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.

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.

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.

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.

Purple grumixama anthocyanins (Eugenia brasiliensis Lam.) attenuate obesity and insulin resistance in high-fat diet mice.

Some polyphenols have been reported to modulate the expression of several genes related to lipid metabolism and insulin signaling, ameliorating metabolic disorders. We investigated the potential for the polyphenols of two varieties of grumixama, the purple fruit rich in anthocyanins and the yellow fruit, both also rich in ellagitannins, to attenuate obesity-associated metabolic disorders. Mice were fed a high fat and high sucrose diet, supplemented daily with yellow and purple extracts (200 mg per kg of body weight) for eight weeks. Purple grumixama supplementation was found to decrease body weight gain, improve insulin sensitivity and glucose-induced hyperinsulinemia, and reduce hepatic triglyceride accumulation. A decrease in intrahepatic lipids in mice treated with the purple grumixama extract was associated with lipid metabolism modulation by the PPAR signaling pathway. LPL, ApoE, and LDLr were found to be down-regulated, while Acox1 and ApoB were found to be upregulated. Some of these genes were also modulated by the yellow extract. In addition, both extracts decreased oGTT and plasma LPS. The results were associated with the presence of phenolic acids and urolithins. In conclusion, most likely the anthocyanins from the purple grumixama phenolic extract is responsible for reducing obesity and insulin resistance.

Anthocyanins from the fruits of Lycium ruthenicum Murray improve high-fat diet-induced insulin resistance by ameliorating inflammation and oxidative stress in mice.

A high-fat diet (HFD) promotes tissue inflammation, oxidative stress and insulin resistance (IR), thereby contributing to the development of obesity and diabetes. Anthocyanins from Lycium ruthenicum (AC) have demonstrated anti-obesity effects and modulated IR. To investigate the mechanism by which AC attenuates the adverse effects of consuming a HFD, C57BL/6J mice were fed a HFD supplemented with AC or a control diet without AC for 12 weeks. AC supplementation decreased the amount of weight gain, hepatic lipid, and sequentially improved dyslipidemia, inflammation, oxidative stress, and IR in HFD-fed mice. Molecular data revealed that AC inhibited hepatic inflammation by reducing TLR4/NF-κB/JNK in the liver tissues and ameliorated oxidative stress by activating the Nrf2/HO-1/NQO1 pathway. Thus, AC might activate IRS-1/AKT and prevent HFD-induced gluconeogenesis and IR by ameliorating inflammation and oxidative stress. Modulation of inflammation and oxidative stress with AC may represent a promising target for the treatment of IR and provide insight into the mechanism by which AC protects against obesity.

Nanoencapsulation in low-molecular-weight chitosan improves in vivo antioxidant potential of black carrot anthocyanin.

BACKGROUND: Anthocyanins are flavonoids that are potential antioxidant, anti-inflammatory, anti-obesity, and anti-carcinogenic nutraceutical ingredients. However, low chemical stability and low bioavailability limit the use of anthocyanins in food. Nanoencapsulation using biopolymers is a recent successful strategy for stabilization of anthocyanins. This study reports the development, characterization, and antioxidant activity of black carrot anthocyanin-loaded chitosan nanoparticles (ACNPs). RESULTS: The ionic gelation technique yielded the ACNPs. The mean hydrodynamic diameter d and polydispersity index PDI of chitosan nanoparticles and ACNPs were found to be d = 455 nm and PDI = 0.542 respectively for chitosan nanoparticles and d = 274 nm and PDI = 0.376 respectively for ACNPs. The size distribution was bimodal. The surface topography revealed that the ACNPs are spherical and display a coacervate structure. Fourier transform infrared analysis revealed physicochemical interactions of anthocyanins with chitosan. The loading process could achieve an encapsulation efficiency of 70%. The flow behavior index η of encapsulated ACNPs samples revealed Newtonian and shear thickening characteristics. There was a marginal reduction in the in vitro antioxidant potential of anthocyanins after nanoencapsulation, as evidenced from 2,2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. Interestingly, the in vivo antioxidant potential of anthocyanins improved following nanoencapsulation, as observed in the serum antioxidant assays. CONCLUSION: The optimized nanoencapsulation process resulted in spherical nanoparticles with appreciable encapsulation efficiency. The nanoencapsulation process improved the in vivo antioxidant activity of anthocyanins, indicating enhanced stability and bioavailability. The promising antioxidant activity of the ACNPs suggests a potential for utilization as a nutraceutical supplement. © 2021 Society of Chemical Industry.

Blueberry supplementation reduces the blood lactate response to running in normobaric hypoxia but has no effect on performance in recreational runners.

BACKGROUND: Blueberries are concentrated with anthocyanins possessing antioxidant properties. As these properties counter fatigue, blueberry supplementation may improve performance and recovery, particularly in hypoxia, where oxidative stress is elevated. METHODS: This study examined the effects of blueberry supplementation on running performance, physiological responses, and recovery in normobaric hypoxia. Eleven experienced runners completed a 30-minute time-trial (TT) in normobaric hypoxia (%O2 = 15.5 %) on separate days after supplementation with four days of blueberries (BLU) or four days of placebo (PLA). Heart rate (HR), oxygen saturation (SaO2) and ratings of perceived exertion (RPE) were monitored during the TT. Blood lactate and fraction of exhaled nitric oxide (FENO) were assessed pre-TT, post-TT, and during recovery. RESULTS: No significant differences were observed in the distance run during the TT, HR, SaO2, and RPE. The post-TT increase in blood lactate was significantly lower in BLU than PLA (p = 0.036). Pre-TT and post-TT FENO did not differ between conditions. Blood lactate recovery following the TT was similar between conditions. CONCLUSIONS: Four days of blueberry supplementation did not alter running performance or cardiovascular and perceptual responses in normobaric hypoxia. Supplementation lowered the blood lactate response to running, however, the significance of this finding is uncertain given the absence of an ergogenic effect.

Effect of Hydrolysable Tannins and Anthocyanins on Recurrent Urinary Tract Infections in Nephropathic Patients: Preliminary Data.

Urinary tract infections (UTIs) are caused by uropathogenic microorganism colonization. UTIs often require an antibiotic therapy that can cause the selection of antibiotic-resistant bacterial strains. A natural bioactive compound may represent a valid therapeutic adjuvant approach, in combination with drug therapy. In this paper, we present a pilot study, based on the administration of an oral food supplement (OFS), containing chestnut tannins and anthocyanins, to nephropathic patients suffering from recurrent UTIs (16 treated patients with 1 cp/day and 10 untreated patients). We performed laboratory tests and quality of life and body composition assessments, at T0 (baseline) and T1 (after 6 weeks OFS assumption). The analysis of OFS was performed by HPLC-DAD-MS for its content in polyphenols and by in vitro tests for its antioxidative and anti-free radical activities. In each capsule, polyphenol content was 6.21 mg (4.57 mg hydrolysable tannins, 0.94 mg anthocyanosides, 0.51 mg proanthocyanidins, 0.18 mg quercetin derivatives). A significant reduction of erythrocyte sedimentation rate was observed only in male patients. Urinalysis showed a significant reduction of leukocytes in both genders, whereas urinary bacterial flora at T1 significantly decreased only in male subjects. Tannins seem to exert an antimicrobial action according to gender, useful to counteract the recurrence of UTIs.

Potential of anthocyanin as an anti-inflammatory agent: a human clinical trial on type 2 diabetic, diabetic at-risk and healthy adults.

OBJECTIVE: The present research aimed to investigate the anti-inflammatory potential of dietary anthocyanin (ACN) in type 2 diabetic (T2D), T2D-at-risk and healthy individuals. Furthermore, dietary inflammatory index (DII) was used to study the association of diet with biomarkers of inflammation. RESEARCH METHODS: An open-label clinical trial was conducted at Griffith University investigating the efficacy of 320 mg ACN supplementation per day over the course of 4 weeks. Diabetes-associated inflammatory biomarkers and relevant biochemical and physical parameters were tested pre-and post-intervention, and participants' dietary inflammatory potential was estimated. RESULTS: A significant reduction in the pro-inflammatory biomarkers' interleukin-6, interleukin-18, and tumour necrosis factor-α was observed in the T2D group. In addition, some, but not all, biochemical parameters including fasting blood glucose, low-density lipoprotein cholesterol and uric acid were significantly improved in T2D-at-risk group. Moreover, a significant difference was detected between the DII scores of the healthy and T2D groups. DII score for the T2D group was consistent with an anti-inflammatory diet. CONCLUSION: Anti-inflammatory potential of dietary ACN in T2D participants was evidenced in the present study. Although, anti-inflammatory dietary patterns of T2D participants may have accelerated the anti-inflammatory effect of the ACN capsules supplemented in this trial.

Purified anthocyanins from Zea mays L. cob ameliorates chronic liver injury in mice via modulating of oxidative stress and apoptosis.

BACKGROUND: Purple corn (Zea mays L.) is one of the main economic crops in China and has been used in the treatment of cystitis, urinary infections and obesity. However, purple corncobs, the by-product remaining after processing and having an intense purple-black color, are normally disposed of as waste or used as animal feed. Therefore, to further expand the medicinal value of purple corncob, its content was analyzed and, after purification, the effect and mechanism of purified purple corncob anthocyanins (PPCCA) on CCl4 -induced chronic liver injury in mice were investigated. RESULTS: It was observed that the total anthocyanin content (TAC) from PPCCA (317.51 ± 9.30 mg cyanidin 3-O-glucoside (C-3-G) g-1 dry weight) was significantly higher than that from the purified purple corn seed anthocyanin (266.73 ± 3.67 mg C-3-G g-1 dry weight), of which C-3-G accounted for 90.6% and 90.4% of the TAC, respectively. Furthermore, compared with the CCl4 group, PPCCA treatment significantly reduced liver index, serum total bilirubin, alanine transaminase, aspartate transaminase and liver malondialdehyde levels, but increased liver superoxide dismutase activity. The pathological changes were also improved, such as more regular arrangement of hepatocytes, less swelling, and fewer vacuoles and apoptotic cells. Additionally, mechanistic studies showed that PPCCA downregulated the expression of Caspase-3, Bax and cytochrome P450 2E1 proteins in the liver and upregulated the expression of Bcl-2. CONCLUSION: These results demonstrated that PPCCA could ameliorate CCl4 -induced chronic liver injury by regulating oxidative stress and hepatocyte apoptosis pathways. © 2021 Society of Chemical Industry.

Improving the physicochemical stability and functionality of nanoliposome using green polymer for the delivery of pelargonidin-3-O-glucoside.

This study aimed to improve the physicochemical stability of nanoliposome (NL) with enhanced functionality for the delivery of Pelargonidin-3-O-glucoside (P3G) using biopolymers, i.e. chitosan (CH) and pectin (P). In this study, we successfully developed stabilized liposomal carriers, i.e. CH-conjugated NL (CH-NL) and P-conjugated CH-NL (P-CH-NL) using an optimum concentration of CH (0.6 wt%) and P (0.5 wt%). Results revealed that P-CH-NL had better physical stability to salt and pH with maximum P3G retention (>97%) under oxidative, thermal, and UV conditions. Nanoliposomes were more stable under refrigerated-storage and ensured high P3G retention (>96%). In vitro mucoadhesion study revealed that CH-NL had better mucin adsorption efficiency (59.72%) followed by P-CH-NL and NL. Furthermore, CH-NL and P-CH-NL alternatively had better stability to serum than NL. Taken together, the stabilization of nanoliposome using chitosan and pectin can be a promising approach for the delivery of hydrophilic compounds in association with enhanced stability and functionality.

Skin toxicity following radiotherapy in patients with breast carcinoma: is anthocyanin supplementation beneficial?

BACKGROUND: The EU-supported ATHENA project stems from a previous study suggesting that moderate wine consumption reduced the side-effects of radiotherapy (RT) in breast cancer patients, an effect possibly due to non-alcoholic anthocyanin fractions of wine. OBJECTIVE: To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients. METHODS: Randomized, controlled, double-blind clinical trial. Patients were assigned to an intensity modulated radiation therapy (IMRT) either for three or five weeks, then randomized to receive three times a day a water-soluble anthocyanin (125 mg)-rich extract of corn cob or a placebo. Supplementation started one week before till the end of RT. Skin characteristics were detected by a standardized, non-invasive Cutometer® dual-MPA580, providing quantitative indices of skin maximal distensibility (R0), elasticity (R2, R5, R7) and viscoelasticity (R6); a Mexameter® MX18 probe evaluated the skin erythema (Er) and melanin (M). Measures were performed before (T0), at the end of RT and of supplementation (T1), and 1, 6 and 12 months after RT (T2-T4). Acute and late skin toxicity were scored according to the RTOG/EORTG scale. Selected biomarkers were measured at T0 and T1. RESULTS: 193 patients previously assigned to 3- or 5-week RT schedules were randomized to either anthocyanin (97) or placebo (96) supplementation. RT induced changes in skin parameters: R0, R2, R5 and R7 decreased, while R6 increased; the changes in R0 and R6 continued in the same direction up to one year, while the others recovered towards basal values; Er and M peaked at T1 and T2, respectively, and returned to basal values at T4. Comparable skin changes were apparent in anthocyanin and placebo groups. A moderate RT-induced increase in total and HDL cholesterol and triglycerides was prevented by anthocyanins. CONCLUSIONS: Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe.

Anthocyanins attenuate vascular and inflammatory responses to a high fat high energy meal challenge in overweight older adults: A cross-over, randomized, double-blind clinical trial.

BACKGROUND & AIMS: Postprandial metabolic imbalances are important indicators of later developing cardiovascular disease (CVD). This study investigated the effects of food anthocyanins on vascular and microvascular function, and CVD associated biomarkers following a high fat high energy (HFHE) meal challenge in overweight older adults. METHODS: Sixteen subjects (13 female, 3 male, mean age 65.9 SD 6.0 and body mass index 30.6 kg/m2 SD 3.9) participated in a crossover, randomized, controlled, double-blind clinical trial (registered under Australian New Zealand Clinical Trials Registry, identifier no. ACTRN12620000437965). Participants consumed a HFHE meal with a 250 mL dose of either intervention (anthocyanins-rich Queen Garnet Plum) or control (apricot) juice. Blood samples and blood pressure measures were collected at baseline, 2 h and 4 h following the HFHE meal. Vascular and microvascular function were evaluated at baseline and 2 h after the HFHE meal. RESULTS: Participants had a higher 2 h postprandial flow-mediated dilatation (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P = 0.019 and P = 0.049, respectively). C-reactive protein was lower 4 h postprandially in the anthocyanins (1.80 mg/L, IQR 0.90) vs control arm (2.30 mg/L, IQR 1.95) (P = 0.026), accompanied by a trend for lower concentrations of interleukin-6 (P = 0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor alpha, interleukin-1 beta, or maximum microvascular perfusion following iontophoresis of acetylcholine. CONCLUSION: Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat 'Western' meal. Further studies are required to better elucidate the clinical implications of postprandial biomarkers of CVD.

Stabilization of Delphinidin in Complex with Sulfobutylether-ß-Cyclodextrin Allows for Antinociception in Inflammatory Pain.

Aims: Delphinidin (DEL) is a plant-derived antioxidant with clinical potential to treat inflammatory pain but suffers from poor solubility and low bioavailability. The aim of the study was to develop a well-tolerated cyclodextrin (CD)-DEL complex with enhanced bioavailability and to investigate the mechanisms behind its antinociceptive effects in a preclinical model of inflammatory pain. Results: CD-DEL was highly soluble and stable in aqueous solution, and was nontoxic. Systemic administration of CD-DEL reversed mechanical and heat hyperalgesia, while its local application into the complete Freund's adjuvant (CFA)-induced inflamed paw dose-dependently reduced mechanical hyperalgesia, paw volume, formation of the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE), and tissue migration of CD68+ macrophages. CD-DEL also directly prevented 4-HNE-induced mechanical hyperalgesia, cold allodynia, and an increase in the intracellular calcium concentration into transient receptor potential ankyrin 1 expressing cells. Both 4-HNE- and CFA-induced reactive oxygen species (ROS) levels were sensitive to CD-DEL, while its capacity to scavenge superoxide anion radicals (inhibitory concentration 50 [IC50]: 70 ± 5 µM) was higher than that observed for hydroxyl radicals (IC50: 600 ± 50 µM). Finally, CD-DEL upregulated heme oxygenase 1 that was prevented by HMOX-1 siRNA in vitro. Innovation:In vivo application of DEL to treat inflammatory pain is facilitated by complexation with CD. Apart from its antioxidant effects, the CD-DEL has a unique second antioxidative mechanism involving capturing of 4-HNE into the CD cavity followed by displacement and release of the ROS scavenger DEL. Conclusion: CD-DEL has antinociceptive, antioxidative, and anti-inflammatory effects making it a promising formulation for the local treatment of inflammatory pain.

Intake Duration of Anthocyanin-Rich New Zealand Blackcurrant Extract Affects Metabolic Responses during Moderate Intensity Walking Exercise in Adult Males.

We examined effects of intake duration of anthocyanin-rich New Zealand blackcurrant (NZBC) extract on physiological and metabolic responses during moderate intensity walking. Healthy men (n = 16, age: 24 ± 6 years, body mass: 78 ± 16 kg, BMI: 24.7 ± 4.1 kg·m-2, body fat: 15 ± 5%) volunteered. One metabolic equivalent (1-MET: 3.95 ± 0.64 ml·kg-1·min-1) was measured during supine rest. Responses during the 30-min walk (n = 3: 4-MET; n = 13: 5-MET) (speed: 5.7 ± 0.7 km·hr-1) were measured at 7-10, 17-20 and 27-30 min and averaged over the time periods. For intake conditions (7-days and 14-days), two capsules of NZBC extract (600 mg containing 210 mg of anthocyanins) were taken with breakfast (14-day washout). The final two capsules were ingested 2-hr before the morning walk. Intake duration of NZBC extract had no effect on heart rate, minute ventilation, oxygen uptake, and carbon dioxide production. Fat oxidation was enhanced with 7- and 14-day intake by 11 ± 19% and 17 ± 26% (baseline: 0.36 ± 0.12, 7-day: 0.39 ± 0.13, 14-day: 0.41 ± 0.13 g·min-1, p = 0.007). Only 14-day intake lowered RER (baseline: 0.852 ± 0.046, 7-day: 0.843 ± 0.045, 14-day: 0.837 ± 0.037, p = 0.019) and carbohydrate oxidation (baseline: 0.95 ± 0.40, 7-day: 0.91 ± 0.40, 14-day: 0.86 ± 0.33 g·min-1, p = 0.032). Rating of perceived exertion was lower with 7-day and 14-day intake (baseline: 11.0 ± 2.3, 7-day: 10.5 ± 1.8, 14-day: 10.3 ± 2.1, p = 0.002). Longer intake duration (i.e. 14 days) of New Zealand blackcurrant extract seems to enhance fat oxidation more during a 30-min moderate intensity walk than 7 days intake. The intake duration of anthocyanin-rich New Zealand blackcurrant extract may be due to an enhanced bioavailability of anthocyanin-derived metabolites that alter the mechanisms for substrate oxidation during moderate intensity exercise.

Matrix-assisted laser desorption/ionization mass spectrometry-guided visualization analysis of intestinal absorption of acylated anthocyanins in Sprague-Dawley rats.

It is unknown whether intestinal absorption of acylated anthocyanins occurs in their intact or metabolized form. In this study, with the aid of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging, intestinal absorption of acylated anthocyanins was visually investigated. Anthocyanin extracts from purple carrots were orally administered to Sprague-Dawley rats. Acylated cyanidins were absorbed into portal and circulating blood systems in their intact form, and aglycon; cyanidin 3-O-(6-O-feruloyl-ß-d-glucopyranosyl)-(1 â†’ 6)-[ß-d-xylopyranosyl-(1 â†’ 2)]-ß-d-galactopyranoside (Cy3XFGG), and showed a high absorption of 39.3 ± 0.1 pmol/mL-plasma at 60 min after administration. MALDI-MS imaging analysis of the rat jejunum membranes showed that an organic anion transporting polypeptide (OATP) transporter was involved in Cy3XFGG transport, while deacylated anthocyanins were incorporated through both the glucose transporter 2 and OATP routes. In conclusion, acylated anthocyanin, Cy3XFGG, can be absorbed in its intact form through intestinal OATP.

Evaluating the Effects of Grain of Isogenic Wheat Lines Differing in the Content of Anthocyanins in Mouse Models of Neurodegenerative Disorders.

Functional foods enriched with plant polyphenols and anthocyanins in particular attract special attention due to multiple beneficial bioactive properties of the latter. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Alzheimer's disease induced by amyloid-beta (Aß) and a transgenic mouse model of Parkinson's disease (PD) with overexpression of human alpha-synuclein. The mice were kept at a diet that consisted of the wheat grain of near isogenic lines differing in anthocyanin content for five-six months. The anthocyanin-rich diet was safe and possessed positive effects on cognitive function. Anthocyanins prevented deficits in working memory induced by Aß or a long-term grain mono-diet; they partially reversed episodic memory alterations. Both types of grain diets prolonged memory extinction and rescued its facilitation in the PD model. The dynamics of the extinction in the group fed with the anthocyanin-rich wheat was closer to that in a group of wild-type mice given standard chow. The anthocyanin-rich diet reduced alpha-synuclein accumulation and modulated microglial response in the brain of the transgenic mice including the elevated expression of arginase1 that marks M2 microglia. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition at the early stages of neurodegenerative disorders.