Açaí juice attenuates atherosclerosis in ApoE deficient mice through antioxidant and anti-inflammatory activities

doi:10.1016/j.atherosclerosis.2011.02.035

Atherosclerosis

Volume 216, Issue 2, June 2011, Pages 327-333

https://doi.org/10.1016/j.atherosclerosis.2011.02.035 Get rights and content

Abstract

Objective

Açaí fruit pulp has received much attention because of its high antioxidant capacity and potential anti-inflammatory effects. In this study, athero-protective effects of açaí juice were investigated in apolipoprotein E deficient (apoE^−/−) mice.

Methods and results

ApoE^−/− mice were fed AIN-93G diet (CD) or CD formulated to contain 5% freeze-dried açaí juice powder (AJ) for 20 weeks. The mean lesion areas in the aorta for apoE^−/− mice fed AJ were 58% less (P < 0.001) compared to that for CD fed mice. HDL-cholesterol was higher in AJ fed mice. Biomarkers of lipid peroxidation, including F₂-isoprostanes and isomers of hydroxyoctadecadienoic acids and hydroxyeicosatetraenoic acids were significantly lower in serum and in liver of AJ fed mice. Expression of the two antioxidant enzyme genes, Gpx3 and Gsr, were significantly up-regulated in the aorta from AJ fed mice. The activity of GPX, GSR and PON1 increased in serum and/or liver of mice fed AJ. In the second experiment, ApoE^−/− mice were fed CD or AJ for 5 weeks. Serum levels, gene expression and protein levels of the two proinflammatory cytokines TNF-α and IL-6 in the resident macrophages with or without LPS stimulation were lower in mice fed AJ. SEAP reporter assay determined that AJ reduced NF-κB activation.

Conclusion

Reducing lipid peroxidation through boosting antioxidant enzymes and inhibiting pro-inflammatory cytokine production are proposed as major underlying mechanisms for the athero-protective effects of the açaí juice tested in these experimental in vivo models.

Introduction

Cardiovascular diseases remain the leading cause of death not only in the United States but also in most of the industrialized world [1], [2]. It has long been recognized that a diet rich in fruits and vegetables may have beneficial effects on cardiovascular diseases, largely attributed to their antioxidant and anti-inflammatory properties [3], [4], [5]. However, in vivo experimental evidence that consumption of specific fruits and vegetables reduces the risk of cardiovascular disease based on plausible underlying mechanisms remain scarce.

Açaí (Euterpe oleracea Mart.) belongs to the family Arecaceae (palm tree). It is indigenous to South America especially in the Amazon flood plains. Açaí pulp has received much attention in recent years as one of the new “superfruits”. It exhibits high antioxidant capacity and has been used as a food ingredient with functional contributions to the diet beyond its basic nutritional composition [6], [7], [8]. In a recent paper, diet supplementation with açaí pulp was found to improve biomarkers of oxidative stress resulting in a hypocholesterolemic effect in rats [9]. This suggested that consumption of açaí could improve antioxidant status and provide athero-protective effects in an animal model of hypercholesterolemia. Açaí pulp or açaí juice has also been shown to possess anti-inflammatory activity [10]. Freeze-dried açaí pulp inhibited the activity of cyclooxygenase (COX)-1 and -2 in vitro, with greater efficacy against COX-1 [8]. Açaí extracts inhibited lipopolysaccharide- and interferon-g-induced nitric oxide production by reducing the expression of inducible nitric oxide synthase (iNOS) expression [11]. Consumption of a juice blend containing açai as the main component has demonstrated in vivo anti-inflammatory properties in human subjects based on a randomized, double-blind, placebo controlled cross-over study [7]. These findings suggest possible cardio-protective properties of açaí.

In this study, the athero-protective effects of a freeze-dried and frozen açaí pulp juice mixture were studied in the apolipoprotein deficient (apoE^−/−) mouse model. The apoE^−/− mouse model has been a useful model to study the mechanisms of action related to atherosclerosis in cardiovascular research [12]. The underlying mechanisms were also explored with primary emphases on the fruit's antioxidant and anti-inflammatory activities.

Section snippets

Experimental materials and animal

The açaí juice blend was provided by MonaVie, LLC (South Jordan, UT). This blend contains açaí (Euterpe oleracea Mart.) freeze-dried and frozen pulp (Earthfruits, South Jordan, UT) as the predominant ingredient. This juice blend has been characterized as containing polyphenols as major phytochemicals previously [7]. The chromatograms of polyphenol profiles of this açaí juice and freeze-dried açaí pulp were presented as supplemental data (Fig. S1). To precisely control the intake, the juice

Growth and body composition

Mean body weight of AJ fed mice was higher (P < 0.001) than that of CD fed mice (Table 1). NMR analysis showed that body fat content and lean body mass did not differ significantly between CD and AJ fed mice (Table 1).

Plasma lipid profile

Plasma levels of total, LDL- and HDL-cholesterol, and triglyceride were analyzed (Table 1). HDL cholesterol levels were significantly greater (P < 0.01) in AJ fed group. Total cholesterol, LDL cholesterol and triglyceride did not differ between the groups.

Atherosclerotic lesion measurement

Enface analysis of the

Discussion

In this study, we provide direct experimental evidence showing that a diet containing an açaí juice at the dose of 5% developed significantly less atherosclerotic lesions in the apoE^−/− mice model (Fig. 1). Descending aorta was used for measuring lesion areas because the lesions developed throughout the aorta and its principal branches in this model [18]. AJ diet did not change body composition despite a significant gain in body weight, nor did it alter total cholesterol, LDL-cholesterol or

Acknowledgement

The authors express our appreciation for financial support by MonaVie LLC (South Jordan, UT, USA).

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As the cardiovascular system ages, it becomes more vulnerable to the effects of oxidative stress and inflammation. The aging process, along with external factors such as radiation exposure and lifestyle, induces vascular senescence and accelerates atherosclerotic plaque accumulation. Expression of nicotinamide adenine dinucleotide phosphate oxidase 1 (Nox1), which produces superoxide, is associated with senescence in vascular smooth muscle cells in vitro and atherosclerosis in ApoE^−/− mice in vivo. However, it is unknown whether Nox1 could be down-regulated by nutritional interventions aimed to reduce atherosclerosis. Here we study the effect of blackberry supplementation in Nox1 expression and atherosclerosis. Four-month-old ApoE^−/− male and female mice were fed low-fat, high-fat or high-fat supplemented with 2% freeze-dried blackberry powder diets for 5 weeks. Analysis of the aorta showed that diet supplemented with blackberry significantly decreased plaque accumulation, senescence associated-β-galactosidase and Nox1 expression in the aorta of male but not female mice. The lipid profile was unchanged by blackberry in both female and male animals. Thus, the known role of Nox1 in atherosclerosis suggests that the atheroprotective effect of blackberry is mediated by Nox1 down-regulation in male mice and that Nox1 is regulated in a gender-dependent manner in females.
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There are several diseases, such as bipolar disorder, for example, where a chronic inflammation related to NLRP3 inflammasome is present. So, it is important to search for new anti-inflammatory agents. Açaí (Euterpe oleracea Mart.) is a Brazilian fruit with antioxidant and anti-inflammatory activities. However, the mechanism of açaí anti-inflammatory potential is still unclear. The objective of this study was to evaluate the anti-inflammatory effect of açaí extract and its mechanism. Macrophages were exposed to phytohemagglutinin to induce inflammation and treated with different concentrations of açaí extract. Cellular proliferation, cell cycle, oxidative metabolism parameters, inflammatory cytokines and NLRP3 have been assessed. 1 μg/mL of açaí extract was able to act as an antioxidant agent. Açaí extract decreased NLRP3 inflammasome levels and reduced pro-inflammatory cytokines. The extract caused cell cycle arresting and decreased proliferation. Obtained results suggest that açaí extract has anti-inflammatory effect and its mechanism of action involve NLRP3 inflammasome modulation.
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The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food.
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Citation Excerpt :
Consequently these results revealed that β-elemene attenuated endothelial dysfunction in HUVECs by activating the Akt/eNOS pathway and then leading to NO production in vitro. Various studies demonstrated that atherosclerotic lesion development in ApoE−/− mice is inhibited by antioxidant and anti-inflammatory properties [27]. Our previous reports presented that β-elemene inhibited atherosclerosis in experimental atherosclerotic rabbits and protected against oxidative stress induced endothelial injury in HUVECs [16,17].
β-Elemene is a major bioactive sesquiterpenoids compound isolated from the essential oils of Curcuma Wenyujin, a Chinese medicinal herb that treats tumor in clinics. However anti-atherosclerotic effects of β-elemene have not been fully investigated in vivo. The objective of this study is to further elucidate the anti-atherosclerotic activities of β-elemene in ApoE^−/− mice. Staining techniques and immunohistochemistry were used to validate atherosclerosis. Serum lipids, plasma nitrite and nitrate were analyzed by colorometric methods. ROS and antioxidative enzymes were measured through kits. Proteome profiler array was performed to analyze atherosclerosis-related inflammatory Cytokine. Western blot was used for measuring various proteins expressions. These results revealed that β-elemene inhibited atherosclerotic lesion size and increased stability of plaques in ApoE^−/− mice by alleviating levels of vascular oxidative stress and preventing pro-inflammatory cytokine production. In addition β-elemene maintained endothelial function by significantly improving plasma nitrite and nitrate levels and expression of phosphorylation-eNOS in vivo. β-elemene also increased the production of the nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs) and promoted phosphorylation of eNOS^ser1177 and Akt in vitro. In Conclusive, data revealed that β-elemene attenuated atherosclerosis and enhanced stability of plaques at least partially through its antioxidative and anti-inflammatory features and protected against endothelial dysfunction in ApoE^−/− mice.

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^☆: Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture.

¹: These two authors contributed equally to this work.

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Açaí juice attenuates atherosclerosis in ApoE deficient mice through antioxidant and anti-inflammatory activities☆

Abstract

Objective

Methods and results

Conclusion

Introduction

Section snippets

Experimental materials and animal

Growth and body composition

Plasma lipid profile

Atherosclerotic lesion measurement

Discussion

Acknowledgement

Lancet

Am J Clin Nutr

J Ethnopharmacol

J Nutr

Free Radic Biol Med

J Nutr

Atherosclerosis

J Biol Chem

Biochem Biophys Res Commun

Free Radic Biol Med

Shattuck lecture—cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities

N Engl J Med

Fruits, vegetables and coronary heart disease

Nat Rev Cardiol

Dietary effects on oxidation of low-density lipoprotein and atherogenesis

Curr Atheroscl Rep

Increased antioxidant capacity and inhibition of lipid peroxidation in healthy adults consuming an acai (Euterpe oleracea) fruit-based juice

Acta Hortic

In vitro and in vivo antioxidant and anti-inflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study

J Agric Food Chem

Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleracea Mart. (acai)

J Agric Food Chem

Bioactive compounds and antioxidant activity on fruits from different acai (Euterpe oleracea Mart) progenies

Acta Hortic

Açai (Euterpe oleracea): an Amazonian palm fruit with broad antioxidant and anti-inflammatory activities

Flavor and Health Benefits of Small Fruits, Washington