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Obesity is a costly and ongoing health complication in the United States and globally. Bioactive-rich foods, especially those providing polyphenols, represent an emerging and attractive strategy to address this issue. Berry-derived anthocyanins and their metabolites are of particular interest for their bioactive effects, including weight maintenance and protection from metabolic aberrations. Earlier findings from small clinical trials suggest modulation of substrate oxidation and glucose tolerance with mediation of prospective benefits attributable to the gut microbiota, but mixed results suggest appropriate anthocyanin dosing poses a challenge. The objective of this randomized, placebo-controlled study was to determine if anthocyanin-dense elderberry juice (EBJ) reproduces glucoregulatory and substrate oxidation effects observed with other berries and if this is mediated by the gut microbiota. Overweight or obese adults (BMI > 25 kg/m 2 ) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. Each treatment period included 4 days of controlled feeding with a 40% fat diet to allow for comparison of measurements in fecal microbiota, meal tolerance testing (MTT), and indirect calorimetry between test beverages. Eighteen study volunteers completed the study. At the phylum level, EBJ significantly increased Firmicutes and Actinobacteria, and decreased Bacteroidetes. At the genus level, EBJ increased Faecalibacterium , Ruminococcaceae , and Bifidobacterium and decreased Bacteroides and lactic acid-producing bacteria, indicating a positive response to EBJ. Supporting the changes to the microbiota, the EBJ treatment significantly reduced blood glucose following the MTT. Fat oxidation also increased significantly both during the MTT and 30 min of moderate physical activity with the EBJ treatment. Our findings confirm the bioactivity of EBJ-sourced anthocyanins on outcomes related to gut health and obesity. Follow-up investigation is needed to confirm our findings and to test for longer durations.

Persimmon fruit processing-derived waste and by-products, such as peels and pomace, are important sources of dietary fiber and phytochemicals. Revalorizing these by-products could help promote circular nutrition and agricultural sustainability while tackling dietary deficiencies and chronic diseases. In this study, fiber-rich fractions were prepared from the by-products of Sharoni and Brilliant Red persimmon varieties. These fractions were quantified for their phenolic composition and assessed for their ability to promote the growth of beneficial human colonic Firmicutes species and for their in vitro anti-inflammatory potential. Gallic and protocatechuic acids, delphinidin, and cyanidin were the main phenolics identified. Faecalibacterium prausnitzii strains showed significantly higher growth rates in the presence of the Brilliant Red fraction, generating more than double butyrate as a proportion of the total short-chain fatty acids (39.5% vs. 17.8%) when compared to glucose. The fiber-rich fractions significantly decreased the inflammatory effect of interleukin-1β in Caco-2 cells, and the fermented fractions (both from Sharoni and Brilliant Red) significantly decreased the inflammatory effect of interleukin-6 and tumor necrosis factor-α in the RAW 264.7 cells. Therefore, fiber-rich fractions from persimmon by-products could be part of nutritional therapies as they reduce systemic inflammation, promote the growth of beneficial human gut bacteria, and increase the production of beneficial microbial metabolites such as butyrate.

The purple carrot cultivar 'Purple Sun' ( Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid ( 1 ), phenolic acid derivatives ( 2 and 6 ), hydroxycinnamic acid derivatives ( 9 , 10 , 12 - 14 , 16 , 17 , 19 , 22 , and 23 ), anthocyanins ( 3 - 5 , 7 , 8 , 11 , and 18 ), flavanonols ( 15 and 21 ), flavonols ( 20 and 24 ), oxylipins ( 25 , 26 , and 28 ), and the sesquiterpene 11-acetyloxytorilolone ( 27 ); compound 26 , corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (-) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus . The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, 'Purple Sun' is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations.

Anthocyanins are phenolic compounds occurring in fruits and vegetables. Evidence from pre-clinical studies indicates their role in glucose level regulation, gut microbiota improvement, and inflammation reduction under diabetic conditions. Therefore, incorporating these research advancements into clinical practice would significantly improve the prevention and management of type 2 diabetes. This narrative review provides a concise overview of 18 findings from recent clinical research published over the last 5 years that investigate the therapeutic effects of dietary anthocyanins on diabetes. Anthocyanin supplementation has been shown to have a regulatory effect on fasting blood glucose levels, glycated hemoglobin, and other diabetes-related indicators. Furthermore, increased anthocyanin dosages had more favorable implications for diabetes treatment. This review provides evidence that an anthocyanin-rich diet can improve diabetes outcomes, especially in at-risk groups. Future research should focus on optimal intervention duration, consider multiple clinical biomarkers, and analyze anthocyanin effects among well-controlled versus poorly controlled groups of patients with diabetes.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. Therefore, there is increasing interest in dietary interventions to reduce risk factors associated with these conditions. Cherries and berries are rich sources of bioactive compounds and have attracted attention for their potential cardiovascular benefits. This review summarises the current research on the effects of cherry and berry consumption on cardiovascular health, including in vivo studies and clinical trials. These red fruits are rich in phenolic compounds, such as anthocyanins and flavonoids, which have multiple bioactive properties. These properties include antioxidant, anti-inflammatory, and vasodilatory effects. Studies suggest that regular consumption of these fruits may reduce inflammation and oxidative stress, leading to lower blood pressure, improved lipid profiles, and enhanced endothelial function. However, interpreting findings and establishing optimal dosages is a challenge due to the variability in fruit composition, processing methods, and study design. Despite these limitations, the evidence highlights the potential of cherries and berries as components of preventive strategies against CVD. Further research is needed to maximise their health benefits and improve clinical practice.

Alzheimer's disease (AD) is the most common form of dementia and neurogenerative disease (NDD), and it is also one of the leading causes of death worldwide. The number of AD patients is over 55 million according to 2020 Alzheimer's Disease International (ADI), and the number is increasing drastically without any effective cure. In this review, we discuss and analyze the potential role of anthocyanins (ACNs) against AD while understanding the molecular mechanisms. ACNs have been reported as having neuroprotective effects by mitigating cognitive impairments, apoptotic markers, neuroinflammation, aberrant amyloidogenesis, and tauopathy. Taken together, ACNs could be an important therapeutic agent for combating or delaying the onset of AD.

Background: Circadian and homeostatic declines in cognitive performance are observed during the day, most commonly at 14:00. Additionally, postprandial reductions in cognitive ability have been widely demonstrated 1 h after lunch consumption, affecting domains of executive functioning (EF), episodic memory (EM), and attention. Existing evidence shows that anthocyanin-rich foods such as berries may improve or attenuate the decline in EF and EM in ageing adults. Further research is required to assess whether extracts such as wild blueberry extract (WBE) may be beneficial for cognitive function across an acute timeframe, including known periods of reduced functioning., Objectives: (1) Study 1: ROAB: To investigate the efficacy of WBE in maintaining EF and EM throughout the day alongside measures of cardiovascular outcomes in healthy older adults. A range of WBE doses were utilised to identify the optimal dose at which cognitive and cardiovascular effects occur. (2) Study 2: BEAT: To replicate alleviation of cognitive decline during a predicted post-lunch dip whilst also improving cardiovascular outcomes following acute WBE 222 mg supplementation., Methods: Both studies employed a randomised, double-blind, cross-over, placebo-controlled design to explore the effects of WBE intervention versus placebo on several outcomes, including EM, EF, blood pressure, and heart rate in a healthy older adult population (aged 68-75). In ROAB, 28 participants received a single dose of WBE 111 mg, 222 mg, 444 mg, or 888 mg or placebo over a 5-week period, each separated by a 1-week washout. Outcomes were measured at 0 h, 2 h, 4 h, and 6 h post intervention, with intervention occurring immediately after baseline (0 h). In BEAT, 45 participants received WBE 222 mg and placebo (1-week washout). Outcomes were measured at 0 h and 6 h (14:00) when a post-lunch dip was anticipated. This was further enhanced by consumption of lunch 1 h prior to cognitive testing. The WBE 222 mg intervention aligned with known peaks in plasma blueberry polyphenol metabolites at 2 h post dosing, which would coincide with a predicted drop in post-lunch performance., Results: ROAB: A significant dip in executive function was apparent at the 4 h timepoint for placebo only, indicating attenuation for WBE doses. Strikingly, WBE 222 mg produced acute reductions in both systolic and diastolic blood pressure compared with placebo. BEAT: EF reaction time was found to be significantly faster for WBE 222 compared to placebo at the predicted post-lunch dip (14:00), with no other notable benefits on a range of cognitive and cardiovascular outcomes., Conclusion: These two studies indicate that WBE may have cardiovascular benefits and attenuate the natural cognitive decline observed over the course of the day, particularly when a decline is associated with a circadian rhythm-driven postprandial dip. However, it is important to acknowledge that effects were subtle, and benefits were only observed on a small number of outcomes. Further research is required to explore the utility of WBE in populations already experiencing mild cognitive impairments.

Metabolic syndrome (MetS) is a significant health problem. The co-occurrence of obesity, carbohydrate metabolism disorders, hypertension and atherogenic dyslipidaemia is estimated to affect 20-30% of adults worldwide. Researchers are seeking solutions to prevent and treat the conditions related to MetS. Preventive medicine, which focuses on modifiable cardiovascular risk factors, including diet, plays a special role. A diet rich in fruits and vegetables has documented health benefits, mainly due to the polyphenolic compounds it contains. Anthocyanins represent a major group of polyphenols; they exhibit anti-atherosclerotic, antihypertensive, antithrombotic, anti-inflammatory and anticancer activities, as well as beneficial effects on endothelial function and oxidative stress. This review presents recent reports on the mechanisms involved in the protective effects of anthocyanins on the body, especially among people with MetS. It includes epidemiological data, in vivo and in vitro preclinical studies and clinical observational studies. Anthocyanins are effective, widely available compounds that can be used in both the prevention and treatment of MetS and its complications. Increased consumption of anthocyanin-rich foods may contribute to the maintenance of normal body weight and modulation of the lipid profile in adults. However, further investigation is needed to confirm the beneficial effects of anthocyanins on serum glucose levels, improvement in insulin sensitivity and reduction in systolic and diastolic blood pressure.

Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with multiple biological activities. This study aims to investigate the effects of C3G isolated from black rice on ALD and explore the potential mechanism. C57BL/6J mice (male) were fed with standard diet (CON) and Lieber-DeCarli liquid-fed (Eth) or supplemented with a 100 mg/kg/d C3G Diet (Eth-C3G), respectively. Our results showed that C3G could effectively ameliorate the pathological structure and liver function, and also inhibited the accumulation of liver lipids. C3G supplementation could partially alleviate the injury of intestinal barrier in the alcohol-induced mice. C3G supplementation could increase the abundance of Norank_f_Muribaculaceae , meanwhile, the abundances of Bacteroides , Blautia , Collinsella , Escherichia-Shigella , Enterococcus , Prevotella , [Ruminococcus]_gnavus_group , Methylobacterium-Methylorubrum , Romboutsia , Streptococcus , Bilophila , were decreased. Spearman's correlation analysis showed that 12 distinct genera were correlated with blood lipid levels. Non-targeted metabolic analyses of cecal contents showed that C3G supplementation could affect the composition of intestinal metabolites, particularly bile acids. In conclusion, C3G can attenuate alcohol-induced liver injury by modulating the gut microbiota and metabolites, suggesting its potential as a functional food ingredient against alcoholic liver disease.

Background: Epithelial-mesenchymal transition (EMT) plays an important role in the biological and biochemical processes of cells, and it is a critical process in the malignant transformation, and mobility of cancer. Additionally, EMT is one of the main mechanisms contributing to chemoresistance. Resistance to oxaliplatin (OXA) poses a momentous challenge in the chemotherapy of advanced colorectal cancer (CRC) patients, highlighting the need to reverse drug resistance and improve patient survival. In this study, we explored the response of cyanidin-3- O -glucoside (C3G), the most abundant anthocyanin in plants, on the mechanisms of drug resistance in cancer, with the purpose of overcoming acquired OXA resistance in CRC cell lines., Methods: We generated an acquired OXA-resistant cell line, named HCT-116-ROx, by gradually exposing parental HCT-116 cells to increasing concentrations of OXA. To characterize the resistance, we performed cytotoxicity assays and shape factor analyses. The apoptotic rate of both resistant and parental cells was determined using Hoechst 33342/Propidium Iodide (PI) fluorescence staining. Migration capacity was evaluated using a wound-healing assay. The mesenchymal phenotype was assessed through qRT-PCR and immunofluorescence staining, employing E-cadherin, N-cadherin, and Vimentin markers., Results: Resistance characterization announced decreased OXA sensitivity in resistant cells compared to parental cells. Moreover, the resistant cells exhibited a spindle cell morphology, indicative of the mesenchymal phenotype. Combined treatment of C3G and OXA resulted in an augmented apoptotic rate in the resistant cells. The migration capacity of resistant cells was higher than parental cells, while treatment with C3G decreased the migration rate of HCT-116-ROx cells. Analysis of EMT markers showed that HCT-116-ROx cells exhibited loss of the epithelial phenotype (E-cadherin) and gain of the mesenchymal phenotype (N-cadherin and Vimentin) compared to HCT-116 cells. However, treatment of resistant cells with C3G reversed the mesenchymal phenotype., Conclusion: The morphological observations of cells acquiring oxaliplatin resistance indicated the loss of the epithelial phenotype and the acquisition of the mesenchymal phenotype. These findings suggest that EMT may contribute to acquired OXA resistance in CRC. Furthermore, C3G decreased the mobility of resistant cells, and reversed the EMT process, indicating its potential to overcome acquired OXA resistance.

Late-life dementia is a growing public health concern lacking effective treatment. Neurodegenerative disorders such as Alzheimer's disease (AD) develop over a preclinical period of many years beginning in midlife. The prevalence of insulin resistance, a prominent risk factor for late-life dementia, also accelerates in middle-age. Consumption of berry fruits, including strawberries, has been shown to influence metabolism as well as cognitive performance suggesting potential to mitigate risk for dementia. In this controlled trial, we enrolled overweight middle-aged men and women with insulin resistance and subjective cognitive decline and performed a 12-week intervention with daily administration of whole-fruit strawberry powder. Diet records showed that participants in both groups maintained the prescribed abstinence from berry product consumption outside the study. We observed diminished memory interference ( p = 0.02; Cohen's f = 0.45) and a reduction of depressive symptoms ( p = 0.04; Cohen's f = 0.39) for the strawberry-treated participants; benefits consistent with improved executive ability. However, there was no effect of the intervention on metabolic measures, possibly a consequence of the sample size, length of the intervention, or comparatively low anthocyanin dose. Anti-inflammatory actions of anthocyanins were considered as a primary mechanistic factor. The findings support the notion that strawberry supplementation has a role in dementia risk reduction when introduced in midlife. However, further investigation with longer intervention periods, larger samples, and differing dosing regimens will be required to assess the benefits of strawberry intake with respect to cognition and metabolic function in the context of aging.

Anthocyanins (ACNs) have attracted considerable attention for their potential to modulate the immune system. Research has revealed their antioxidant and anti-inflammatory properties, which play a crucial role in immune regulation by influencing key immune cells, such as lymphocytes, macrophages, and dendritic cells. Moreover, ACNs contribute towards maintaining a balance between proinflammatory and anti-inflammatory cytokines, thus promoting immune health. Beyond their direct effects on immune cells, ACNs significantly impact gut health and the microbiota, essential factors in immune regulation. Emerging evidence suggests that they positively influence the composition of the gut microbiome, enhancing their immunomodulatory effects. Furthermore, these compounds synergize with other bioactive substances, such as vitamins and minerals, further enhancing their potential as immune-supporting dietary supplements. However, detailed clinical studies must fully validate these findings and determine safe dosages across varied populations. Incorporating these natural compounds into functional foods or supplements could revolutionize the management of immune-related conditions. Personalized nutrition and healthcare strategies may be developed to enhance overall well-being and immune resilience by fully understanding the mechanisms underlying the actions of their components. Recent advancements in delivery methods have focused on improving the bioavailability and effectiveness of ACNs, providing promising avenues for future applications.

Vaccinium uliginosum L. (commonly known as bog bilberry) and Vaccinium myrtillus L. (commonly known as bilberry) are species of the genus Vaccinium (family Ericaceae ). The red-purple-blue coloration of blueberries is attributed largely to the anthocyanins found in bilberries. Anthocyanins, known for their potent biological activity as antioxidants, have a significant involvement in the prophylaxis of cancer or other diseases, including those of metabolic origin. Bilberry is the most important economically wild berry in Northern Europe, and it is also extensively used in juice and food production. A review of the latest literature was performed to assess the composition and biological activity of V. uliginosum and V. myrtillus . Clinical studies confirm the benefits of V. uliginosum and V. myrtillus supplementation as part of a healthy diet. Because of their antioxidant, anti-inflammatory, anti-cancer, and apoptosis-reducing activity, both bog bilberries and bilberries can be used interchangeably as a dietary supplement with anti-free radical actions in the prevention of cancer diseases and cataracts, or as a component of sunscreen preparations.

Due to the rising demand for supplements targeting cognitive enhancement and dry eye together with the health benefits of anthocyanins, we have developed a functional soup containing an anthocyanin-rich functional ingredient, or "Anthaplex," and assessed the effects on cognitive function and eye dryness together with the possible mechanisms. A total of 69 male and female health volunteers were randomized and divided into placebo, D2, and D4 groups. All subjects consumed 120 mL of placebo or functional soup containing "Anthaplex" either at 2 or 4 g per serving per day within 5 min in the morning for eight weeks. The cognitive function, working memory, dry eye, AChE, MAO, MAO-A, MAO-B, and GABA-T activities, BDNF, HAC, HDAC, and DNMT activities, pH, and amount of lactic acid-producing bacteria, particularly Lactobacillus and Bifidobacterium spp. in feces, were determined before intervention and after eight weeks of consumption. Subjects who consumed the "Anthaplex" soup had improved cognitive function, working memory, eye dryness, histone acetylation, ACh E suppression, and BDNF with increased Bifidobacterium spp. but decreased pH in feces. These data suggest that "Anthaplex" improves cognitive function and eye dryness via the modulations of the histone acetylation process, gut microbiome, and cholinergic function.

Anthocyanins are flavonoid compounds that are abundantly present in fruits and vegetables. These compounds contribute to the color of these foods and offer various health benefits to consumers due to their biological properties. There are more than 1000 types of anthocyanins in nature, all derived from 27 anthocyanidin aglycones that have different glycosylations and acylations. Malvidin is one of the most well-known anthocyanidins. Several studies, including those conducted on cell lines, animals, and humans, have suggested that malvidin and its glycosides possess anti-carcinogenic, diabetes-control, cardiovascular-disease-prevention, and brain-function-improvement properties. These health benefits are primarily attributed to their antioxidant and anti-inflammatory effects, which are influenced by the molecular mechanisms related to the expression and modulation of critical genes. In this article, we review the available information on the biological activity of malvidin and its glycosides concerning their health-promoting effects.

The aim of the present study was to analyze the effects of cocoa flavanols and red berry anthocyanins on cardiovascular biomarkers, such as homocysteine, angiotensin-converting enzyme (ACE), nitric oxide (NO), flow-mediated vasodilation (FMD), blood pressure and lipid profile. Additionally, we aimed to ascertain their possible interactions with microbiota related metabolites, such as secondary bile acids (SBA), short-chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO). A randomized, parallel-group study, single-blind for the research team, was performed on 60 healthy volunteers between the ages of 45 and 85, who consumed 2.5 g/day of cocoa powder (9.59 mg/day of total flavanols), 5 g/day of a red berry mixture (13.9 mg/day of total anthocyanins) or 7.5 g/day of a combination of both for 12 weeks. The group that had consumed cocoa showed a significant reduction in TMAO ( p = 0.03) and uric acid ( p = 0.01) levels in serum, accompanied by an increase in FMD values ( p = 0.03) and total polyphenols. corrected by creatinine ( p = 0.03) after the intervention. These latter values negatively correlated with the TMAO concentration (R = -0.57, p = 0.02). Additionally, we observed an increase in carbohydrate fermentation in the groups that had consumed cocoa ( p = 0.04) and red berries ( p = 0.04) between the beginning and the end of the intervention. This increase in carbohydrate fermentation was correlated with lower levels of TC/HDL ratio ( p = 0.01), systolic ( p = 0.01) and diastolic blood pressure ( p = 0.01). In conclusion, our study showed a positive modulation of microbiota metabolism after a regular intake of cocoa flavanols and red berry anthocyanins that led to an improvement in cardiovascular function, especially in the group that consumed cocoa.

Obesity in the United States continues to worsen. Anthocyanin-rich fruits and vegetables provide a pragmatic dietary approach to slow its metabolic complications. Given American diet patterns, foods with high anthocyanin content could address dose-response challenges. The study objective was to determine the effect of 100% elderberry juice on measures of indirect calorimetry (IC) and insulin sensitivity/glucose tolerance in a placebo-controlled, randomized, crossover pilot study. Overweight and obese adults were randomized to a 5-week study which included 2 1-week periods of twice-daily elderberry juice (EBJ) or sugar-matched placebo consumption separated by a 3-week washout period. Following each 1-week test period, IC and insulin sensitivity/glucose tolerance was measured with a 3 h meal tolerance test (MTT). Treatment differences were tested with linear mixed modeling. A total of 22 prospective study volunteers (18 F/4 M) attended recruitment meetings, and 9 were analyzed for treatment differences. EBJ was well tolerated and compliance was 99.6%. A total of 6 IC measures (intervals) were created, which coincided with 10-20 min gaseous samplings in-between MTT blood samplings. Average CHO oxidation was significantly higher during the MTT after 1-week EBJ consumption (3.38 vs. 2.88 g per interval, EBJ vs. placebo, p = 0.0113). Conversely, average fat oxidation was significantly higher during the MTT after 1-week placebo consumption (1.17 vs. 1.47 g per interval, EBJ vs. placebo, p = 0.0189). This was in-line with a significantly lower average respiratory quotient after placebo treatment (0.87 vs. 0.84, EBJ vs. placebo, p = 0.0114). Energy expenditure was not different. There was no difference in serum glucose or insulin response between treatments. This pilot study of free-living volunteers describes significant change in IC but not insulin sensitivity with an EBJ intervention. Controlled feeding and increased sample size will help determine the utility of EBJ on these outcomes.

Berries and other anthocyanin-rich foods have demonstrated anti-obesity effects in rodents and humans. However, the bioactive components of these foods and their mechanisms of action are unclear. We conducted an intervention study with overweight and obese adults to isolate the effects of different berry components on bioenergetics. Subjects consumed whole mixed berries (high anthocyanin, high fiber), pressed berry juice (high anthocyanin, low fiber), berry-flavored gelatin (low anthocyanin, low fiber), or fiber-enriched gelatin (low anthocyanin, high fiber) for one week prior to a meal challenge with the same treatment food as the pre-feed period. Peripheral blood mononuclear cells were collected 2 h after the meal challenge, and cellular respiration was assessed via high-resolution respirometry. The high-anthocyanin, low-fiber treatment (berry juice) and the low-anthocyanin, high-fiber treatment (fiber-enriched gelatin) had opposite effects on cellular respiration. In the fasted state, berry juice resulted in the highest oxygen-consumption rate (OCR), while fiber-enriched gelatin resulted in the highest OCR in the fed state. Differences were observed in multiple respiration states (basal, state 3, state 4, uncoupled), with the greatest differences being between the pressed berry juice and the fiber-enriched gelatin. Different components of berries, specifically anthocyanins/flavonoids and fiber, appear to have differential effects on cellular respiration.

Cadmium (Cd) is a frequent environmental pollutant associated with biological toxicity that can harm female reproduction. Anthocyanins have been reported to reduce the toxicity of Cd. In the present study, the protective effects and underlying mechanisms of malvidin-3- O -glucoside (M3G) against the toxicity of Cd on female reproduction in KGN cells (human ovarian granulosa-like tumor cells) were investigated. After treating cells with 10 µmol/L cadmium chloride, the results showed that M3G lessened Cd-induced KGN cell cytotoxicity better than malvidin and malvidin-3,5- O -diglucoside. Additionally, M3G significantly decreased the Cd-induced generation of reactive oxygen species, inhibited the Cd-induced arrest of the G2/M phase of the cell cycle, and increased estradiol (E2) production. According to transcriptomic results, M3G reduced the abnormal expression of genes that responded to estrogen. Additionally, M3G promoted the endogenous synthesis and secretion of E2 by controlling the expression of CYP17A1 and HSD17B7. The current findings indicated that M3G is of great potential to prevent Cd-induced female reproductive impairment as a dietary supplement.

With the increase in human mean age, the prevalence of neurodegenerative diseases (NDs) also rises. This negatively affects mental and physiological health. In recent years, evidence has revealed that anthocyanins could regulate the functioning of the central nervous system (CNS) through the microbiome-gut-brain axis, which provides a new perspective for treating NDs. In this review, the protective effects and mechanisms of anthocyanins against NDs are summarized, especially the interaction between anthocyanins and the intestinal microbiota, and the microbial-intestinal-brain axis system is comprehensively discussed. Moreover, anthocyanins achieve the therapeutic purpose of NDs by regulating intestinal microflora and certain metabolites (protocateic acid, vanillic acid, etc.). In particular, the inhibitory effect of tryptophan metabolism on some neurotransmitters and the induction of blood-brain barrier permeability by butyrate production has a preventive effect on NDs. Overall, it is suggested that microbial-intestinal-brain axis may be a novel mechanism for the protective effect of anthocyanins against NDs.

A frequent chronic liver condition across the world is nonalcoholic fatty liver disease (NAFLD). Oxidative stress caused by lipid accumulation is generally considered to be the main cause of NAFLD. Anthocyanins can effectively inhibit the production of reactive oxygen species and improve oxidative stress. In this work, six major anthocyanins were separated from purple corncob by semi-preparative liquid chromatography. The effects of the 6 kinds of anthocyanins against NAFLD were investigated using a free fatty acid (FFA)-induced cell model. The results showed that peonidin 3-O-glucoside (P3G) can significantly reduce lipid accumulation in the NAFLD cell model. The treatment with P3G also inhibited oxidative stress via inhibiting the excessive production of reactive oxygen species and superoxide anion, increasing glutathione levels, and enhancing the activities of SOD, GPX, and CAT. Further studies unveiled that treatment with P3G not only alleviated inflammation but also improved the depletion of mitochondrial content and damage of the mitochondrial electron transfer chain developed concomitantly in the cell model. P3G upregulated transcription factor EB (TFEB)-mediated lysosomal function and activated the peroxisome proliferator-activated receptor alpha (PPARα)-mediated peroxisomal lipid oxidation by interacting with PPARα possibly. Overall, this study added to our understanding of the protective effects of purple corn anthocyanins against NAFLD and offered suggestions for developing functional foods containing these anthocyanins.

Black raspberries (BRB) are rich in anthocyanins with purported anti-inflammatory properties. However, it is not known whether dietary supplementation would ameliorate Western-diet enhanced gut inflammation and colon tumorigenesis. We employed a mouse model of colitis-associated colorectal cancer (CAC) to determine the effects of dietary supplementation with 5 to 10% ( w / w ) whole, freeze-dried BRB in male C57BL/6J mice fed either a standard healthy diet (AIN93G) or the total Western diet (TWD). In a pilot study, BRB suppressed colitis and colon tumorigenesis while also shifting the composition of the fecal microbiome in favor of taxa with purported health benefits, including Bifidobacterium pseudolongum . In a follow-up experiment using a 2 × 2 factorial design with AIN and TWD basal diets with and without 10% ( w / w ) BRB, supplementation with BRB reduced tumor multiplicity and increased colon length, irrespective of the basal diet, but it did not apparently affect colitis symptoms, colon inflammation or mucosal injury based on histopathological findings. However, BRB intake increased alpha diversity, altered beta diversity and changed the relative abundance of Erysipelotrichaceae, Bifidobacteriaceae, Streptococcaceae, Rikenellaceae, Ruminococcaceae and Akkermansiaceae, among others, of the fecal microbiome. Notably, changes in microbiome profiles were inconsistent with respect to the basal diet consumed. Overall, these studies provide equivocal evidence for in vivo anti-inflammatory effects of BRB on colitis and colon tumorigenesis; yet, BRB supplementation led to dynamic changes in the fecal microbiome composition over the course of disease development.

Black corn has been attracting attention to investigate its biological properties due to its anthocyanin composition, mainly cyanidin-3-glucoside. Our study evaluated the effects of black corn extract (BCE) on intestinal morphology, gene expression, and the cecal microbiome. The BCE intra-amniotic administration was evaluated by an animal model in Gallus gallus . The eggs ( n = 8 per group) were divided into: (1) no injection; (2) 18 MΩ H 2 O; (3) 5% black corn extract (BCE); and (4) 0.38% cyanidin-3-glucoside (C3G). A total of 1 mL of each component was injected intra-amniotic on day 17 of incubation. On day 21, the animals were euthanized after hatching, and the duodenum and cecum content were collected. The cecal microbiome changes were attributed to BCE administration, increasing the population of Bifidobacterium and Clostridium, and decreasing E. coli. The BCE did not change the gene expression of intestinal inflammation and functionality. The BCE administration maintained the villi height, Paneth cell number, and goblet cell diameter (in the villi and crypt), similar to the H 2 O injection but smaller than the C3G. Moreover, a positive correlation was observed between Bifidobacterium , Clostridium , E. coli , and villi GC diameter. The BCE promoted positive changes in the cecum microbiome and maintained intestinal morphology and functionality.

Açaí, lychee, mamey, passion fruit and jackfruit are some lesser-consumed tropical fruits due to their low commercial production. In 2018, approximately 6.8 million tons of these fruits were harvested, representing about 6.35% of the total world production of tropical fruits. The present work reviews the nutritional content, profile of bioactive compounds, antioxidant and anti-inflammatory capacity of these fruits and their by-products, and their ability to modulate oxidative stress due to the content of phenolic compounds, carotenoids and dietary fiber. Açaí pulp is an excellent source of anthocyanins (587 mg cyanidin-3-glucoside equivalents/100 g dry weight, dw), mamey pulp is rich in carotenoids (36.12 mg β-carotene/100 g fresh weight, fw), passion fruit peel is rich in dietary fiber (61.16 g/100 dw). At the same time, jackfruit contains unique compounds such as moracin C, artocarpesin, norartocarpetin and oxyresveratrol. These molecules play an important role in the regulation of inflammation via activation of mitogen-activated protein kinases (including p38, ERK and JNK) and nuclear factor κB pathways. The properties of the bioactive compounds found in these fruits make them a good source for use as food ingredients for nutritional purposes or alternative therapies. Research is needed to confirm their health benefits that can increase their marketability, which can benefit the primary producers, processing industries (particularly smaller ones) and the final consumer, while an integral use of their by-products will allow their incorporation into the circular bioeconomy.

Driven by the modern lifestyle, the consumers are interested in healthier and balanced diets, including both probiotics and natural antioxidants. The beneficial health effects of probiotics are mainly due to their capacity of modulating the human intestinal microbiota, although achieving at least a 6 log of viable cells at the targeted site is still challenging. Therefore, in this study, an attempt to improve the bioaccessibility of Lacticaseibacillus casei ( L. casei ) 431 ® through a co-microencapsulation by complex coacervation and freeze-drying, using an extract from Cornelian cherry and two biopolymeric matrices, whey protein isolates and casein (WPI-CN) and inulin (WPI-I), was studied. The powders showed a comparable anthocyanin content of around 32.00 mg cyanidin-3-rutinoside (C3R)/g dry matter (DM) and a microbial load of about 10 Log CFU/g DM. A high stability of the lactic acid bacteria was assessed throughout 90 days of storage, whereas the anthocyanins' degradation during storage followed a first order kinetic model, allowing the estimation of a half-time of 66.88 ± 1.67 days for WPI-CN and 83.60 ± 2.46 days for WPI-I. The in vitro digestion showed a high stability of anthocyanins in the simulated gastric juice, whereas the release in the simulated intestinal juice was favored in the variant with inulin (up to 38%). The use of casein permitted to obtain finer spherosomes, with smaller diameters, whereas a double encapsulation was obvious in both variants, thus explaining the high resistance in the gastric environment. The anti-proliferative effect against the human colon cancer cell line (HT-29) was also demonstrated. No cytotoxicity has been found for the concentrations between 1 and 25 μg/mL for the WPI-I variant, whereas a cell proliferation effect was observed at low concentrations of 1-5 μg/mL.

Oxidative stress and inflammation play a pivotal role in the development of cardiovascular diseases, an ever-growing worldwide problem. As a non-pharmacological approach, diet, especially a flavonoid-rich diet, showed promising results in the reduction of cardiovascular diseases and alleviation of their symptoms. In this study, in vitro systems based on human microvascular endothelial cells (hmvEC) and human umbilical cord endothelial cells (HUVEC) were established to determine the effect of Healthberry 865 ® (HB) and ten of its relating single anthocyanins on oxidative stress. Furthermore, five metabolites were used in order to examine the effect of anthocyanin's most common breakdown molecules. The results showed an effect of HB in both models after 24 h, as well as most of its single anthocyanins. Cyanidin-rutinoside, peonidin-galactoside, and petunidin-glucoside had a model-specific effect. For the metabolites, phloroglucinaldeyhde (PGA) showed an effect in both models, while vanillic acid (VA) only had an effect in HUVEC. When combined, a combination of several anthocyanins did not have a cumulative effect, except for combining glucosides in hmvEC. The combination of PGA and VA even revealed an inhibitive behavior. Overall, the study demonstrates the antioxidative effect of HB and several of its single anthocyanins and metabolites, which are partially model specific, and coincides with animal studies.

Cardiovascular disease (CVD) is a group of diseases affecting the heart and blood vessels and is the leading cause of morbidity and mortality worldwide. Increasingly more evidence has shown that the senescence of vascular endothelial cells is the key to endothelial dysfunction and cardiovascular diseases. Anthocyanin is a type of water-soluble polyphenol pigment and secondary metabolite of plant-based food widely existing in fruits and vegetables. The gut microbiome is involved in the metabolism of anthocyanins and mediates the biological activities of anthocyanins and their metabolites, while anthocyanins also regulate the growth of specific bacteria in the microbiota and promote the proliferation of healthy anaerobic flora. Accumulating studies have shown that anthocyanins have antioxidant, anti-inflammatory, and anti-aging effects. Many animal and in vitro experiments have also proven that anthocyanins have protective effects on cardiovascular-disease-related dysfunction. However, the molecular mechanism of anthocyanin in eliminating aging endothelial cells and preventing cardiovascular diseases is very complex and is not fully understood. In this systematic review, we summarize the metabolism and activities of anthocyanins, as well as their effects on scavenging senescent cells and cardioprotection.

Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5−100 μg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1β, and IL-18 inflammatory gene expressions and IL-6, IL-1β, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25−10 μg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.

The purple-flesh potato ( Solanum tuberosum L.) cultivar "Shadow Queen" (SQ) naturally contains anthocyanins. This randomized, double-blind, placebo-controlled study determines whether ingesting purple potatoes increases the number of mesenchymal stem cells (MSC) and improves stress response, a minor health complaint in healthy adults (registration number: UMIN000038876). A total of 15 healthy subjects (ages: 50-70 years) with minor health complaints were randomly assigned to one of two groups. For 8 weeks, the placebo group received placebo potatoes cv. "Haruka" and the test group received test potato cv. SQ containing 45 mg anthocyanin. The MSC count and several stress responses were analyzed at weeks 0 and 8 of the intake periods. The ingestion of a SQ potato did not affect the MSC count but markedly improved psychological stress response, irritability, and depression as minor health complaints compared with "Haruka". No adverse effects were noted. Hence, an 8-week intake of SQ could improve stress responses.

Rice is one of the most important food crops in many countries, with nutritional value and health benefits. In this study, the ethanolic and aqueous extracts of red jasmine rice from Chiang Mai, Thailand were examined for their anthocyanins and phenolic contents. The antioxidant and antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as well as anticancer activity, were investigated. The total anthocyanins content of 708.03 ± 11.56 mg Cy-3-glc equivalent/g extract, determined from the ethanolic extract, was higher than the aqueous extract. However, the aqueous extract showed the highest total phenolic compound of 81.91 ± 0.51 mg GAE/g extract. In addition, the ethanolic extract demonstrated higher antioxidant activity than aqueous extract using DPPH, ABTS, and FRAP assays by 28.91 ± 3.26 mg GAE/g extract, 189.45 ± 11.58 mg 24 TEAC/g extract, and 3292.46 ± 259.64 g FeSO 4 /g extract, respectively. In the antiviral assay, it was found that the ethanolic extract of red jasmine rice could inhibit HSV-1 more effectively than HSV-2 when treated before, during, and after the viral attachment on Vero cells, with 50% effective doses of 227.53 ± 2.41, 189.59 ± 7.76, and 192.62 ± 2.40 µg/mL, respectively. The extract also demonstrated the highest reduction of HSV-1 particles at 4 h after treatment and the inhibition of HSV-1 replication. The ethanolic extract exhibited a higher toxicity level than the aqueous extract, as well as the potential to induce DNA fragmentation by intrinsic and extrinsic apoptosis pathways on the Caco-2 cells. These findings suggest that red jasmine rice extract demonstrates nutritional value and biological activity on HSV, free radicals, and cancer cell inhibition.

Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one proanthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechanisms utilizing premalignant Barrett's esophagus (BE) and EAC derived cell lines. We employed reverse phase protein arrays (RPPA) and Western blots to examine cancer-associated pathways and specific signaling cascades modulated by C-PAC or AFG. Viability results show that C-PAC is more potent than AFG at inducing cell death in BE and EAC cell lines. Based on the RPPA results, C-PAC significantly modulated 37 and 69 proteins in JH-EsoAd1 (JHAD1) and OE19 EAC cells, respectively. AFG treatment significantly altered 49 proteins in both JHAD1 and OE19 cells. Bioinformatic analysis of RPPA results revealed many previously unidentified pathways as modulated by cranberry polyphenols including NOTCH signaling, immune response, and epithelial to mesenchymal transition. Collectively, these results provide new insight regarding mechanisms by which cranberry polyphenols exert cancer inhibitory effects targeting EAC, with implications for potential use of cranberry constituents as cancer preventive agents.

The aim of this review was to explore existing evidence from studies conducted on humans and summarize the mechanisms of action of dietary polyphenols on vascular health, blood pressure and hypertension. There is evidence that some polyphenol-rich foods, including berry fruits rich in anthocyanins, cocoa and green tea rich in flavan-3-ols, almonds and pistachios rich in hydroxycinnamic acids, and soy products rich in isoflavones, are able to improve blood pressure levels. A variety of mechanisms can elucidate the observed effects. Some limitations of the evidence, including variability of polyphenol content in plant-derived foods and human absorption, difficulty disentangling the effects of polyphenols from other dietary compounds, and discrepancy of doses between animal and human studies should be taken into account. While no single food counteracts hypertension, adopting a plant-based dietary pattern including a variety of polyphenol-rich foods is an advisable practice to improve blood pressure.

This study aimed to assess the efficacy of a blood orange Citrus sinensis standardized extract from “Moro” cultivar, on weight loss in overweight but otherwise healthy individuals. Anthocyanins and particularly cyanidin 3-glucoside, found in a large variety of fruits including Sicilian blood oranges, can help to counteract weight gain and to reduce body fat accumulation through the modulation of antioxidant, anti-inflammatory and metabolic pathways. In this randomized, double blind, placebo-controlled study, all participants (overweight adults aged 20−65 years old) were randomized to receive either Moro blood orange standardized extract or a placebo daily for 6-months. The primary outcome measure was change in body mass and body composition at the end of the study. After 6-months, body mass (4.2% vs. 2.2%, p = 0.015), body mass index (p = 0.019), hip (3.4 cm vs. 2.0 cm, p = 0.049) and waist (3.9 cm vs. 1.7 cm, p = 0.017) circumferences, fat mass (p = 0.012) and fat distribution (visceral and subcutaneous fat p = 0.018 and 0.006, respectively) were all significantly better in the extract supplemented group compared to the placebo (p < 0.05). In addition, all safety markers of liver toxicity were within the normal range throughout the study for both analyzed groups. Concluding, the present study demonstrates that Moro blood orange standardized extract may be a safe and effective option for helping with weight loss when used in conjunction with diet and exercise.

In recent decades, the elderly population has increased at higher rates than any other population group, resulting in an increase in age-related diseases such as neurodegenerative and cognitive impairment. To address this global health problem, it is necessary to search for new dietary strategies that can prevent the main neurocognitive problems associated with the ageing process. Therefore, the aim of the present study was to analyze the effect of cocoa flavanols and red berry anthocyanins on brain-derived neurotrophic factor (BDNF) and nerve growth factor receptor (NGF-R) and to stablish the possible improvement in cognitive performance by using a battery of neurocognitive tests that included the Verbal Learning Test Spain-Complutense, the Spatial Recall Test 10/36 BRB-N, the Wechsler Adult Intelligence Scale III and IV, the STROOP Task and the Tower of London Test. A randomized, double-blind, parallel-group study was performed in 60 healthy volunteers between 50 and 75 years old who consumed a cocoa powder, a red berries mixture or a combination of both for 12 weeks. After the intervention, we observed a reduction in the time needed to start ( p = 0.031) and finish ( p = 0.018) the neurocognitive test known as the Tower of London in all groups, but the decrease in time to finish the task was more pronounced in the intervention with the combination of cocoa-red berries group. We failed to show any significant difference in BDNF and NGF-R sera levels. However we found a negative correlation between BDNF and the number of movements required to finish the TOL in women ( p = 0.044). In conclusion, our study showed an improvement in executive function, without any change in neurotrofin levels, for all intervention arms.

Age-related macular degeneration (AMD) is one of the major causes of blindness in elderly populations. However, the dry form of AMD has lack of effective treatments. The fruits of Aronia melanocarpa are rich in anthocyanins. In this study, the protective effects of aronia fruit extract on rat retina were investigated using a NaIO 3 -induced dry AMD model. Full-field electroretinograms (ERGs) showed that b-wave amplitudes were significantly decreased and the retina structures were disordered in the model. The extract treatment alleviated the injuries. The b-wave amplitudes increased 61.5% in Scotopic 0.01ERG, 122.0% in Photopic 3.0ERG, and 106.8% in Photopic 3.0 flicker; the retina structure disorder was improved with the thickness of outer nuclear layer increasing by 44.1%; and the malonaldehyde level was significantly reduced in extract-treated rat retinas compared to the model. The proteomics analysis showed the expressions of five crystallin proteins, α-crystallin A chain, β-crystallin B2, β-crystallin A3, α-crystallin B chain, and γ-crystallin S, which protect retina ganglion cells, were increased by 7.38-, 7.74-, 15.30-, 4.86-, and 9.14-fold, respectively, in the extract treatment compared to the control, which was also confirmed by immunoblotting. The results suggest that aronia fruit extract, probably due to its anthocyanins, could protect the rat retina by alleviating oxidative damages and by upregulating the crystallin proteins to protect its nerve system.

(1) Background: The anthocyanin delphinidin exhibits anti-angiogenic properties both in in vitro and in vivo angiogenesis models. However, in vivo delphinidin is poorly absorbed, thus its modest bioavailability and stability reduce its anti-angiogenic effects. The present work takes advantage of small extracellular vesicle (sEV) properties to enhance both the stability and efficacy of delphinidin. When encapsulated in sEVs, delphinidin inhibits the different stages of angiogenesis on human aortic endothelial cells (HAoECs). (2) Methods: sEVs from immature dendritic cells were produced and loaded with delphinidin. A method based on UHPLC-HRMS was implemented to assess delphinidin metabolites within sEVs. Proliferation assay, nitric oxide (NO) production and Matrigel assay were evaluated in HAoECs. (3) Results: Delphinidine, 3-O-β-rutinoside and Peonidin-3-galactoside were found both in delphinidin and delphinidin-loaded sEVs. sEV-loaded delphinidin increased the potency of free delphinidin 2-fold for endothelial proliferation, 10-fold for endothelial NO production and 100-fold for capillary-like formation. Thus, sEV-loaded delphinidin exerts effects on the different steps of angiogenesis. (4) Conclusions: sEVs may be considered as a promising approach to deliver delphinidin to target angiogenesis-related diseases, including cancer and pathologies associated with excess vascularization.

Cornelian cherry ( Cornus mas L.) fruits possess potential cardiovascular, lipid-lowering and hypoglycemic bioactivities. The aim of this study is to evaluate the influence of resin-purified cornelian cherry extract rich in iridoids and anthocyanins on several transcription factors, intima/media ratio in aorta and serum parameters, which determine or are valuable indicators of the adverse changes observed in the course of atherosclerosis, cardiovascular disease, and metabolic syndrome. For this purpose, male New Zealand rabbits were fed a diet enriched in 1% cholesterol for 60 days. Additionally, one group received 10 mg/kg b.w. of cornelian cherry extract and the second group 50 mg/kg b.w. of cornelian cherry extract. PPAR-α and PPAR-γ expression in the aorta, LXR-α expression in the liver; cholesterol, triglycerides, adipokines, apolipoproteins, glucose and insulin levels in serum; the intima and media diameter in the thoracic and abdominal aorta were determined. Administration of cornelian cherry extract resulted in an enhancement in the expression of all tested transcription factors, a decrease in triglycerides, leptin and resistin, and an increase in adiponectin levels. In addition, a significant reduction in the I/M ratio was observed for both the thoracic and abdominal aorta. The results we have obtained confirm the potential contribution of cornelian cherry extract to mitigation of the risk of developing and the intensity of symptoms of obesity-related cardiovascular diseases and metabolic disorders such as atherosclerosis or metabolic syndrome.

Peptic ulcer episodes cause damage to the stomach and intestine, with inflammatory cell infiltration and oxidative stress as the main players. In this study, we investigated the potential of anthocyanidin malvidin for preventive and curative peptic ulcer treatment. The anthocyanidin effects were examined in gastric ulcer mouse models induced by ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (IR), acetic acid and duodenal ulcer induced by polypharmacy. Expression levels of oxidative and inflammatory genes were measured to investigate the mechanism of anthocyanin activity. At a dose of 5 mg·kg -1 , Malvidin prevented gastric ulcer induction by ethanol, NSAID and repaired the tissue after 6 days of IR. Moreover, the anthocyanidin accelerated the healing of acetic acid-induced ulcer, increased the gene expression of EGF and COX-1, and downregulated MMP-9. Anthocyanin treatment mitigated the effect of polypharmacy on inflammation and oxidative stress observed in the intestine. Additionally, the compound downregulated cytokine expression and TLR4 and upregulated HMOX-1 and IL-10, exhibiting protective activity in the mouse gut. Malvidin thus prevented gastric and duodenal ulcers due to prominent anti-inflammatory and antioxidative effects on the gastrointestinal tract that were related to gene expression modulation and an increase in endogenous defense mechanisms.

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): -0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: -0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.

Oxidative stress and dysregulated adipocytokine secretion accompanying hypertrophied adipose tissue induce chronic inflammation, which leads to vascular endothelial dysfunction. The present study investigated the ability of anthocyanin (ACN) and non-anthocyanin polyphenol (PP) fractions from lingonberry fruit to mitigate adipose tissue hypertrophy and endothelial dysfunction using 3T3-L1 adipocytes and human umbilical vein endothelial cells (HUVECs). This study showed that the PP fraction decreased intracellular ROS generation in hypertrophied adipocytes by enhancing antioxidant enzyme expression ( SOD2 ) and inhibiting oxidant enzyme expression ( NOX4 , iNOS ). Moreover, PP and ACN fractions reduced triglyceride content in adipocytes accompanied by downregulation of the expression of lipogenic genes such as aP2 , FAS , and DAGT1 . Treatment with both fractions modulated the mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression and secretion of leptin and adiponectin were, respectively, down- and upregulated. Furthermore, PP and ACN fractions alleviated the inflammatory response in TNF-α-induced HUVECs by inhibiting the expression of pro-inflammatory genes ( IL-6 , IL-1β ) and adhesion molecules ( VCAM-1 , ICAM-1 , SELE ). The obtained results suggest that consuming polyphenol-rich lingonberry fruit may help prevent and treat obesity and endothelial dysfunction due to their antioxidant and anti-inflammatory actions.

The pulp of the purple mangosteen, Garcinia mangostana , is a popular tropical fruit but the rind containing xanthones such as α-mangostin together with procyanidins and anthocyanidins is usually discarded as waste. However, this rind has been used in South-East Asia for diarrhoea, dysentery, skin infections and wounds. As xanthones have reported anti-inflammatory and antioxidant responses, this study has determined the bioactive compounds and evaluated the effects of G. mangostana rind on physiological, metabolic, liver and cardiovascular parameters in rats with diet-induced metabolic syndrome. Rats fed a diet with increased simple sugars and saturated fats developed obesity, hypertension, increased left ventricular stiffness, dyslipidaemia and fatty liver. Administration of G. mangostana rind as 5% of the food to rats with diet-induced metabolic syndrome gave a dose of 168 mg/kg/day α-mangostin, 355 mg/kg/day procyanidins, 3.9 mg/kg/day anthocyanins and 11.8 mg/kg/day hydroxycitric acid for 8 weeks which reduced body weight and attenuated physiological and metabolic changes in rats including decreased abdominal fat deposition, decreased abdominal circumference and whole-body fat mass, improved liver structure and function and improved cardiovascular parameters such as systolic blood pressure, left ventricular stiffness and endothelial function. These responses were associated with decreased infiltration of inflammatory cells, decreased deposition of collagen in both heart and liver and decreased mean adipocyte size in retroperitoneal adipose tissues. We conclude that, in rats with diet-induced metabolic syndrome, chronic intake of G. mangostana rind decreased infiltration of inflammatory cells which decreased physiological, metabolic, liver and cardiovascular symptoms., Competing Interests: The authors declare no conflict of interest.

Accumulating epidemiological evidence suggests that anthocyanin intake is associated with reduced risks of cardiometabolic disorders, highlighting the importance of incorporating the phytochemical in our diets. Numerous food-based intervention studies have examined, in controlled meal settings, the role of anthocyanin on cardiometabolic health; but their effects have not been systematically summarized. This study aims to systematically review and summarize the effects of anthocyanin consumption with composite meals on cardiometabolic health from randomized controlled feeding trials. A systematic literature search for relevant human nutritional intervention studies was performed using PubMed, Embase, Cochrane Library, CINAHL Plus with Full Text, and Scopus databases. The Cochrane Risk of Bias tool was used to assess the study quality. Eighteen articles involving 371 participants were included in this review. Consistent improvements from anthocyanin intake were found in glycemic, gastric inhibitory peptide (GIP), interleukin-6 (IL-6), and oxygen radical absorbance capacity (ORAC) responses. Anthocyanin intake did not significantly affect other markers of energy metabolism, vascular functions, oxidative stress and antioxidant status, as well as inflammatory responses. Inconsistencies in successful outcomes between epidemiological studies and included interventions were largely attributed to matrix effects, which may impede the bioaccessibility of anthocyanins and consequently, limiting its health benefits when co-delivered with some foods.

Cheongchunchal (CE) is a developed crop more highly enriched in cyanidin-3-O-glucoside chloride (anthocyanin) than conventional waxy corn. Anthocyanin has been proven to have anti-oxidant, anti-inflammatory, anti-obesity, and anti-cancer effects. In this study, using high-performance liquid chromatography (HPLC), Cheongchunchal was confirmed to contain 8.99 mg/g anthocyanin. The inhibitory effect of an ethanol extract of Cheongchunchal (CE) on adipocyte differentiation was demonstrated using Oil Red O staining and a triglyceride assay. By conducting Western blotting, we also confirmed the regulatory effect of CE on adipocyte differentiation factors by assessing changes in the levels of factors that play a significant role in the differentiation of 3T3-L1 preadipocytes. A C57BL/6N mouse model of obesity was induced with a high-fat diet, and CE (400, 600, and 800 mg/kg/day) or Garcinia (245 mg/kg/day) was orally administered to verify the anti-obesity effect of CE. As a result of CE administration, the food efficiency ratio (FER), weight gain, and weight of tissues decreased. Additionally, blood biochemical changes were observed. Furthermore, the inhibitory effect of CE on adipocytes was confirmed through morphological observation and the expression of adipocyte differentiation-related factors in the liver and fat tissues. Therefore, in this study, we verified the anti-obesity effects of anthocyanin-rich CE both in vitro and in vivo.

Diabetes mellitus (DM)-related morbidity and mortality are steadily rising worldwide, affecting about half a billion people worldwide. A significant proportion of diabetic cases are in the elderly, which is concerning given the increasing aging population. Proper nutrition is an important component in the effective management of diabetes in the elderly. A plethora of active substances of plant origin exhibit potency to target the pathogenesis of diabetes mellitus. The nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. In this study, the effect of Hungarian sour cherry, which is rich in anthocyanins, on hyperglycemia-induced endothelial dysfunction was tested using human umbilical cord vein endothelial cells (HUVECs). HUVECs were maintained under both normoglycemic (5 mM) and hyperglycemic (30 mM) conditions with or without two concentrations (1.50 ng/µL) of anthocyanin-rich sour cherry extract. Hyperglycemia-induced oxidative stress and inflammatory response and damaged vasorelaxation processes were investigated by evaluating the level of reactive oxygen species (ROS) and gene expression of four proinflammatory cytokines, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1α (IL-1α), as well as the gene expression of nitric oxide synthase (NOS) endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1). It was found that hyperglycemia-induced oxidative stress was significantly suppressed by anthocyanin-rich sour cherry extract in a concentration-dependent manner. The gene expression of the tested proinflammatory cytokines increased under hyperglycemic conditions but was significantly reduced by both 1 and 50 ng/µL anthocyanin-rich sour cherry extract. Further, although increased ET-1 and ECE-1 expression due to hyperglycemia was reduced by anthocyanin-rich sour cherry extract, NOS expression was increased by the extract. Collectively, these data suggest that anthocyanin-rich sour cherry extract could alleviate hyperglycemia-induced endothelial dysfunction due to its antioxidant, anti-inflammatory, and vasorelaxant effects.

Chronic low-grade inflammation is a primary characteristic of obesity and can lead to other metabolic complications including insulin resistance and type 2 diabetes (T2D). Several anti-inflammatory dietary bioactives decrease inflammation that accompanies metabolic diseases. We are specifically interested in delta-tocotrienol, (DT3) an isomer of vitamin E, and tart cherry anthocyanins (TCA), both of which possess individual anti-inflammatory properties. We have previously demonstrated that DT3 and TCA, individually, reduced systemic and adipose tissue inflammation in rodent models of obesity. However, whether these compounds have combinatorial effects has not been determined yet. Hence, we hypothesize that a combined treatment of DT3 and TCA will have great effects in reducing inflammation in adipocytes, and that these effects are mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), a major inflammatory transcription factor. We used 3T3-L1 adipocytes and treated them with 1-5 µM doses of DT3 along with tart cherry containing 18-36 µg anthocyanin/mL, to assess effects on inflammation. Neither DT3 nor TCA, nor their combinations had toxic effects on adipocytes. Furthermore, pro-inflammatory markers interleukin-6 (IL-6) and p-65 (subunit of NFkB) were reduced at the protein level in media collected from adipocytes with both individual and combined treatments. Additionally, other downstream targets of NFkB including macrophage inflammatory protein 2 ( Mip2 ), and Cyclooxygenase-2 ( Cox2 ) were also significantly downregulated ( p ≤ 0.05) when treated with individual and combined doses of DT3 and TCA with no additional combinatorial effects. In summary, DT3 and TCA individually, are beneficial in reducing inflammation with no additional combinatorial effects.

Scientists are focusing on bioactive ingredients to counteract obesity. We evaluated whether a mix containing grape seed proanthocyanidin extract (GSPE), anthocyanins, conjugated linoleic acid (CLA), and chicken feet hydrolysate (CFH) could reduce body fat mass and also determined which mechanisms in the white adipose tissue (WAT) and the brown adipose tissue (BAT) were affected by the treatment. The mix or vehicle (VH) were administered for three weeks to obese rats fed a cafeteria (CAF) diet. Biometric measures, indirect calorimetry, and gene expression in WAT and BAT were analyzed as was the histology of the inguinal WAT (IWAT). The individual compounds were also tested in the 3T3-L1 cell line. The mix treatment resulted in a significant 15% reduction in fat (25.01 ± 0.91 g) compared to VH treatment (21.19 ± 1.59 g), and the calorimetry results indicated a significant increase in energy expenditure and fat oxidation. We observed a significant downregulation of Fasn mRNA and an upregulation of Atgl and Hsl mRNA in adipose depots in the group treated with the mix. The IWAT showed a tendency of reduction in the number of adipocytes, although no differences in the total adipocyte area were found. GSPE and anthocyanins modulated the lipid content and downregulated the gene and protein levels of Fasn compared to the untreated group in 3T3-L1 cells. In conclusion, this mix is a promising treatment against obesity, reducing the WAT of obese rats fed a CAF diet, increasing energy expenditure and fat oxidation, and modifying the expression of genes involved in lipid metabolism of the adipose tissue.

Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome closely linked to dyslipidemia and gut microbiome dysbiosis. Bilberry anthocyanins (BA) have been reported to have preventive effects against metabolic syndrome. This study aimed to investigate the protective effects and mechanisms of BA in a Western diet (WD)-induced mouse model. The results revealed that supplementation with BA attenuated the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-c), fat content in liver, 2-thiobarbituric acid reactive substances (TBARS) and α-smooth muscle actin (α-SMA) caused by WD. Furthermore, gut microbiota characterized by 16S rRNA sequencing revealed that BA reduced remarkably the ratio of Firmicutes/Bacteroidetes (F/B) and modified gut microbiome. In particular, BA increased the relative abundance of g&#95; Akkermansia and g&#95; Parabacteroides . Taken together, our data demonstrated that BA might ameliorate WD-induced NAFLD by attenuating dyslipidemia and gut microbiome dysbiosis.

Insulin resistance (IR) is apparent when tissues responsible for clearing glucose from the blood, such as adipose and muscle, do not respond properly to appropriate signals. IR is estimated based on fasting blood glucose and insulin, but some measures also incorporate an oral glucose challenge. Certain (poly)phenols, as supplements or in foods, can improve insulin resistance by several mechanisms including lowering postprandial glucose, modulating glucose transport, affecting insulin signalling pathways, and by protecting against damage to insulin-secreting pancreatic β-cells. As shown by intervention studies on volunteers, the most promising candidates for improving insulin resistance are (-)-epicatechin, (-)-epicatechin-containing foods and anthocyanins. It is possible that quercetin and phenolic acids may also be active, but data from intervention studies are mixed. Longer term and especially dose-response studies on mildly insulin resistant participants are required to establish the extent to which (poly)phenols and (poly)phenol-rich foods may improve insulin resistance in compromised groups., Competing Interests: G.W. is an occasional consultant for Nutrilite, USA. K.S. declares no conflict of interest.

Coloured (black, purple, blue, red, etc.) cereal grains, rich in anthocyanins, have recently gained a lot of attention in the food industry. Anthocyanins are water-soluble flavonoids, and are responsible for red, violet, and blue colours in fruits, vegetables, and grains. Anthocyanins have demonstrated antioxidant potential in both in vitro and in vivo studies, and the consumption of foods high in anthocyanins has been linked to lower risks of chronic diseases. As such, whole grain functional foods made with coloured grains are promising new products. This paper will review the characteristics of cereal anthocyanins, and assess their prevalence in various commercially relevant crops including wheat, barley, maize, and rice. A brief overview of the antioxidant potential, and current research on the health effects of cereal-based anthocyanins will be provided. Finally, processing of coloured cereals in whole grain products will be briefly discussed. A full understanding of the fate of anthocyanins in whole grain products, and more research targeted towards health outcomes of anthocyanin supplementation to/inclusion in cereal food products are the next logical steps in this research field.

Blueberry (BB) consumption is linked to improved health. The bioconversion of the polyphenolic content of BB by fermentative bacteria in the large intestine may be a necessary step for the health benefits attributed to BB consumption. The identification of specific gut microbiota taxa that respond to BB consumption and that mediate the bioconversion of consumed polyphenolic compounds into bioactive forms is required to improve our understanding of how polyphenols impact human health. We tested the ability of polyphenol-rich fractions purified from whole BB-namely, anthocyanins/flavonol glycosides (ANTH/FLAV), proanthocyanidins (PACs), the sugar/acid fraction (S/A), and total polyphenols (TPP)-to modulate the fecal microbiota composition of healthy adults in an in vitro colon system. In a parallel pilot study, we tested the effect of consuming 38 g of freeze-dried BB powder per day for 6 weeks on the fecal microbiota of 17 women in two age groups (i.e., young and older). The BB ingredients had a distinct effect on the fecal microbiota composition in the artificial colon model. The ANTH/FLAV and PAC fractions were more effective in promoting microbiome alpha diversity compared to S/A and TPP, and these effects were attributed to differentially responsive taxa. Dietary enrichment with BB resulted in a moderate increase in the diversity of the microbiota of the older subjects but not in younger subjects, and certain health-relevant taxa were significantly associated with BB consumption. Alterations in the abundance of some gut bacteria correlated not only with BB consumption but also with increased antioxidant activity in blood. Collectively, these pilot data support the notion that BB consumption is associated with gut microbiota changes and health benefits.