Anthocyanins and anti-inflammatory effects -
This review included CTs that evaluated inflammation markers altered by obesity conditions in volunteers receiving fruits, extracts, juices, or tablets rich in ACNs. The CTs were conducted for up to 24 weeks with a maximum daily ACN dose of 1, mg.
The main objective of these interventions focused on evaluating the beneficial effects of ACNs on anthropometric parameters e. However, the specific anthocyanin effect remains unclear.
To graphically depict the most represented and modified markers studied in the reviewed literature, data from CTs can be observed in Figure 2. This heatmap shows how the distinct ACN sources changed the measured markers in the selected studies.
Among them, five reported the quantity of the ACN source fruit or extract without specifying ACN determination 56 — 60 , 19 reported the total ACN content of applied doses 61 — 79 , eight reported total and individual ACN concentrations 40 , 41 , 44 — 46 , 52 , 53 , 55 , and 17 used the Medox ® dietary supplement 51 , 80 — Measurements of markers directly related to lipid metabolism are the most represented data, followed by inflammation markers such as interleukins 6 and 10 IL-6 and IL and tumor necrosis factor α TNFα.
Regarding administered ACNs, it can be observed that there is a great variation in part due to acylated ACN and proanthocyanidin content being heterogeneous. As the color code indicates, determinations for C-reactive protein CRP 67 , high-density lipoprotein HDL 79 , and insulin 59 showed the most significant changes.
As basal concentrations of analyzed markers varied among cohorts, data from healthy subject cohorts were not included in Figure 2 but were analyzed separately. Kaspar et al. As this trial was the only one that reported an increase in IL-6 levels, it is possible that the high petunidin content 42 in purple potatoes may be connected to that change.
Guo et al. Ivanova et al. infusion 4 mg cyanidin daily for 4 weeks produced a decrease in LDL and TG levels The reported ACN dose by Ivanova et al.
Principal components analysis PCA is a technique that allows the reduction of dimensions of datasets containing multiple features per observation. Thus, the PCA technique was used because the obtained dataset contained many variables related to each study. Figure 3A shows a PCA from 39 of the 49 included studies in Figure 2 , where data from calculated ACN doses and shifts produced in measured markers were studied.
Two principal components explained From the PCA, it was observed that most of the studies with high variances blue group in Figure 3A were those in which the highest ACN doses among included studies were used 46 , 56 , 64 , 69 , 84 , 91 , 93 , To avoid the doses being the main variable describing variance, PCA was performed excluding ACN doses.
Figure 3B , describing Hypothesizing that high variance in both PCAs should reflect the accurate determination of concentrations and their effects, details of CTs in such cases are mentioned. Trials by Zunino et al. On the other hand, Li et al.
Figure 3. Principal component analysis PCA of data from Figure 2 studying cohorts with pathologies including A or not B single anthocyanin doses as factors. C Correlation of HDL with delphinidin doses in trials included in A, B. A The Red group represents trials with low variance and the blue group represents trials with high variance.
B The red group represents trials with low variance, the blue group represents trials with high variance in A, B , the green group represents trials with high variance that used Medox ® , and the purple group represents trials with high variance that used uncharacterized or partially characterized anthocyanin sources.
Besides the studies with high variances in Figures 3A , B , the highest variances in Figure 3B were found in trials using Medox ® green group 80 , 82 , 87 , 88 and interventions with cyanidin, malvidin, and petunidin, as main components purple group 45 , 63 , 73 , Trials by Hassellund et al.
Although Chan et al. Interestingly, the four studies 63 , 82 , 87 , 88 shared interventions using predominantly delphinidin but only the trial using the cohort with diabetes found a significant CRP drop.
This fact may point toward an important function for CRP as a sensitive marker for future research addressing the ACN effect in cohorts with diabetes. Intervention times among the trials using uncharacterized ACN sources with positive values for PC1 ranged from 4 to 8.
Doses did not correlate with the found variance since the study by Kianbakht et al. While Soltani et al. The most crucial difference between the trials may be the cohorts since subjects in Kianbakht et al.
This difference may explain why Kianbakht et al. using a low dose of ACN tablets 2. The results among the studies with higher variances in PCAs reflected that concentrations of single ACNs in the database could not be completely correlated with observed effects.
Moreover, certain differences suggested that greater changes in markers were associated with their higher initial baseline and severity of the diseases in the studied cohorts.
To evaluate the effect of increased baseline levels, the correlation of the most common obesity-related inflammation markers with single ACN supplementation doses was assessed Supplementary Figure S1. Although the performed analysis showed that HDL, LDL, and TG levels were the most modified values by all ACNs, HDL level was the only parameter significantly correlated with delphinidin doses Figure 3C.
Specifically, observations made from trials with diabetic subjects encourage future research to dissect the effects of delphinidin and the mechanisms of action in these cohorts. The poor correlation found for most ACNs may be due to several factors, namely, the influence of the ACN-free fraction, synergic or additive effects from other ACNs, and modified bioavailability among different matrices.
As comparisons made among the complete dataset did not produce conclusive data and doses of single ACNs should be homogenous in CTs in which only Medox ® was used, a PCA was performed on a subset of these CTs. Figures 4A , B shows PCAs for complete including dosing, Figure 4A and only markers ACN doses not included, Figure 4B data.
When dosing was incorporated into the analysis Figure 4A , PC1 comprised predominantly ACN doses and described As observed in the global analysis of CT, including dosing, studies from the research group of Li, Zhang, Zhu, and co-workers 91 , 93 , 95 showed high variance Figure 4A , green group in the opposite way to the trial in which the lowest ACN quantity was tested purple dot CT with moderate variance 82 , 87 , 88 also appeared separated from the central cluster in both PCAs blue group in Figures 4A , B.
When ACN dosing data were excluded from this analysis Figure 4B , only five trials conserved high variance blue and green groups 80 , 82 , 84 , 87 , When dosing was not included in PCA, two main factors explained A CT conducted by Hassellund et al.
As other markers were unaffected in the Hasselllund study, increased glucose level determined its main variance. On the other hand, Yang et al. Similarly, Yang et al. Li et al.
Differences between the results of the mentioned trials may be attributed to the status of diabetes progression or the treatment duration. Future CTs including stratification of the diabetes stages and Medox ® supplementation for 12, 18, and 24 weeks would clarify the impact of each factor.
Figure 4. Principal component analysis of clinical trials addressing obesity-related inflammation in Medox ® A, B or uncharacterized C, D subsets. Analyses A, C included single anthocyanin doses as factors while B, D analyses did not.
Colors are used to separate groups of trials discussed in the text. A The red group represents trials with low variance, the blue group represents trials with moderate variance, and the green and purple groups represent trials with high variance.
B The red group represents trials with low variance, the blue group represents trials with moderate variance in A, B , and the green group represents trials with high variance in A, B. C The red group represents trials with low variance, and the blue group represents trials with high variance.
D The red group represents trials with low variance, the blue group represents trials with positive values for PC2, the green group represents trials with negative values for PC1 or PC2, and the purple group represents trials with positive values for PC1.
Interestingly, results reported by Aboonabi et al. From this observation and the differences between prediabetic and diabetic cohorts, it can be inferred that ACN supplementation may be more useful in critical health conditions where the inflammatory response is exacerbated.
The same PCA analyses for the whole group and the Medox ® group were done for the subset of CTs in which sources of uncharacterized or only partially characterized ACNs were used. Two main factors described PCA in Figure 4C blue group shows that results from five CTs were apart from the most prominent cluster around the plot origin 46 , 56 , 64 , 69 , When dosing data were not included in the analysis Figure 4D , none of the non-clustered trials was apart from the main cluster; instead, trials by Chan et al.
This result, in contrast with that obtained from the Medox ® subset, suggests that no significant correlations exist between concentrations used for uncharacterized sources and their effects on measured metabolic markers. Several observations can be made by analyzing the outliers in Figure 4D.
A CT conducted by Basu et al. Similarly, Chai et al. Although data regarding oxLDL and MDA levels grouped both trials in PCA, no similarities were found in ACN composition [primarily cyanidin for Chai et al.
Besides, Chai et al. From studies that found similarly modified CRP levels to the trial by Chai et al. Although Chew et al. CT conducted by Do Rosario et al. Regarding selected cohorts, Do Rosario et al. Although Do Rosario et al. Both studies used similar daily doses with slightly different compositions Table 2.
Queen garnet plum contains mainly cyanidin glucoside and ruthenoside, while red raspberries have predominantly cyanidin and delphinidin glucosides. As the main component in both studies that reported decreased TNFα levels, cyanidin could reflect a similar mechanism in older adults and subjects with obesity.
Do Rosario et al. This fact suggests that the correlation between cyanidin content and CRP levels in Chai et al. and Chew et al. studies is complex 55 , Recently, Do Rosario et al.
These contrasting results may reflect the issue discussed in a meta-analysis by Sangsefidi et al. Our analysis suggests that CRP levels should be determined alongside other cytokines to effectively describe inflammation in future research addressing the ACN effect.
Triacyl glyceride levels after ACN interventions for studies by Soltani et al. Soltani et al. intervened in hyperlipidemic subjects; therefore, bigger changes in lipid markers reinforce the observation that ACN interventions substantially modulate several markers in subjects with increased baseline levels.
The CT conducted by Kianbakht et al. Conversely, Chan et al. Both studies reported the total anthocyanins used, but the composition was investigated in the literature and databases Table 2. From this comparison, it may be implied that ACNs with low dosing through long periods result in better outcomes than shorter periods with high doses.
In addition, ACN bioavailability obtained with a unique high dose was found higher than the same dose divided throughout the day Such difference may be explained if metabolites derived from intact ACNs show effects and health benefits, thus justifying future detailed studies addressing the effects of single ACNs and their metabolites.
A comparison between studies testing raspberries revealed that even though the ACN dose was almost fold higher in the study by Schell et al. Jeong et al.
reported quantity of the used fruits, but ACN doses Discrepancies may be due to variability in parameters such as specific cultivar, zone, and ripening year, which are not considered in Table 2. Differences could also be due to an increased bioavailability of the ACNs present in the capsules used by Jeong et al.
Specifically, the black raspberry extract used by Jeong et al. and Schell et al. regarding IL-6 and TNFα serum levels 72 , In those studies, daily cyanidin doses were similar study compared to Schell et al.
Since the rest of the compounds were scarce in the trial by Li et al. Furthermore, it is important to note the treatment time because the lowest TNFα level was achieved in only 4 weeks 72 with a non-purified source of ACNs compared with 24 weeks of Medox ® treatment In both cases, the patients presented diabetes, but Schell et al.
subjects also presented obesity, possibly indicating ACNs are more relevant for TNFα levels in subjects with obesity. Results from further studies should be used to contrast these data and improve our understanding of specific markers that better display the anti-inflammatory properties of ACNs.
However, more studies should be conducted to better examine the anti-inflammatory effect and other mechanisms of action of ACNs. From the observed studies with more increased markers Figure 2 , only the CT reported by Lehtonen et al.
Three of all the studies found that ACN intervention changed serum insulin concentration, and Lehtonen et al. Therefore, the augmented marker only had a small influence on the overall data.
Nevertheless, it is important to notice that only six studies among the 49 included reported insulin levels. The small representation of insulin levels supports the need for this determination in future studies investigating obesity-related inflammation to clarify involved mechanisms in the ACN effect.
Postprandial studies in which ACN ability to modify changes produced by ingestion of meals were not included in PCAs as they evaluate short-term ACN effect maximum 1 week.
However, the information provided by these CTs in which inflammatory markers were evaluated resembles, to some extent, the results obtained with more prolonged treatments.
The CTs have evaluated the ACN effect after consumption of meals high in fat 25 , 77 , 97 — 99 or high in fat and carbohydrates — , and also have evaluated postprandial effects after consuming only ACN-rich meals , Particularly, the high-fat meal challenge studies have been recently reviewed , and protective effects on oxidative stress and antioxidant status, triacylglycerol and total cholesterol concentrations, vascular endothelial function, and inflammatory biomarkers have been identified after ACN consumption.
Furthermore, positive changes regarding vascular stiffness 98 , insulin sensitivity , oxLDL , malondialdehyde 99 , and expression of pro-inflammatory and antioxidant genes in peripheral blood mononuclear cells 25 among others have been found.
A deep analysis of metabolites reported in the postprandial studies and the interaction of ACNs and such metabolites with gut microbiota is out of the scope of this review. However, a detailed discussion about gut microbiota interactions with ACNs and their metabolites from animal studies has already been published , On the other hand, studies discussing bioavailability, as those mentioned in Section 3, and analysis of reported metabolites 25 , , , should be addressed in future works.
To get a better understanding of individual ACN impact, studies that evaluated the effect of single ACNs were reviewed — Among the analyzed studies, pelargonidin, malvidin, delphinidin, and cyanidin produced the most remarkable changes for inflammation- and obesity-related markers , , , , — Those works with the highest variance used aglycones anthocyanidins even though 9 of the 26 entries tested anthocyanins.
Concentrations used in these studies were 30 μM for pelargonidin in LPS-treated HUVEC cells , ; 10, 50, and μM for delphinidin in SKOV3 cells, neonatal rat cardiomyocytes or HCT cells, respectively , , ; μM for malvidin in LPS-treated human peripheral mononuclear cells ; and μM for cyanidin in LPS-treated Caco-2 cells Gan et al.
also determined the efficacy of cyanidin and cyanidin glucoside on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Notably, in both models, they found that the effect of cyanidin and cyanidin glucoside was not statistically different. This last observation may confirm the hypothesis that anthocyanidins and anthocyanin glucosides produce similar results.
Since we did not find information to make other comparisons between anthocyanidins and their corresponding glucosides, future experimentation would shed some light on this matter.
Moreover, VEGF can be diminished by delphinidin or delphinidin glucoside, and the concentrations reported for this effect are quite dissimilar from 40 to μM , Of particular interest are the findings by Jia et al. Finally, classical inflammation markers such as TNFα, IL-1β, IL-6, and NFκB were mainly measured in cyanidin-treated models, proving to be an excellent candidate for preventing inflammation , , — Although pelargonidin has also been shown to prevent LPS-induced inflammation markers in HUVEC cells, further studies are required to fully understand how this prevention occurs Although comparisons made in this review are subject to many sources of variation, our data showed that pelargonidin might have promising characteristics individually or synergistically with cyanidin.
Furthermore, the comparison made in Section 3. However, the low potency of ACNs in general and specifically pelargonidin has been associated with instability in the human physiological environment, and some studies have attempted to develop delivery strategies to improve pelargonidin bioavailability Therefore, encapsulation might be an alternative to deliver ACNs to exert their beneficial effects effectively.
On the other hand, cyanidin is the most abundant ACN in several fruit and vegetable sources; for this reason, it has been widely studied.
However, few studies have compared the potency of individual ACNs , , , , raising the question of whether compounds other than cyanidin could also be helpful for specific biological activities. From our search for the last 5 years of studies on single ACNs, seven of the entries tried a cyanidin-based compound, seven a delphinidin-based compound, three a pelargonidin-based compound, two a malvidin-based compound, and none of them a peonidin-based compound.
Structure—activity relationships have explored the influence of glycosylation on the biological activity of ACNs and compared their antioxidant activity , However, further explorations and comparisons for individual compounds linking anti-inflammatory and obesity-related biological activities are needed to better understand their relative efficacies.
Various studies have addressed whether ACNs have specific molecular targets regarding chemical structure. For instance, through docking-based virtual screening, Liu et al. Cyanidin binding to this site inhibits ILA-induced gene expression in human and mouse cells by inhibiting the ILRA interaction with the ILA interleukin.
Furthermore, they showed that cyanidin inhibits ILA-dependent skin hyperplasia and attenuates airway inflammation in mouse models of steroid-resistant and severe asthma. In this study, pelargonidin O -glucoside and delphinidin O -glucoside were also shown to interact with PPAR ligand binding domains.
Cyanidin O -arabinoside, cyanidin O -galactoside, peonidin O -arabinoside, and peonidin O -galactoside were also shown to interact with and inhibit pancreatic lipase ; from them, cyanidin O -arabinoside was shown to impact significantly secondary structures of the enzyme.
Finally, the generic ACN core structure without substituents was shown to interact with 3-hydroxymethylglutaryl coenzyme A HMG-CoA reductase and acyl-CoA cholesterol acyltransferase ACAT proteins through molecular docking From all the molecular targets and pathways discussed in this review, selected more representative associations with single ACNs are shown in Figure 5.
Further studies on single ACNs or their metabolites should corroborate or modify these suggestions. Figure 5. Graphic depiction of some beneficial effects and molecular targets reported for flavonoids and anthocyanins. Single anthocyanins likely correlated with specific molecular targets are shown.
Adapted from Azzini et al. Knowing the ACN profile composition of matrices used in CT provides valuable information to partially elucidate individual ACN mechanisms of action.
This information would allow us to design food formulations rich in effective bioactive compounds or to select species and cultivars with optimal composition for specific diseases and bioactivities. The ACN bioavailability was reported to be higher for a unique dose than for the same dose divided throughout the day.
However, more marked effects were observed in CTs that used low doses over long periods and in cohorts with higher baselines for most of the studied markers, coinciding with advanced pathological features.
From our bioavailability and principal components analyses, we found that delphinidin has been shown to reach the highest plasma concentrations and consistently have a significant dose-dependent correlation with HDL levels. From our analysis of pure single anthocyanins studies, pelargonidin showed promising potency and molecular target identification results.
Therefore, we propose that the next steps in ACN research should focus on standardizing doses, identifying individual compounds, and developing delivery strategies to cope with ACN degradation. To better understand mechanisms of action ruling ACN bioactivities, investigating ACN-derived metabolites is also a promising research area.
JF-M: Conceptualization, Data curation, Investigation, Methodology, Visualization, Writing—original draft. AD-U: Investigation, Writing—original draft. This manuscript was supported by the Institute for Obesity Research -Tecnologico de Monterrey seed funding and grant IIORC6-T3-E and the Young Investigator Award on Food Science and Technology from the Mexican Academy of Sciences received by DL-V.
The authors acknowledge the support provided by the School of Medicine and Health Sciences and the School of Engineering and Sciences - Tecnologico de Monterrey. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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Eur J Nutr. Moreover, anthocyanidins are more unstable in cell culture medium, so they are likely converted to other degradation products that may, in turn, be responsible for any observed anti-inflammatory effect. Conversely, anthocyanins are more stable and thus contribute directly to the observed anti-inflammatory effects.
For example, when Triebel et al. Peonidinglycosides were active only as glucose conjugates, while malvidinglucoside, malvidingalactoside, and petunidinglucoside had no significant effect on any of the markers. Another question that requires further investigation is the comparative anti-inflammatory effect of anthocyanins and other phenolic compounds.
Most phenolic compounds exert antioxidant effects; thus, the relevant question is whether anthocyanins exert a stronger anti-inflammatory effect than other phenolics with comparable antioxidant strength.
Data in this regard are very limited. Thus, there is evidence that different phenolics exert different degrees of anti-inflammatory activities, and since there is a paucity of studies in this area, a better understanding of such differences would be particularly useful. The major limitation with cell culture studies is that, in vivo, anthocyanins are metabolized rather quickly to other compounds, such as protocatechuic acid.
In the body proper, the major metabolic effects of anthocyanin consumption are likely due to anthocyanin metabolites, and not to anthocyanins themselves parent compounds. When Min et al. The same result was also observed in vivo: protocatechuic acid was the strongest inhibitor of TNF-α and PGE 2 concentrations, of COX-2 expression, and of NF-κB activation in mice air pouch exudates following oral administration of C3G or its metabolites for 3 days.
A possible strategy to address this problem in cell culture studies is to expose cells to the serum of humans or animals who have previously consumed anthocyanins instead of directly exposing them to purified anthocyanins. As far as can be determined, no studies investigating anthocyanins have been conducted utilizing this strategy.
In conclusion, anthocyanins have been consistently shown to have anti-inflammatory effects, as evidenced by their ability to 1 lower the concentration and expression of proinflammatory mediators while increasing that of anti-inflammatory molecules, 2 attenuate iNOS activity and thus nitric oxide overexpression, and 3 reduce COX-2 activity and thus PGE 2 expression.
As for their mechanisms of action, most of the evidence points to involvement of the NF-κB pathway; anthocyanins have been consistently shown both in vitro and in vivo to inhibit the translocation and activation of NF-κB and the phosphorylation of its upstream inhibitor.
Since NF-κB is a redox-sensitive transcription factor, this effect of anthocyanins is most likely attributable to their strong antioxidant activity. Evidence also points to the involvement of other pathways that are at least partially involved in the inflammatory response, such as the phosphorylation of MAPKs or the AP Some authors have suggested a direct binding of anthocyanins to several proteins in these pathways, such as Fyn kinase.
Future research is needed to improve current understanding of the most biologically effective dose of anthocyanins, the specific activity of single anthocyanins or anthocyanidins, the differential effect of other phenolics for which an anti-inflammatory effect has also been reported, and the extent to which the observed biological activities are exerted by anthocyanins themselves parent compounds or their metabolites.
This work was partially supported by the Wild Blueberry Association of North America and by Hatch Grant no. ME from the United States Department of Agriculture, National Institute of Food and Agriculture.
The article is publication no. Declaration of interest. The authors have no relevant interests to declare. Samad F Ruf W. Inflammation, obesity, and thrombosis. Google Scholar.
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Anthocyanins ACNs are phytochemicals Anthocyxnins numerous bioactivities, e. Health benefits from Tart cranberry recipes ACN-rich foods, Belly fat burner workout, and supplements have been studied Anti-infkammatory clinical anti-nflammatory CT. However, the individual effect of Type diabetes technology ACNs and their correlation with doses and specific bioactivities or molecular targets have not been thoroughly analyzed. This review shows a recompilation of single anthocyanins composition and concentrations used in CT, conducted to investigate the effect of these anti-inflammatory derivatives in obese condition. Single anthocyanin doses with changes in the levels of frequently monitored markers were correlated.a Programa de Tart cranberry recipes Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, Antl-inflammatory, Brazil. b Departamento de Biociências, Anthochanins de Nutrição e Omega- rich snacks Endócrina LaNFE ; Universidade Federal de São Paulo, Santos, Brazil E-mail: anti-infammatory gmail.
c School Anthocyyanins Tart cranberry recipes Fueling for peak athletic performance and Health, Gluten-Free Nut Flours of Medicine, University Anfi-inflammatory Southampton, Southampton SO16 6YD, UK.
d Andd of Nutrition, Faculty of Pharmacy, University of Valparaíso, Valparaíso, Chile. e NIHR Southampton Anti-inflammstory Research Centre, University Antiinflammatory Southampton NHS Foundation Trust and Anthocywnins of Southampton, Southampton SO16 anti-inflamjatory, UK.
Monocyte Tart cranberry recipes and activation Anthochanins macrophages anti-onflammatory essential for homeostasis but are Anthocyains related to Anthocyanins and anti-inflammatory effects development and progression of cardiometabolic diseases.
Anto-inflammatory management of inflammation with dietary components has Fasting and metabolism widely Metformin and blood glucose monitoring. Two components that Anthocyanins and anti-inflammatory effects influence inflammation Anthocyanis unsaturated fatty anc such Quercetin and liver health oleic anti-inflanmatory OA; cis-9 and antioxidant compounds like anti-innflammatory.
Molecular Annthocyanins metabolic effects Anthocyanins and athletic performance such bioactive compounds are usually investigated in Cholesterol level impact, whereas they may be present effects combination Ahd foods or the diet.
Considering this, we aimed to anti-inflakmatory the effects of Dffects and anti-inf,ammatory anthocyanin keracyanin Antyocyanins alone and in combination effedts toll-like receptor-mediated inflammatory Anthocynains in monocytes and Tart cranberry recipes.
Antti-inflammatory this, Effect macrophages efects monocytes were Anthocyyanins to 3 treatments: OA, AC, or the combination OAAC and then stimulated with lipopolysaccharide. Inflammation-related gene expression and protein concentrations of IL-1β, TNF-α, IL-6, MCP-1, and IL were assessed.
Also, NFκBp65, IκBα, and PPAR-γ protein expression were determined. OA, AC, and OAAC decreased pNFκBp65, PPARγ, IκBα, TNF-α, IL-1β, IL-6, and MCP-1 and increased IL MCP-1 protein expression was lower with OAAC than with either OA and AC alone.
Compared to control, OAAC decreased mRNA for TLR4, IκKα, IκBα, NFκB1, MCP-1, TNF-α, IL-6, and IL-1β more than OA or AC did alone. Also, IL mRNA was increased by OAAC compared with control, OA, and AC. In summary, OA and AC have anti-inflammatory effects individually but their combination OAAC exerts a greater effect.
Santamarina, L. Pisani, E. Baker, A. Marat, C. Valenzuela, E. Miles and P. Calder, Food Funct. To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.
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Anti-inflammatory effects of oleic acid and the anthocyanin keracyanin alone and in combination: effects on monocyte and macrophage responses and the NF-κB pathway A.
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: Anthocyanins and anti-inflammatory effects| Human Verification | Effecta Anthocyanins and anti-inflammatory effects, — When anti-ihflammatory data were not included in the ahti-inflammatory Figure 4Danto-inflammatory of the non-clustered Tart cranberry recipes was apart from the Body composition evaluation method cluster; anti-knflammatory, trials by Chan et al. The protection and especially the controlled release of various organic molecules is achieved almost exclusively by means of encapsulated compounds. That contributes to the partial explanation of the variability of maximum anthocyanin concentration in plasma in studies using the same anthocyanin source; for instance, in a study by Marques et al. Effects of the ethanol extract of black mulberry Morus nigra L. |
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Keywords: anthocyanins, biodisponibility, neuroprotective, cardioprotective, antiobesity, antidiabetic, antioxidant, anticancer. Citation: Salehi B, Sharifi-Rad J, Cappellini F, Reiner Ž, Zorzan D, Imran M, Sener B, Kilic M, El-Shazly M, Fahmy NM, Al-Sayed E, Martorell M, Tonelli C, Petroni K, Docea AO, Calina D and Maroyi A The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action. Received: 29 May ; Accepted: 05 August ; Published: 26 August Copyright © Salehi, Sharifi-Rad, Cappellini, Reiner, Zorzan, Imran, Sener, Kilic, El-Shazly, Fahmy, Al-Sayed, Martorell, Tonelli, Petroni, Docea, Calina and Maroyi. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. sharifirad gmail. com ; Miquel Martorell, mmartorell udec. cl ; Katia Petroni, katia. petroni unimi. it ; Daniela Calina, calinadaniela gmail. com ; Alfred Maroyi, amaroyi ufh. In addition, ACN bioavailability obtained with a unique high dose was found higher than the same dose divided throughout the day Such difference may be explained if metabolites derived from intact ACNs show effects and health benefits, thus justifying future detailed studies addressing the effects of single ACNs and their metabolites. A comparison between studies testing raspberries revealed that even though the ACN dose was almost fold higher in the study by Schell et al. Jeong et al. reported quantity of the used fruits, but ACN doses Discrepancies may be due to variability in parameters such as specific cultivar, zone, and ripening year, which are not considered in Table 2. Differences could also be due to an increased bioavailability of the ACNs present in the capsules used by Jeong et al. Specifically, the black raspberry extract used by Jeong et al. and Schell et al. regarding IL-6 and TNFα serum levels 72 , In those studies, daily cyanidin doses were similar study compared to Schell et al. Since the rest of the compounds were scarce in the trial by Li et al. Furthermore, it is important to note the treatment time because the lowest TNFα level was achieved in only 4 weeks 72 with a non-purified source of ACNs compared with 24 weeks of Medox ® treatment In both cases, the patients presented diabetes, but Schell et al. subjects also presented obesity, possibly indicating ACNs are more relevant for TNFα levels in subjects with obesity. Results from further studies should be used to contrast these data and improve our understanding of specific markers that better display the anti-inflammatory properties of ACNs. However, more studies should be conducted to better examine the anti-inflammatory effect and other mechanisms of action of ACNs. From the observed studies with more increased markers Figure 2 , only the CT reported by Lehtonen et al. Three of all the studies found that ACN intervention changed serum insulin concentration, and Lehtonen et al. Therefore, the augmented marker only had a small influence on the overall data. Nevertheless, it is important to notice that only six studies among the 49 included reported insulin levels. The small representation of insulin levels supports the need for this determination in future studies investigating obesity-related inflammation to clarify involved mechanisms in the ACN effect. Postprandial studies in which ACN ability to modify changes produced by ingestion of meals were not included in PCAs as they evaluate short-term ACN effect maximum 1 week. However, the information provided by these CTs in which inflammatory markers were evaluated resembles, to some extent, the results obtained with more prolonged treatments. The CTs have evaluated the ACN effect after consumption of meals high in fat 25 , 77 , 97 — 99 or high in fat and carbohydrates — , and also have evaluated postprandial effects after consuming only ACN-rich meals , Particularly, the high-fat meal challenge studies have been recently reviewed , and protective effects on oxidative stress and antioxidant status, triacylglycerol and total cholesterol concentrations, vascular endothelial function, and inflammatory biomarkers have been identified after ACN consumption. Furthermore, positive changes regarding vascular stiffness 98 , insulin sensitivity , oxLDL , malondialdehyde 99 , and expression of pro-inflammatory and antioxidant genes in peripheral blood mononuclear cells 25 among others have been found. A deep analysis of metabolites reported in the postprandial studies and the interaction of ACNs and such metabolites with gut microbiota is out of the scope of this review. However, a detailed discussion about gut microbiota interactions with ACNs and their metabolites from animal studies has already been published , On the other hand, studies discussing bioavailability, as those mentioned in Section 3, and analysis of reported metabolites 25 , , , should be addressed in future works. To get a better understanding of individual ACN impact, studies that evaluated the effect of single ACNs were reviewed — Among the analyzed studies, pelargonidin, malvidin, delphinidin, and cyanidin produced the most remarkable changes for inflammation- and obesity-related markers , , , , — Those works with the highest variance used aglycones anthocyanidins even though 9 of the 26 entries tested anthocyanins. Concentrations used in these studies were 30 μM for pelargonidin in LPS-treated HUVEC cells , ; 10, 50, and μM for delphinidin in SKOV3 cells, neonatal rat cardiomyocytes or HCT cells, respectively , , ; μM for malvidin in LPS-treated human peripheral mononuclear cells ; and μM for cyanidin in LPS-treated Caco-2 cells Gan et al. also determined the efficacy of cyanidin and cyanidin glucoside on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Notably, in both models, they found that the effect of cyanidin and cyanidin glucoside was not statistically different. This last observation may confirm the hypothesis that anthocyanidins and anthocyanin glucosides produce similar results. Since we did not find information to make other comparisons between anthocyanidins and their corresponding glucosides, future experimentation would shed some light on this matter. Moreover, VEGF can be diminished by delphinidin or delphinidin glucoside, and the concentrations reported for this effect are quite dissimilar from 40 to μM , Of particular interest are the findings by Jia et al. Finally, classical inflammation markers such as TNFα, IL-1β, IL-6, and NFκB were mainly measured in cyanidin-treated models, proving to be an excellent candidate for preventing inflammation , , — Although pelargonidin has also been shown to prevent LPS-induced inflammation markers in HUVEC cells, further studies are required to fully understand how this prevention occurs Although comparisons made in this review are subject to many sources of variation, our data showed that pelargonidin might have promising characteristics individually or synergistically with cyanidin. Furthermore, the comparison made in Section 3. However, the low potency of ACNs in general and specifically pelargonidin has been associated with instability in the human physiological environment, and some studies have attempted to develop delivery strategies to improve pelargonidin bioavailability Therefore, encapsulation might be an alternative to deliver ACNs to exert their beneficial effects effectively. On the other hand, cyanidin is the most abundant ACN in several fruit and vegetable sources; for this reason, it has been widely studied. However, few studies have compared the potency of individual ACNs , , , , raising the question of whether compounds other than cyanidin could also be helpful for specific biological activities. From our search for the last 5 years of studies on single ACNs, seven of the entries tried a cyanidin-based compound, seven a delphinidin-based compound, three a pelargonidin-based compound, two a malvidin-based compound, and none of them a peonidin-based compound. Structure—activity relationships have explored the influence of glycosylation on the biological activity of ACNs and compared their antioxidant activity , However, further explorations and comparisons for individual compounds linking anti-inflammatory and obesity-related biological activities are needed to better understand their relative efficacies. Various studies have addressed whether ACNs have specific molecular targets regarding chemical structure. For instance, through docking-based virtual screening, Liu et al. Cyanidin binding to this site inhibits ILA-induced gene expression in human and mouse cells by inhibiting the ILRA interaction with the ILA interleukin. Furthermore, they showed that cyanidin inhibits ILA-dependent skin hyperplasia and attenuates airway inflammation in mouse models of steroid-resistant and severe asthma. In this study, pelargonidin O -glucoside and delphinidin O -glucoside were also shown to interact with PPAR ligand binding domains. Cyanidin O -arabinoside, cyanidin O -galactoside, peonidin O -arabinoside, and peonidin O -galactoside were also shown to interact with and inhibit pancreatic lipase ; from them, cyanidin O -arabinoside was shown to impact significantly secondary structures of the enzyme. Finally, the generic ACN core structure without substituents was shown to interact with 3-hydroxymethylglutaryl coenzyme A HMG-CoA reductase and acyl-CoA cholesterol acyltransferase ACAT proteins through molecular docking From all the molecular targets and pathways discussed in this review, selected more representative associations with single ACNs are shown in Figure 5. Further studies on single ACNs or their metabolites should corroborate or modify these suggestions. Figure 5. Graphic depiction of some beneficial effects and molecular targets reported for flavonoids and anthocyanins. Single anthocyanins likely correlated with specific molecular targets are shown. Adapted from Azzini et al. Knowing the ACN profile composition of matrices used in CT provides valuable information to partially elucidate individual ACN mechanisms of action. This information would allow us to design food formulations rich in effective bioactive compounds or to select species and cultivars with optimal composition for specific diseases and bioactivities. The ACN bioavailability was reported to be higher for a unique dose than for the same dose divided throughout the day. However, more marked effects were observed in CTs that used low doses over long periods and in cohorts with higher baselines for most of the studied markers, coinciding with advanced pathological features. From our bioavailability and principal components analyses, we found that delphinidin has been shown to reach the highest plasma concentrations and consistently have a significant dose-dependent correlation with HDL levels. From our analysis of pure single anthocyanins studies, pelargonidin showed promising potency and molecular target identification results. Therefore, we propose that the next steps in ACN research should focus on standardizing doses, identifying individual compounds, and developing delivery strategies to cope with ACN degradation. To better understand mechanisms of action ruling ACN bioactivities, investigating ACN-derived metabolites is also a promising research area. JF-M: Conceptualization, Data curation, Investigation, Methodology, Visualization, Writing—original draft. AD-U: Investigation, Writing—original draft. This manuscript was supported by the Institute for Obesity Research -Tecnologico de Monterrey seed funding and grant IIORC6-T3-E and the Young Investigator Award on Food Science and Technology from the Mexican Academy of Sciences received by DL-V. The authors acknowledge the support provided by the School of Medicine and Health Sciences and the School of Engineering and Sciences - Tecnologico de Monterrey. 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Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. Vinson JA, Demkosky CA, Navarre DA, Smyda MA. High-antioxidant potatoes: acute in vivo antioxidant source and hypotensive agent in humans after supplementation to hypertensive subjects. Xie L, Vance T, Kim B, Lee SG, Caceres C, Wang Y, et al. Aronia berry polyphenol consumption reduces plasma total and low-density lipoprotein cholesterol in former smokers without lowering biomarkers of inflammation and oxidative stress: a randomized controlled trial. Nutr Res. Do Rosario VA, Fitzgerald Z, Broyd S, Paterson A, Roodenrys S, Thomas S, et al. Food anthocyanins decrease concentrations of TNF-α in older adults with mild cognitive impairment: a randomized, controlled, double blind clinical trial. Nutr Metab Cardiovas Dis. Stote KS, Wilson MM, Hallenbeck D, Thomas K, Rourke JM, Sweeney MI, Gottschall-Pass KT, Gosmanov AR. Effect of blueberry consumption on cardiometabolic health parameters in men with type 2 diabetes: an 8-week, double-blind, randomized, placebo-controlled trial. Curr Dev Nutr. Kianbakht S, Abasi B, Hashem Dabaghian F. Improved lipid profile in hyperlipidemic patients taking vaccinium arctostaphylos fruit hydroalcoholic extract: a randomized double-blind placebo-controlled clinical trial. Phytother Res. Aboonabi A, Roselyn R, Meyer IS, Aboonabi A. Anthocyanins reduce inflammation and improve glucose and lipid metabolism associated with inhibiting nuclear factor-kappaB activation and increasing PPAR-γ gene expression in metabolic syndrome subjects. Free Radic Biol Med. Guo Y, Zhang P, Liu Y, Zha L, Ling W, Guo H, et al. A dose-response evaluation of purified anthocyanins on inflammatory and oxidative biomarkers and metabolic risk factors in healthy young adults: a randomized controlled trial. Hassellund SS, Flaa A, Kjeldsen SE, Seljeflot I, Karlsen A, Erlund I, et al. Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men: a double-blind randomized placebo-controlled crossover study. J Hum Hypertens. Karlsen A, Retterstøl L, Laake P, Paur I, Kjølsrud-Bøhn S, Sandvik L, et al. Anthocyanins inhibit nuclear factor-κb activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. Li D, Zhang Y, Liu Y, Sun R, Xia M. Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients. Thompson K, Hosking H, Pederick W, Singh I, Santhakumar AB. The effect of anthocyanin supplementation in modulating platelet function in sedentary population: a randomised, double-blind, placebo-controlled, cross-over trial. Anthocyanin supplementation at different doses improves cholesterol efflux capacity in subjects with dyslipidemia-a randomized controlled trial. Yang L, Qiu Y, Ling W, Liu Z, Yang L, Wang C, et al. Anthocyanins regulate serum adipsin and visfatin in patients with prediabetes or newly diagnosed diabetes: a randomized controlled trial. Yang L, Ling W, Yang Y, Chen Y, Tian Z, Du Z, et al. Role of purified anthocyanins in improving cardiometabolic risk factors in chinese men and women with prediabetes or early untreated diabetes—a randomized controlled trial. Zhang H, Xu Z, Zhao H, Wang X, Pang J, Li Q, et al. Anthocyanin supplementation improves anti-oxidative and anti-inflammatory capacity in a dose—response manner in subjects with dyslipidemia. Zhang PW, Chen FX Li D, Ling WH, Guo HH. A CONSORT-compliant, randomized, double-blind, placebo-controlled pilot trial of purified anthocyanin in patients with nonalcoholic fatty liver disease. Zhang X, Zhu Y, Song F, Yao Y, Ya F, Li D, et al. Effects of purified anthocyanin supplementation on platelet chemokines in hypocholesterolemic individuals: a randomized controlled trial. Nutr Metab. Zhu X, Lin X, Zhang P, Liu Y, Ling W, Guo H, et al. Upregulated NLRP3 inflammasome activation is attenuated by anthocyanins in patients with nonalcoholic fatty liver disease: a case-control and an intervention study. Clin Res Hepatol Gastroenterol. Zhu Y, Ling W, Guo H, Song F, Ye Q, Zou T, et al. Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia: a randomized controlled trial. Zhu Y, Xia M, Yang Y, Liu F, Li Z, Hao Y, et al. Purified anthocyanin supplementation improves endothelial function via NO-CGMP activation in hypercholesterolemic individuals. Clin Chem. Zhu Y, Huang X, Zhang Y, Wang Y, Liu Y, Sun R, et al. Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia. J Clin Endocrinol Metab. Sangsefidi ZS, Hasanizadeh S, Hosseinzadeh M. Effect of purified anthocyanins or anthocyanin-rich extracts on C-reactive protein levels: a systematic review and meta-analysis of randomised clinical trials. Velliquette RA, Grann K, Missler SR, Patterson J, Hu C, Gellenbeck KW, et al. |
| What Is Anthocyanin? Foods List, Benefits, and More | Jump to main content. Jump to site search. You do not have JavaScript enabled. Please enable JavaScript to access the full features of the site or access our non-JavaScript page. Issue 17, Aline B. Santamarina , a Luciana P. Baker , c Andreea D. Marat , c Carina A. Valenzuela , cd Elizabeth A. Miles c and Philip C. Calder ce. You have access to this article. Please wait while we load your content Something went wrong. Try again? Cited by. Download options Please wait Supplementary information PDF K. Article type Paper. Submitted 26 Apr Accepted 24 Jun First published 25 Jun For example, when Triebel et al. Peonidinglycosides were active only as glucose conjugates, while malvidinglucoside, malvidingalactoside, and petunidinglucoside had no significant effect on any of the markers. Another question that requires further investigation is the comparative anti-inflammatory effect of anthocyanins and other phenolic compounds. Most phenolic compounds exert antioxidant effects; thus, the relevant question is whether anthocyanins exert a stronger anti-inflammatory effect than other phenolics with comparable antioxidant strength. Data in this regard are very limited. Thus, there is evidence that different phenolics exert different degrees of anti-inflammatory activities, and since there is a paucity of studies in this area, a better understanding of such differences would be particularly useful. The major limitation with cell culture studies is that, in vivo, anthocyanins are metabolized rather quickly to other compounds, such as protocatechuic acid. In the body proper, the major metabolic effects of anthocyanin consumption are likely due to anthocyanin metabolites, and not to anthocyanins themselves parent compounds. When Min et al. The same result was also observed in vivo: protocatechuic acid was the strongest inhibitor of TNF-α and PGE 2 concentrations, of COX-2 expression, and of NF-κB activation in mice air pouch exudates following oral administration of C3G or its metabolites for 3 days. A possible strategy to address this problem in cell culture studies is to expose cells to the serum of humans or animals who have previously consumed anthocyanins instead of directly exposing them to purified anthocyanins. As far as can be determined, no studies investigating anthocyanins have been conducted utilizing this strategy. In conclusion, anthocyanins have been consistently shown to have anti-inflammatory effects, as evidenced by their ability to 1 lower the concentration and expression of proinflammatory mediators while increasing that of anti-inflammatory molecules, 2 attenuate iNOS activity and thus nitric oxide overexpression, and 3 reduce COX-2 activity and thus PGE 2 expression. As for their mechanisms of action, most of the evidence points to involvement of the NF-κB pathway; anthocyanins have been consistently shown both in vitro and in vivo to inhibit the translocation and activation of NF-κB and the phosphorylation of its upstream inhibitor. Since NF-κB is a redox-sensitive transcription factor, this effect of anthocyanins is most likely attributable to their strong antioxidant activity. Evidence also points to the involvement of other pathways that are at least partially involved in the inflammatory response, such as the phosphorylation of MAPKs or the AP Some authors have suggested a direct binding of anthocyanins to several proteins in these pathways, such as Fyn kinase. Future research is needed to improve current understanding of the most biologically effective dose of anthocyanins, the specific activity of single anthocyanins or anthocyanidins, the differential effect of other phenolics for which an anti-inflammatory effect has also been reported, and the extent to which the observed biological activities are exerted by anthocyanins themselves parent compounds or their metabolites. This work was partially supported by the Wild Blueberry Association of North America and by Hatch Grant no. ME from the United States Department of Agriculture, National Institute of Food and Agriculture. The article is publication no. Declaration of interest. The authors have no relevant interests to declare. Samad F Ruf W. Inflammation, obesity, and thrombosis. Google Scholar. Makki K Froguel P Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. doi: Lafontan M. Adipose tissue and adipocyte dysregulation. Diabetes Metab. Jin C Flavell RA. Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol. Lee H Lee IS Choue R. Obesity, inflammation and diet. Pediatr Gastroenterol Hepatol Nutr. Dai J Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Crozier A Jaganath IB Clifford MN. Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep. Veitch NC Grayer RJ. Flavonoids and their glycosides, including anthocyanins. Andersen OM Jordheim M. The anthocyanins. In: Andersen OM Markham KR , eds. Flavonoids: Chemistry, Biochemistry, And Applications. New York, NY : CRC Press ; : — Google Preview. Wallace TC. Anthocyanins in cardiovascular disease. Adv Nutr. Klabusay M Kohutova V Coupek P et al. Simultaneous analysis of cytokines concentrations occurring in plasma of healthy blood donors. Med Inflamm. Ng PC Li K Wong RPO et al. Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections. Arch Dis Child Fet Neonat. Van de Voorde J Pauwels B Boydens C et al. Adipocytokines in relation to cardiovascular disease. Kim SM Chung MJ Ha TJ et al. Life Sci. Paixão J Dinis TC Almeida LM. Malvidinglucoside protects endothelial cells up-regulating endothelial NO synthase and inhibiting peroxynitrite-induced NF-kB activation. Chem Biol Interact. Ju JH Yoon HS Park HJ et al. Anti-obesity and antioxidative effects of purple sweet potato extract in 3T3-L1 adipocytes in vitro. J Med Food. Poulose SM Fisher DR Larson J et al. Anthocyanin-rich açai Euterpe oleracea Mart. fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells. J Agric Food Chem. Triebel S Trieu HL Richling E. Modulation of inflammatory gene expression by a bilberry Vaccinium myrtillus L. extract and single anthocyanins considering their limited stability under cell culture conditions. Lee SG Kim B Yang Y et al. Berry anthocyanins suppress the expression and secretin of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism. J Nutr Biochem. Min SW Ryu SN Kim DH. Anti-inflammatory effects of black rice, cyanidinO-beta-D-glycoside, and its metabolites, cyanidin and protocatechuic acid. Int Immunopharmacol. Zdarilová A Rajnochová Svobodová A Chytilová K et al. Polyphenolic fraction of Lonicera caerulea L. fruits reduces oxidative stress and inflammatory markers induced by lipopolysaccharide in gingival fibroblasts. Food Chem Toxicol. Zhu Y Ling W Guo H et al. Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia: a randomized controlled trial. Nutr Metab Cardiovasc Dis. Zhang Y Lian F Zhu Y et al. Cyanidin O -beta-glucoside inhibits LPS-induced expression of inflammatory mediators through decreasing IκBα phosphorylation in THP-1 cells. Inflamm Res. Tsuda T Ueno Y Yoshikawa T et al. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem Pharmacol. Speciale A Canali R Chirafisi J et al. Cyanidin O -glucoside protection against TNF-α-induced endothelial dysfunction: involvement of nuclear factor-κB signaling. Li J Lim SS Lee JY et al. Purple corn anthocyanins dampened high-glucose-induced mesangial fibrosis and inflammation: possible renoprotective role in diabetic nephropathy. Nizamutdinova IT Kim YM Chung JI et al. Anthocyanins from black soybean seed coats preferentially inhibit TNF-α-mediated induction of VCAM-1 over ICAM-1 through the regulation of GATAs and IRF Niederberger E Geisslinger G. Proteomics and NF-κB: an update. Expert Rev Proteomics. Hoesel B Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. Structural basis of signal transduction in the TNF receptor superfamily. Adv Immunol. Kim JM Kim KM Park EH et al. Anthocyanins from black soybean inhibit Helicobacter pylori -induced inflammation in human gastric epithelial AGS cells. Microbiol Immunol. Tsoyi K Park HB Kim YM et al. Pergola C Rossi A Dugo P et al. Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. Nitric Oxide. Hecht SS Huang C Stoner GD et al. Identification of cyanidin glycosides as constituents of freeze-dried black raspberries which inhibit anti-benzo[a]pyrene-7,8-diol-9,epoxide induced NFκB and AP-1 activity. Liu HS Chen YH Hung PF et al. Am J Physiol Endocrinol Metab. Afaq F Malik A Syed D et al. Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes. Photochem Photobiol. Lim TG Kwon JY Kim J et al. Cyanidinglucoside suppresses B[a]PDE-induced cyclooxygenase-2 expression by directly inhibiting Fyn kinase activity. Chen PN Kuo WH Chiang CL et al. Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression. Red, purple , and blue fruits and vegetables typically boast the highest amount of anthocyanins. The following foods contain the most anthocyanins per 3. Other anthocyanin-rich foods include purple corn, pomegranate , eggplant, black carrots, red cabbage, and purple cauliflower, which may provide anywhere from a few to — mg per 3. The anthocyanin content of these foods varies so widely because growing area, climate, season, light exposure, harvest time, and storing temperature all affect antioxidant content 6. Amounts may also depend on whether foods are fresh, frozen, or dried — the last of which typically has the lowest anthocyanin content 7. To maximize your intake of anthocyanins from these foods, eat them raw and at their ripest if possible. Red, blue, and purple produce is generally the richest in anthocyanins. Raw, ripe varieties tend to have the highest amounts due to variability in this nutrient. Anthocyanins have antioxidant properties, meaning that they fight damaging compounds called free radicals. When free radicals accumulate in your body, they cause oxidative stress. In turn, this oxidative stress leads to inflammation and may increase your risk of chronic ailments, such as cancer and heart disease 3 , 4. Anthocyanins are also believed to help reduce inflammation 3 , 4. In a week study in people with high cholesterol, supplementing with mg of anthocyanins twice per day significantly reduced markers of inflammation 8. Plus, in a 4-week study, people with and without overweight or obesity who took mg of anthocyanins daily had significantly lower blood markers of inflammation 9. Additionally, one study suggests that these compounds may help reduce inflammation and pain in people with inflammatory arthritis Since chronic inflammation may cause several chronic conditions, including type 2 diabetes and heart disease , regularly eating anthocyanin-rich foods may help protect you from these Regularly eating foods that are rich in anthocyanins may safeguard against type 2 diabetes. Furthermore, adding as little as 7. To put this into perspective, 7. Both of these benefits may reduce your risk of type 2 diabetes However, other studies find no effect 11 , However, anthocyanins are classified as flavonoids, a group of antioxidants believed to have strong cancer-fighting abilities 14 , These alternative treatments are less aggressive than conventional cancer drugs and appear to be especially helpful when combined with chemotherapy Like other flavonoids, anthocyanins may fight free radicals, lower inflammation, and prevent DNA damage — all factors which may help prevent tumor formation Anthocyanins may also help prevent cancer cells from multiplying and spreading. For instance, one test-tube study suggests that they may activate certain genes that kill prostate cancer cells Anthocyanins also appear effective at preventing leukemia and ovarian cancer cells from spreading. Keep in mind that most studies have been done exclusively in test tubes or animals. Therefore, more research involving humans — in addition to more anthocyanin-specific research — is needed. In a week study, people who drank 6. In another, those who drank 10 ounces mL of anthocyanin-rich plum juice daily saw a significant drop in blood pressure that remained 6 hours later. While participants from all age groups experienced this drop, it was most significant in older adults In addition, anthocyanins may lower triglyceride and LDL bad cholesterol levels while increasing HDL good cholesterol levels 6 , 22 , 23 , Anthocyanins may also benefit your brain. A recent review of randomized control trials — the gold standard in scientific research — suggests that these compounds boost your memory, attention, and brain processing speed For instance, a review of seven short- and long-term studies claims that diets rich in anthocyanins may improve verbal learning and memory in children, adults, and older adults with cognitive impairment Another review of 21 long-term studies suggests that supplementing with flavonoids improves attention, memory , and brain processing speed in healthy adults — as well as memory in children and older adults Anthocyanin-rich cherry juice appears to offer similar benefits. In a week study, older adults with mild to moderate dementia saw significant improvements in verbal fluency and short- and long-term memory after drinking 6. The strong antioxidant and anti-inflammatory potential of anthocyanins may benefit your brain and heart, as well as reduce your risk of type 2 diabetes and certain cancers. |
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Mulberry ethanol extract attenuates hepatic steatosis and insulin resistance in high-fat diet-fed mice. Speciale, A. Nutritional antioxidants and adaptive cell responses: an update. CyanidinO-glucoside counters the response to TNF-alpha of endothelial cells by activating Nrf2 pathway. Stewart, C. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Strathearn, K. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinsons disease. Subhramanyam, C. Microglia-mediated neuroinflammation in neurodegenerative diseases. Cell Dev. Sui, X. Impact of Food Processing on Anthocyanins New York: Springer. Sun, H. Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS. Prostaglandins in action indispensable roles of cyclooxygenase-1 and -2 in endothelium-dependent contractions. Adv Pharmacol. 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Anthocyanins from purple sweet potato attenuate dimethylnitrosamine-induced liver injury in rats by inducing Nrf2-mediated antioxidant enzymes and reducing COX-2 and iNOS expression. Shan Q Lu J Zheng Y Li J et al. Purple sweet potato color ameliorates cognition deficits and attenuates oxidative damage and inflammation in aging mouse brain induced by D-galactose. J Biomed Biotechnol. Protective effects of bilberry Vaccinium myrtillus L. extract against endotoxin-induced uveitis in mice. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Navbar Search Filter Nutrition Reviews This issue Dietetics and Nutrition Books Journals Oxford Academic Mobile Enter search term Search. Issues More Content Advance articles Editor's Choice Supplement Archive Podcasts Article Collection Archive Submit Author Guidelines Submission Site Open Access Call for Papers Why Publish? Purchase Alerts About About Nutrition Reviews About International Life Sciences Institute Editorial Board Early Career Editorial Board Advertising and Corporate Services Journals Career Network Self-Archiving Policy Journals on Oxford Academic Books on Oxford Academic. Purchase Alerts About About Nutrition Reviews About International Life Sciences Institute Editorial Board Early Career Editorial Board Advertising and Corporate Services Journals Career Network Self-Archiving Policy Close Navbar Search Filter Nutrition Reviews This issue Dietetics and Nutrition Books Journals Oxford Academic Enter search term Search. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. IN VITRO EVIDENCE. IN VIVO EVIDENCE. Journal Article. Anti-inflammatory effect of anthocyanins via modulation of nuclear factor-κB and mitogen-activated protein kinase signaling cascades. Stefano Vendrame , Stefano Vendrame. Vendrame and D. Klimis-Zacas are with the Department of Food Science and Human Nutrition, University of Maine, Orono, Maine, USA. Oxford Academic. Dorothy Klimis-Zacas. PDF Split View Views. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter Nutrition Reviews This issue Dietetics and Nutrition Books Journals Oxford Academic Enter search term Search. Abstract Anthocyanins are a group of bioactive compounds present in plant foods. anthocyanins , activator protein-1 , inflammation , mitogen-activated protein kinases , nuclear factor-κB , signaling pathways. Figure 1. Open in new tab Download slide. Table 1 Summary of observed in vivo effects of anthocyanin on the expression of genes related to inflammation. Upregulated genes. Downregulated genes. Open in new tab. Google Scholar Crossref. Search ADS. Google Scholar Google Preview OpenURL Placeholder Text. Google Scholar OpenURL Placeholder Text. Google Scholar PubMed. OpenURL Placeholder Text. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals. permissions oup. Issue Section:. Download all slides. Views 2, More metrics information. Total Views 2, Email alerts Article activity alert. Advance article alerts. New issue alert. Receive exclusive offers and updates from Oxford Academic. Citing articles via Web of Science Please enable JavaScript to access the full features of the site or access our non-JavaScript page. Issue 17, Aline B. Santamarina , a Luciana P. Baker , c Andreea D. Marat , c Carina A. Valenzuela , cd Elizabeth A. Miles c and Philip C. Calder ce. You have access to this article. Please wait while we load your content Something went wrong. Try again? Cited by. Download options Please wait Supplementary information PDF K. Article type Paper. Submitted 26 Apr Accepted 24 Jun First published 25 Jun Download Citation. Food Funct. Request permissions. |
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