine tetraacetic acid, PRP, platelet-rich plasma, LDL-C, low-density lipoprotein cholesterol, HDL-C, high-density lipoprotein cholesterol, TG, triglyceride, TC, total cholesterol, ApoA-1, apolipoprotein A-1, ApoB, apolipoprotein B, FBG, fasting blood glucose, FINS, fasting insulin, UA, uric acid, HOMA-IR, insulin resistance, PT, prothrombin time, APTT, activated partial thromboplastin time, TT, thrombin clotting time, Fib, fibrinogen, MDA, malondialdehyde, TSOD, total superoxide dismutase, 8-iso-PGF2α, 8-iso-prostaglandin F2α, ANOVA, analysis of variance, SEM, standard error of the mean, ACN, anthocyanin

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          Abstract

          Background

          Dyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia.

          Methods

          A double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks.

          Findings

          Compared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) ( P < 0.05). Moreover, compared to placebo group, anthocyanins at 320 mg/day inhibited collagen-induced platelet aggregation (-7.05±2.38%), ADP-induced platelet aggregation (-7.14±2.00%), platelet ROS levels (-14.55±1.86%), and mitochondrial membrane potential (7.40±1.56%) ( P < 0.05). There were dose-response relationships between anthocyanins and the attenuation of platelet aggregation, mitochondrial membrane potential and ROS levels ( P for trend <0.05). Furthermore, significantly positive correlations were observed between changes in collagen-induced (r = 0.473) or ADP-induced (r = 0.551) platelet aggregation and ROS levels in subjects with dyslipidemia after the 12-week intervention ( P < 0.05).

          Interpretation

          Anthocyanin supplementation dose-dependently attenuates platelet function, and 12-week supplementation with 80 mg/day or more of anthocyanins can reduce platelet function in individuals with dyslipidemia.

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          Most cited references54

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          Dyslipidemia in Obesity: Mechanisms and Potential Targets

          Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia.
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            A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice.

            The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of diet-induced T2D. Importantly, cranberry (Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota.
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              Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries.

              The antioxidant activity of phenolics in fruits of blueberry (Vaccinium corymbosum cv. Sierra), cranberry (Vaccinium macrocarpon cv. Ben Lear), wild chokeberry (Aronia melanocarpa), and lingonberry (Vaccinium vitis-idaea cv. Amberland) was determined in this study. The phenolic constituents and contents among the different berries varied considerably. Anthocyanins were found to be the main components in all these berries. Chlorogenic acid in blueberry, quercetin glycosides in cranberry and lingonberry, and caffeic acid and its derivative in chokeberry were also present in relatively high concentrations. Chlorogenic acid, peonidin 3-galactoside, cyanidin 3-galactoside, and cyanidin 3-galactoside were the most important antioxidants in blueberry, cranberry, wild chokeberry, and lingonberry, respectively. The contribution of individual phenolics to the total antioxidant capacity was generally dependent on their structure and content in the berries. Phenolics such as quercetin and cyanidin, with 3',4'-dihydroxy substituents in the B ring and conjugation between the A and B rings, had highly effective radical scavenging structures in blueberries, cranberries, chokeberries, and lingonberries. Phenolic acids such as caffeic acid also showed high antioxidant activity, probably due to its dihydroxylation in the 3,4 positions as hydrogen donors.
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                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                12 August 2021
                August 2021
                12 August 2021
                : 70
                : 103533
                Affiliations
                [a ]School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province 518106, PR China
                [b ]Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, Guangdong Province 510080, PR China
                [c ]Guangdong Engineering Technology Center of Nutrition Transformation, Guangzhou, Guangdong Province 510080, PR China
                [d ]Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province 510080, PR China
                [e ]Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province 518107, PR China
                [f ]The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province 518033, PR China
                [g ]Institute of Preventive Medicine, School of Public Health, Dali University, Dali, Yunnan 671000, PR China
                Author notes
                [* ]Corresponding author at: School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province 518106, PR China. yangyan3@ 123456mail.sysu.edu.cn
                Article
                S2352-3964(21)00326-1 103533
                10.1016/j.ebiom.2021.103533
                8374375
                34392146
                4fb93c2a-2b89-40b9-8050-2fc20b774873
                © 2021 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 25 April 2021
                : 26 July 2021
                : 26 July 2021
                Categories
                Research Paper

                anthocyanins,platelet function,oxidative stress,dose-dependent effects,randomized controlled trial,ros, reactive oxygen species,ascvd, atherosclerotic cardiovascular disease,ipaq, international physical activity questionnaire,bw, body weight,bh, body height,nc, neck circumference,wc, waist circumference,whr, waist-hip ratio,hc, hip circumference,hr, heart rate,bp, blood pressure,edta, ethylene diamine tetraacetic acid,prp, platelet-rich plasma,ldl-c, low-density lipoprotein cholesterol,hdl-c, high-density lipoprotein cholesterol,tg, triglyceride,tc, total cholesterol,apoa-1, apolipoprotein a-1,apob, apolipoprotein b,fbg, fasting blood glucose,fins, fasting insulin,ua, uric acid,homa-ir, insulin resistance,pt, prothrombin time,aptt, activated partial thromboplastin time,tt, thrombin clotting time,fib, fibrinogen,mda, malondialdehyde,tsod, total superoxide dismutase,8-iso-pgf2α, 8-iso-prostaglandin f2α,anova, analysis of variance,sem, standard error of the mean,acn, anthocyanin

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