Association between Flavonoid Intake and Cognitive Executive Function among African American and White Adults in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) Study.

Healthy dietary patterns rich in flavonoids may benefit cognitive performance over time. Among socioeconomically disadvantaged groups, the association between flavonoid intake and measures of cognition is unclear. This study sought to identify associations between flavonoid intake and cognitive performance among Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study participants (n = 1947) across three study visits. Flavonoid intakes were assessed via two 24-h dietary recalls. Cognitive performance was assessed via the Trail Making Test (TMT)-A and TMT-B, which provide measures of attention and executive function, respectively. Mixed effects linear regression was used to model TMT scores over three study visits against visit 1 (v1) flavonoid intake, time (years from v1), and the interaction between v1 flavonoid intake and time, capturing both the cross-sectional association between flavonoid intake and time at v1 as well as the longitudinal association between v1 flavonoid intake and the change in TMT scores over time. Prior to adjustment, inverse cross-sectional associations at v1 were observed between (1) anthocyanidin intake and TMT-A scores for the overall sample and (2) total flavonoid, anthocyanidin, flavan-3-ol, flavone, and flavonol intake and TMT-B scores for the overall sample and among White adults. Only the association between anthocyanidin intake and TMT-B at v1 among White adults persisted after adjustment (for demographic characteristics such as age). One possible explanation for the few significant associations is universally low flavonoid intakes resulting from the consumption of an unhealthy dietary pattern.

Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of metabolic syndrome among females: Results from NHANES 2007-2010 and 2017-2018.

OBJECTIVE: Known for anti-inflammatory and antioxidant properties, flavonoid has phytoestrogenic effects, but it is unclear whether its role in hyperuricemia and metabolic syndrome (MetS) differs by gender. Moreover, given the strong association between hyperuricemia and MetS, we aimed to explore whether flavonoid is a protective factor for hyperuricemia, independently of MetS, in different genders. METHODS: Data for 2007-2010 and 2017-2018 were obtained from the National Health and Nutrition Examination Survey (NHANES) and the Food and Nutrient Database for Dietary Studies (FNDDS). To assess the association among flavonoid, hyperuricemia, and MetS, multivariate logistic regression and subgroup analyses were conducted. Besides, to investigate whether the association between flavonoid and hyperuricemia was independent of MetS, multivariate logistic regression models were further conducted to explore the association between flavonoid and MetS among females with hyperuricemia and to investigate the association between flavonoid and hyperuricemia among females after excluding MetS. RESULT: Among 5356 females, anthocyanin intake was inversely associated with the prevalence of hyperuricemia (Q4 vs. Q1: OR 0.49, 95% CI 0.31 to 0.76), and MetS (Q4 vs. Q1: OR 0.68, 95% CI 0.50 to 0.93). Furthermore, subgroup analyses showed the beneficial association between anthocyanin and hyperuricemia among females aged 40 to 59 years and menopausal. However, among 5104 males, no significant association was observed after adjustment for covariates (Q4 vs. Q1: OR 0.81, 95% CI 0.56 to 1.18). While in 372 females with hyperuricemia, no significant association was found between MetS and anthocyanin (Q4 vs. Q1: OR 0.88, 95% CI 0.31 to 2.49). Meanwhile, among 3335 females after excluding MetS, there was still a significant association between anthocyanin and a lower prevalence of hyperuricemia (Q4 vs. Q1: OR 0.38, 95% CI 0.17 to 0.85). CONCLUSION: Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of MetS among females. Foods rich in anthocyanin should be emphasized for females, especially those aged 40 to 59 years and menopausal, which may be of potential significance in the prevention of hyperuricemia.

Association between dietary flavonoid intake and hypertension among U.S. adults.

Background: Hypertension is one of the major risk factors for cardiovascular disease. Dietary flavonoids have been reported to reduce inflammation, protect against oxidative stress, protect the vascular endothelium, and improve vascular health. However, the relationship between dietary flavonoid intake and the prevalence of hypertension remains controversial. Methods: This study included 8010 adults from the 2007-2010 and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). The relationship between dietary flavonoid intake and the prevalence of hypertension was explored by weighted logistic regression and weighted restricted cubic spline. Results: We found an inverse relationship between total anthocyanin intake and the prevalence of hypertension in the fourth quartile compared with the first quartile [0.81(0.66,0.99), p = 0.04]. Moreover, the prevalence of hypertension tended to decrease with increasing total anthocyanin intake in participants over 60 years of age. In addition, we found a U-shaped relationship between the prevalence of hypertension and total flavan-3-ol intake. Total flavan-3-ol intake was inversely associated with hypertension prevalence in the third quartile compared with the first quartile [0.79 (0.63,0.99), p = 0.04]. Moreover, there was a significant negative association between the prevalence of hypertension and total flavan-3-ol intake when total flavan-3-ol intake was below 48.26 mg/day. Conclusion: Our study found a negative association between the prevalence of hypertension and moderate total anthocyanins intake and total flavan-3-ols intake. Our study provides evidence from a population-based study for a negative association between dietary flavonoid intake and the prevalence of hypertension.

Carboxymethyl Chitosan-Coated Cyanidin-3-O-Glucoside-Beared Nanonutriosomes Suppress Palmitic Acid-Induced Hepatocytes Injury.

Cyanidin-3-O-glucoside (C3G) is classified as an anthocyanin (ACN) and is recognized for its remarkable antioxidant properties. Yet, the inadequate physicochemical stability of C3G restricts its potential for various biological applications. Thus, in this study, carboxymethyl chitosan (CMC)-coated nanonutriosomes (NS) were synthesized as a novel carrier for encapsulating C3G (CMC-C3G-NS) to improve C3G stability. CMC-C3G-NS exhibited a diameter of less than 200 nm along with an encouraging encapsulation efficiency exceeding 90%. Notably, the formulated CMC-C3G-NS possessed better stability under various pH, ionic, and oxygen conditions, improved controlled release properties, and higher hepatocellular uptake than uncoated particles (C3G-NS), indicating a longer retention time of C3G in a physiological environment. Of utmost significance, CMC-C3G-NS demonstrated superior alleviating effects against palmitic acid (PA)-induced oxidative hepatic damage compared to C3G-NS. Our study provided promising nanocarriers with the potential to deliver hydrophilic ACNs and controlled release properties for PA-induced hepatotoxicity alleviation.

[Bioactive compounds anthocyanins as a factor in the nutritional recovery of the body's adaptive potential after intense physical activity in the experiment: assessment of immunological and hematological indicators of adaptation].

Restoring the adaptive potential of an athlete is of paramount importance not only for the implementation of his training and competitive activities, but also for maintaining health. One of the leading place in complex recovery programs in sports is given to full-fledged optimal nutrition, which provides for meeting the body's requirements not only in energy, macro- and micronutrients, but also in minor bioactive compounds. The use of anthocyanin-containing products is a promising strategy for the normalization of metabolic and immune disorders that develop as a result of intense physical and neuro-emotional stress not only in athletes, but also in other groups of people exposed to these factors, including military personnel undergoing training in conditions close to combat. This determines the relevance of this study. The aim of the research was to study the effect of an anthocyanin-enriched diet on hematological profile and cellular immunity in rats after intense physical activity. Material and methods. The experiment was carried out for 4 weeks on 4 groups of male Wistar rats with an initial body weight of ~300 g. The motor activity of the animals of the 1st (control) and 2nd groups was limited by the standard keeping animals in the vivarium, while physically active rats of the 3rd and 4th groups received additional physical activity - training on a treadmill. Before the end of the experiment, the animals of 3rd and 4th groups were given debilitating physical activity on a treadmill (until the rats refused to continue the exercise). Rats of all 4 groups received a standard semi-synthetic diet, water ad libitum. Animals in 2nd and 4th groups were additionally fed blueberry and blackcurrant extract (30% anthocyanins) as part of the diet at a daily dose of 15 mg anthocyanins/kg body weight. Hematological parameters were determined on a Coulter ACT TM 5 diff OV hematological analyzer. Expression of CD45R, CD3, CD4, CD8a, CD161 receptors on rat peripheral blood lymphocytes was determined by direct immunofluorescent staining of whole blood cells using a panel of monoclonal antibodies conjugated with fluorescent dyes: APC, FITC, PE. The measurements were carried out on an FC-500 flow cytometer. Results. Intense physical activity in rats of the 3rd group did not lead to a significant change in erythrocyte parameters compared with the control group. Enrichment of the diet with blueberry and black currant extract (the 2nd and the 4th groups) provided a significant (p<0.05) increase in blood content of hemoglobin (Hb) (150.7±0.9 and 154.4±2.0 vs 145.4±0.9 g/l in control), hematocrit (44.95±0.21 and 46.18±0.64 vs 43.78±0.32%) and the average content of Hb in erythrocytes (18.00±0.20 and 18.03±0.24 vs 17.35±0.24 pg). The absolute content of leukocytes and other cellular elements of the leukocyte formula, as well as leukocyte indices in rats of the experimental groups didn't significantly differ from those of the control rats, which confirms the absence of an inflammatory process. Intense physical activity and anthocyanin enrichment of the diet didn't have a significant effect on rat platelet parameters. Enrichment of the diet of rats of the 4th group with blueberry and black currant extract led to the activation of cellular immunity, as evidenced by a significant (p<0.01) increase in the percentage (from the total content of T-lymphocytes) of T-helpers (70.13 ±1.34 vs 63.75±0.99%) and a decrease in the relative content of cytotoxic T-lymphocytes (28.65±1.38 vs 34.71±0.95%) in comparison with those in rats of the 3rd group and at the level of the trend (р<0.1) - from the 1st group indexes (66.87±1.20 and 31.87±1.26%, accordingly). Intense physical activity led to a decrease in immunoregulatory index in rats of the 3rd group (1.86±0.07) compared with the control (2.13±0.12) (p<0.1), and in animals of the 4th group this indicator was significantly higher (2.50±0.14, p<0.05). In animals of the 3rd group a statistically significant (p<0.05) decrease in the relative content of NK cells in peripheral blood was found compared to the control. Enrichment of the diet of physically active rats with blueberry and black currant extract led to a significant (p<0.05) increase in the percentage of NK cells compared to this indicator in rats of the 3rd group (4.87±0.75 vs 2.08±0.18%) and had no significant difference with the indicator in rats of the control group (4.32±0.98%). Conclusion. The enrichment of the rats' diet with blueberry and blackcurrant extract containing a daily dose of 15 mg of anthocyanins per kg of body weight provides an increase in blood Hb content, hematocrit and the average content Hb in erythrocytes. It has been established that intense physical activity induces the cellular immunity suppression. The activating effect of anthocyanins on adaptive cellular immunity and NK cells, which are lymphocytes of innate immunity, was revealed. The data obtained indicate the effectiveness of the use of bioactive compounds (anthocyanins) to increase the adaptive potential of the organism.

Cyanidin attenuates the apoptosis of rat nucleus pulposus cells and the degeneration of intervertebral disc via the JAK2/STAT3 signal pathway in vitro and in vivo.

CONTEXT: Cyanidin has been shown to have therapeutic potential in osteoarthritis. However, it is unclear whether cyanidin prevents the progression of intervertebral disc degeneration (IVDD). OBJECTIVE: This study evaluates the effects of cyanidin on IVDD in vitro and in vivo. MATERIALS AND METHODS: Nucleus pulposus cells (NPCs) isolated from lumbar IVD of 4-week-old male Sprague-Dawley (SD) rats were exposed to 20 ng/mL IL-1ß, and then treated with different doses (0-120 µM) of cyanidin for 24 h. SD rats were classified into three groups (n = 8) and treated as follows: control (normal saline), IVDD (vehicle), IVDD + cyanidin (50 mg/kg). Cyanidin was administered intraperitoneally for 8 weeks. RESULTS: The IC50 of cyanidin for NPCs was 94.78 µM, and cyanidin had no toxicity at concentrations up to 500 mg/kg in SD rats. Cyanidin inhibited the apoptosis of NPCs induced by IL-1ß (12.73 ± 0.61% vs. 18.54 ± 0.60%), promoted collagen II (0.82-fold) and aggrecan (0.81-fold) expression, while reducing MMP-13 (1.02-fold) and ADAMTS-5 (1.40-fold) expression. Cyanidin increased the formation of autophagosomes in IL-1ß-induced NPCs, and promoted LC3II/LC3I (0.83-fold) and beclin-1 (0.85-fold) expression, which could be reversed by chloroquine. Cyanidin inhibited the phosphorylation of JAK2 (0.47-fold) and STAT3 (0.53-fold) in IL-1ß-induced NPCs. The effects of cyanidin could be enhanced by AG490. Furthermore, cyanidin mitigated disc degeneration in IVDD rats in vivo. DISCUSSION AND CONCLUSIONS: Cyanidin improved the function of NPCs in IVDD by regulating the JAK2/STAT3 pathway, which may provide a novel alternative strategy for IVDD. The mechanism of cyanidin improving IVDD still needs further work for in-depth investigation.

Blueberry anthocyanin intake attenuates the postprandial cardiometabolic effect of an energy-dense food challenge: Results from a double blind, randomized controlled trial in metabolic syndrome participants.

BACKGROUND & AIMS: Whilst the cardioprotective effects of blueberry intake have been shown in prospective studies and short-term randomized controlled trials (RCTs), it is unknown whether anthocyanin-rich blueberries can attenuate the postprandial, cardiometabolic dysfunction which follows energy-dense food intakes; especially in at-risk populations. We therefore examined whether adding blueberries to a high-fat/high-sugar meal affected the postprandial cardiometabolic response over 24 h. METHODS: A parallel, double-blind RCT (n = 45; age 63.4 ± 7.4 years; 64% male; BMI 31.4 ± 3.1 kg/m2) was conducted in participants with metabolic syndrome. After baseline assessments, an energy-dense drink (969 Kcals, 64.5 g fat, 84.5 g carbohydrate, 17.9 g protein) was consumed with either 26 g (freeze-dried) blueberries (equivalent to 1 cup/150 g fresh blueberries) or 26 g isocaloric matched placebo. Repeat blood samples (30, 60, 90, 120, 180, 360 min and 24 h), a 24 h urine collection and vascular measures (at 3, 6, and 24 h) were performed. Insulin and glucose, lipoprotein levels, endothelial function (flow mediated dilatation (FMD)), aortic and systemic arterial stiffness (pulse wave velocity (PWV), Augmentation Index (AIx) respectively), blood pressure (BP), and anthocyanin metabolism (serum and 24 h urine) were assessed. RESULTS: Blueberries favorably affected postprandial (0-24 h) concentrations of glucose (p < 0.001), insulin (p < 0.01), total cholesterol (p = 0.04), HDL-C, large HDL particles (L-HDL-P) (both p < 0.01), extra-large HDL particles (XL-HDL-P; p = 0.04) and Apo-A1 (p = 0.01), but not LDL-C, TG, or Apo-B. After a transient higher peak glucose concentration at 1 h after blueberry intake ([8.2 mmol/L, 95%CI: 7.7, 8.8] vs placebo [6.9 mmol/L, 95%CI: 6.4, 7.4]; p = 0.001), blueberries significantly attenuated 3 h glucose ([4.3 mmol/L, 95%CI: 3.8, 4.8] vs placebo [5.1 mmol/L, 95%CI: 4.6, 5.6]; p = 0.03) and insulin concentrations (blueberry: [23.4 pmol/L, 95%CI: 15.4, 31.3] vs placebo [52.9 pmol/L, 95%CI: 41.0, 64.8]; p = 0.0001). Blueberries also improved HDL-C ([1.12 mmol/L, 95%CI: 1.06, 1.19] vs placebo [1.08 mmol/L, 95%CI: 1.02, 1.14]; p = 0.04) at 90 min and XL-HDLP levels ([0.38 × 10-6, 95%CI: 0.35, 0.42] vs placebo [0.35 × 10-6, 95%CI: 0.32, 0.39]; p = 0.02) at 3 h. Likewise, significant improvements were observed 6 h after blueberries for HDL-C ([1.17 mmol/L, 95%CI: 1.11, 1.24] vs placebo [1.10 mmol/L, 95%CI: 1.03, 1.16]; p < 0.001), Apo-A1 ([1.37 mmol/L, 95%CI: 1.32, 1.41] vs placebo [1.31 mmol/L, 95%CI: 1.27, 1.35]; p = 0.003), L-HDLP ([0.70 × 10-6, 95%CI: 0.60, 0.81] vs placebo [0.59 × 10-6, 95%CI: 0.50, 0.68]; p = 0.003) and XL-HDLP ([0.44 × 10-6, 95%CI: 0.40, 0.48] vs placebo [0.40 × 10-6, 95%CI: 0.36, 0.44]; p < 0.001). Similarly, total cholesterol levels were significantly lower 24 h after blueberries ([4.9 mmol/L, 95%CI: 4.6, 5.1] vs placebo [5.0 mmol/L, 95%CI: 4.8, 5.3]; p = 0.04). Conversely, no effects were observed for FMD, PWV, AIx and BP. As anticipated, total anthocyanin-derived phenolic acid metabolite concentrations significantly increased in the 24 h after blueberry intake; especially hippuric acid (6-7-fold serum increase, 10-fold urinary increase). In exploratory analysis, a range of serum/urine metabolites were associated with favorable changes in total cholesterol, HDL-C, XL-HDLP and Apo-A1 (R = 0.43 to 0.50). CONCLUSIONS: For the first time, in an at-risk population, we show that single-exposure to the equivalent of 1 cup blueberries (provided as freeze-dried powder) attenuates the deleterious postprandial effects of consuming an energy-dense high-fat/high-sugar meal over 24 h; reducing insulinaemia and glucose levels, lowering cholesterol, and improving HDL-C, fractions of HDL-P and Apo-A1. Consequently, intake of anthocyanin-rich blueberries may reduce the acute cardiometabolic burden of energy-dense meals. CLINICAL TRIAL REGISTRY: NCT02035592 at www.clinicaltrials.gov.

Dietary intake of cyanidin-3-glucoside induces a long-lasting cardioprotection from ischemia/reperfusion injury by altering the microbiota.

The anthocyanin class of flavonoids, including cyanidin-3-glucoside (C3G) present in berries, blood oranges and pigmented cereal crops, are food bioactives with antioxidant and anti-inflammatory action, capable to reduce myocardial ischemia/reperfusion (I/R) injury by unclear mechanism. Assessing the value of sporadic beneficial diet is critical for practical application. We aimed to determine whether and how the cardioptotective effect of dietary intake of anthocyanins persists. Gene expression, histology and resistance to I/R were investigated ex vivo in hearts from mice after a month beyond the cease of the C3G-enriched diet. Cardiac injury, oxidative stress and mitochondrial damage following I/R was effectively reduced in mice fed C3G-enriched diet, even after a month of wash out with standard diet. Cardioprotection was observed also in immune-deficient mice lacking mature B and T cells indicating the anti-inflammatory activity of C3G was not involved. Moreover, the transcription reprogramming induced by the C3G-enriched diets was rescued by the wash out treatment. Instead, we found C3G-enriched diet changed the microbiome and the transplantation of the fecal microbiota transferred the cardioprotection from mice fed C3G-enriched diet to mice fed standard diet. These findings established the effect of C3G dietary intake on gut microbiota determines long lasting cardioprotection.

Rosinidin Attenuates Lipopolysaccharide-Induced Memory Impairment in Rats: Possible Mechanisms of Action Include Antioxidant and Anti-Inflammatory Effects.

The investigation aimed to evaluate the favourable effects of rosinidin in lipopolysaccharide (LPS)-induced learning and memory impairment in rats. Adult Wistar rats (150-200 g) were segregated equally into four different groups and treated as below: Group 1 (normal) and Group 2 (LPS control) were administered orally with 3 mL of 0.5% SCMC (vehicle); Group 3 and Group 4 were test groups and orally administered with rosinidin lower dose (10 mg/kg) and higher dose 20 mg/kg. Daily, 1 h post-offer mentioned treatments, Group 1 animals were injected with normal saline (i.p.) and groups 2-4 were treated with 1 mg/kg/day of LPS. This treatment schedule was followed daily for 7 days. During the treatment, schedule rats were evaluated for spontaneous locomotor activity, memory, and learning abilities. The biochemical assessment was carried out of acetylcholine esterase (AChE), endogenous antioxidants (GSH, SOD, GPx, and catalase), oxidative stress marker MDA, neuroinflammatory markers (IL-6, IL-1ß, TNF-α, and NF-κB), and BDNF. LPS-induced reduced spontaneous locomotor activity and memory impairment in the animals. Moreover, LPS reduced GSH, SOD, GPx, and catalase levels; altered activities of AChE; elevated levels of MDA, IL-6, IL-1ß, TNF-α, and NF-κB; and attenuated the levels of BDNF in brain tissue. Administration of rosinidin to LPS-treated animals significantly reduced LPS-induced neurobehavioral impairments, oxidative stress, neuroinflammatory markers, and reversed the Ach enzyme activities and BDNF levels towards normal. Results demonstrated that rosinidin attenuates the effects of LPS on learning memory in rats.

Enhancement of the Anti-Angiogenic Effects of Delphinidin When Encapsulated within Small Extracellular Vesicles.

(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-ß-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.

Jabuticaba (Myrciaria jaboticaba) Peel as a Sustainable Source of Anthocyanins and Ellagitannins Delivered by Phospholipid Vesicles for Alleviating Oxidative Stress in Human Keratinocytes.

The Brazilian berry scientifically known as jabuticaba is a fruit covered by a dark purple peel that is still rich in bioactives, especially polyphenols. Considering that, this work was aimed at obtaining an extract from the peel of jabuticaba fruits, identifying its main components, loading it in phospholipid vesicles specifically tailored for skin delivery and evaluating their biological efficacy. The extract was obtained by pressurized hot water extraction (PHWE), which is considered an easy and low dissipative method, and it was rich in polyphenolic compounds, especially flavonoids (ortho-diphenols and condensed tannins), anthocyanins (cyanidin 3-O-glucoside and delphinidin 3-O-glucoside) and gallic acid, which were responsible for the high antioxidant activity detected using different colorimetric methods (DPPH, FRAP, CUPRAC and metal chelation). To improve the stability and extract effectiveness, it was incorporated into ultradeformable phospholipid vesicles (transfersomes) that were modified by adding two different polymers (hydroxyethyl cellulose and sodium hyaluronate), thus obtaining HEcellulose-transfersomes and hyaluronan-transfersomes. Transfersomes without polymers were the smallest, as the addition of the polymer led to the formation of larger vesicles that were more stable in storage. The incorporation of the extract in the vesicles promoted their beneficial activities as they were capable, to a greater extent than the solution used as reference, of counteracting the toxic effect of hydrogen peroxide and even of speeding up the healing of a wound performed in a cell monolayer, especially when vesicles were enriched with polymers. Given that, polymer enriched vesicles may represent a good strategy to produce cosmetical and cosmeceutical products with beneficial properties for skin.

Impact of short-term oral dose of cinnamtannin A2, an (-)-epicatechin tetramer, on spatial memory and adult hippocampal neurogenesis in mouse.

Recent epidemiological and intervention studies have suggested that polyphenol-rich plant food consumption reduced the risk of cognitive decline. However, the findings were tentative and by no means definitive. In the present study, we examined the impact of short-term oral administration of cinnamtannin A2 (A2), an (-)-epicatechin tetramer, on adult hippocampal neurogenesis and cognitive function in mice. Mice received supplementation with vehicle (20% glycerol) or 100 µg/kg A2 for 10 days. Then, we conducted the open field test, the object location test, and the novel object test. In the open field test, the A2-treated group tended to spend more time in the center of the arena, compared to the vehicle-treated group. The A2-treated group spent significantly more time exploring objects placed in different locations, compared to the vehicle-treated group. There were no significant differences between groups in the object preference index or in the novel object test. In addition, A2 administration significantly increased the number of hippocampal bromodeoxyuridine-labeled cells in the dentate gyrus, but not in the CA1 or CA3 regions. These results suggested that short-term administration of A2 may impact spatial memory by enhancing neurogenesis in the dentate gyrus of adult mice.

Metformin and cyanidin 3-O-galactoside from Aronia melanocarpa synergistically alleviate cognitive impairment in SAMP8 mice.

Cyanidin 3-O-galactoside (Cy3Gal) from Aronia melanocarpa has been reported to alleviate cognitive impairment. Metformin for preventing the neurodegenerative disease is attracting increasing attention. However, the neuroprotective and metabolic health promoting both of their effects are not clear. We chose the senescence accelerated mouse prone 8 (SAMP8) as a model of spontaneous learning and memory impairment. This study aimed to investigate the synergistic neuroprotective effect of metformin and Cy3Gal by behavioral and histopathological assays and metabolite analysis in SAMP8 mice. The SAMR1 mice were the normal group, and the SAMP8 mice were divided into five groups, including the SAMP8 model group, the donepezil (1 mg kg-1, ig) group, the metformin (100 mg kg-1, ig) group, the Cy3Gal (25 mg kg-1, ig) group, and the combination of metformin plus Cy3Gal (Met + Cy3Gal, 100 mg kg-1, 25 mg kg-1, ig) group. The behavior experiments showed that the SAMP8 mice treated with metformin and Cy3Gal showed improved spatial learning and memory compared to the SAMP8 model group. The number of neurons in the Met + Cy3Gal group was significantly higher than that in the SAMP8 group and the Met + Cy3Gal group showed significantly reduced Aß aggregation in the brain, which was elevated in SAMP8 mice. Compared with SAMP8 mice, the Met + Cy3Gal group showed decreased indole, methyl esters and ketones and increased short-chain fatty acids and alcohols in feces and urine by regulating the fatty acid biosynthesis and degradation. This study confirmed the neuroprotective effects of coadministration of metformin and cyanidin 3-O-galactoside in the SAMP8 mice, and suggested its positive effect on postponing the progression of Alzheimer's disease.

Anthocyanins in Lycium ruthenicum Murray reduce nicotine withdrawal-induced anxiety and craving in mice.

Lycium ruthenicum Murray is widely used in traditional Chinese medicine and is believed to have antimicrobial, antioxidant, and anti-fatigue effects. Anthocyanins are considered to be one of the main active components. The previous work by our research team found that the anthocyanins in Lycium ruthenicum extract (ALRM) produce a stable anti-anxiety effect. The mechanisms of action include reducing the level of corticotropin-releasing factor (CRF) as well as regulating extracellular signal-regulated kinase/mitogen activation, protein kinase (ERK/MAPK) pathways, and others, all of which are related to the mechanisms of nicotine addiction. To investigate the effects of ALRM on anxiety and craving behavior after nicotine withdrawal, the components of ALRM were analyzed using the UPLC-Orbitrap MS method. The effects of ALRM on anxiety behavior induced by nicotine withdrawal were investigated in mice using the elevated plus maze (EPM) and light-dark box (LDB) tests. The effects of ALRM on craving behavior after nicotine withdrawal were further investigated using the conditional place preference (CPP) test. The EPM and LDB tests demonstrated that ALRM could alleviate the anxiety behavior induced by nicotine withdrawal and reduce nicotine craving in mice. Based on the identified ALRM components, the network pharmacology method was used to predict the mechanism of ALRM alleviating anxiety after nicotine withdrawal in mice. It was speculated that ALRM was involved in the production and transmission of dopamine, choline, and other nervous system functions and exhibited a potential role in treating nicotine addiction.

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

BACKGROUND: Dyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia. METHODS: A double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks. FINDINGS: Compared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) (P < 0.05). Moreover, compared to placebo group, anthocyanins at 320 mg/day inhibited collagen-induced platelet aggregation (-7.05±2.38%), ADP-induced platelet aggregation (-7.14±2.00%), platelet ROS levels (-14.55±1.86%), and mitochondrial membrane potential (7.40±1.56%) (P < 0.05). There were dose-response relationships between anthocyanins and the attenuation of platelet aggregation, mitochondrial membrane potential and ROS levels (P for trend <0.05). Furthermore, significantly positive correlations were observed between changes in collagen-induced (r = 0.473) or ADP-induced (r = 0.551) platelet aggregation and ROS levels in subjects with dyslipidemia after the 12-week intervention (P < 0.05). INTERPRETATION: Anthocyanin supplementation dose-dependently attenuates platelet function, and 12-week supplementation with 80 mg/day or more of anthocyanins can reduce platelet function in individuals with dyslipidemia. FUNDING: None.

Effects of Berry Anthocyanins on Cognitive Performance, Vascular Function and Cardiometabolic Risk Markers: A Systematic Review of Randomized Placebo-Controlled Intervention Studies in Humans.

Supplementation with anthocyanins, which are a type of flavonoids mainly found in various berries, is hypothesized to be a promising approach to lower the risk of developing cognitive decline. The aim of this systematic review was to provide a comprehensive overview of dietary intervention trials describing effects of berry anthocyanins on cognitive performance in humans, while also addressing potential underlying mechanisms. A total of 1197 articles were identified through a systematic search, and 49 studies reporting effects on cognitive performance (n = 18), vascular function (n = 22), or cardiometabolic risk markers (n = 32) were included. Significant improvements were observed on memory, while some of the studies also reported effects on attention and psychomotor speed or executive function. Vascular function markers such as brachial artery flow-mediated vasodilation were also affected and consistent evidence was provided for the beneficial effects of berry anthocyanins on endothelial function. Finally, studies reported improvements in blood pressure, but effects on metabolic risk markers (e.g. carbohydrate and lipid metabolism) were less consistent. In conclusion, this review provides evidence for the beneficial effects of berry anthocyanins on cognitive performance as memory improved. Whether observed anthocyanin-induced improvements in vascular function and blood pressure underlie beneficial effects on cognitive performance warrants further study.

Comparative Analysis of Histone H3K4me3 Distribution in Mouse Liver in Different Diets Reveals the Epigenetic Efficacy of Cyanidin-3-O-glucoside Dietary Intake.

BACKGROUND: Different diets result in significantly different phenotypes through metabolic and genomic reprogramming. Epigenetic marks, identified in humans and mouse models through caloric restriction, a high-fat diet or the intake of specific bioactives, suggest that genomic reprogramming drives this metabolic reprogramming and mediates the effect of nutrition on health. Histone modifications encode the epigenetic signal, which adapts genome functions to environmental conditions, including diets, by tuning the structure and properties of chromatin. To date, the effect of different diets on the genome-wide distribution of critical histone marks has not been determined. METHODS: Using chromatin immunoprecipitation sequencing, we investigated the distribution of the trimethylation of lysine 4 of histone H3 in the liver of mice fed for one year with five different diets, including: chow containing yellow corn powder as an extra source of plant bioactives or specifically enriched with cyanidin-3-O-Glucoside, high-fat-enriched obesogenic diets, and caloric-restricted pro-longevity diets. CONCLUSIONS: Comparison of the resulting histone mark profiles revealed that functional food containing cyanidin determines a broad effect.

Effects of Anthocyanin Supplementation on Reduction of Obesity Criteria: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Anthocyanins, water-soluble flavonoids that produce red-to-blue pigment in plants, have antioxidant properties and have been developed as a functional food to fight obesity. In randomized controlled trials (RCTs), a systematic review with meta-analysis (SR-MA) was used to investigate these anti-obesity effects. Using search engines (PubMed, EMBASE, Cochrane-library, and CINAHL) and keywords (anthocyanins, BMI, WC, WHR, and inflammatory biomarkers), 11 out of 642 RCTs (28.3-500 mg/day of anthocyanins for 4 to 24 weeks) were included. The results showed a significant reduction in body mass index (BMI) (MD = -0.36, 95% CI = -0.58 to -0.13), but body weight (BW) and waist circumference (WC) did not change. Anthocyanins decreased BMI in the non-obese (non-OB) group in five RCTs (BMI ≤ 25; MD = -0.40 kg/m2; 95% CI = -0.64 to -0.16;) but did not affect BMI in the obese (OB) group. A subgroup analysis of six RCTs showed that fewer than 300 mg/day reduced BMI (MD = -0.37; 95% CI = -0.06 to -0.14), but ≥300 mg/day did not. A treatment duration of four weeks for four RCTs was sufficient to decrease the BMI (MD = -0.41; 95% CI = -0.66 to -0.16) as opposed to a longer treatment (6-8 or ≥12 weeks). An analysis of the effect of anthocyanins on the BMI showed a significant fall among those from the Middle East compared to those from Asia, Europe, South America, or Oceania. In conclusion, the anthocyanin supplementation of 300 mg/day or less for four weeks was sufficient to reduce the BMI and BW compared to the higher-dose and longer-treatment RCTs. However, further studies might be conducted regarding the dose- or period-dependent responses on various obese biomarkers.

Metformin in Combination with Malvidin Prevents Progression of Non-Alcoholic Fatty Liver Disease via Improving Lipid and Glucose Metabolisms, and Inhibiting Inflammation in Type 2 Diabetes Rats.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of chronic liver disease and is closely linked to insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. However, no effective drug therapies have been approved to treat this disease. The present research aimed to evaluate the therapeutic effects of the combination of oral hypoglycemic drug metformin (MET) and a natural product malvidin (MAL) on hepatic damage in HFD/STZ-induced diabetic rats. METHODS: Sprague-Dawley rats were divided into five groups: normal control group (NC), diabetic control group (DC), DC+MET group, DC+MAL group, and DC+MET+MAL group and treated for eight weeks. Blood and liver tissue samples were collected for metabolic parameters, histological, and RT-qPCR analysis. RESULTS: Our findings indicated that hyperglycemia, insulin resistance, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) in diabetic rats were alleviated after oral treatment with MET and MAL, particularly their combination therapy. Besides, the expression of SREBP-1c, ACC, FAS, IL-6, IL-8, and NF-κB mRNA was down-regulated by MET+MAL, and the expression of PPARα, CPT1, and LPL was up-regulated by MET+MAL. CONCLUSION: The evidence of this research indicated that the combination therapy may represent an efficient strategy against NAFLD in T2DM rats via improving lipid and glucose metabolisms, and inhibiting inflammation.

Metabolic Fate and Cardiometabolic Effects of Phenolic Compounds from Red-Fleshed Apple in Hypercholesterolemic Rats: A Comparative Study with Common White-Fleshed Apple. The AppleCOR Study.

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats.