Anthocyanin attenuates high salt-induced hypertension via inhibiting the hyperactivity of the sympathetic nervous system.

BACKGROUND: Anthocyanin plays a protective role in cardiovascular disease through antioxidant effect. Whether anthocyanin can reduce salt-induced hypertension and the related mechanisms remain unclear. METHODS: Chronic infusion of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 µL/h) or anthocyanin (10 mg/kg, 0.4 µL/h) into bilateral paraventricular nucleus (PVN) of Sprague-Dawley rats was performed. Then, the rats were fed a high salt diet (8% NaCl, HS) or normal salt diet (0.9%, NaCl, NS) for 4 weeks. RESULTS: High salt diet induced an increase in blood pressure and peripheral sympathetic nerve activity (increased LF/HF and decreased SDNN and RMSSD), which was accompanied by increased reactive oxygen species (ROS) production and angiotensin II type-1 receptor (AT1R) expression and function in the PVN. Moreover, the NOD-like receptor protein 3 (NLRP3) and related inflammatory proteins (caspase-1) expression, the pro-inflammatory cytokine levels including IL-1ß and TNF-α were higher in PVN of rats with a high salt diet. Bilateral PVN infusion of anthocyanin attenuated NLRP3-dependent inflammation (NLRP3, caspase-1, IL-1ß and TNF-α) and ROS production, reduced AT1R expression and function in PVN and lowered peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension. CONCLUSIONS: Excessive salt intake activates NLRP3-dependent inflammation and oxidative stress and increased AT1R expression and function in the PVN. Bilateral PVN infusion of anthocyanin lowers peripheral sympathetic nerve activity and blood pressure in rats with salt-induced hypertension by improvement of expression and function of AT1R in the PVN through inhibiting NLRP3 related inflammatory and oxidative stress.

Acute Liver Failure Secondary to Anthocyanidin Use-A Case Report.

Drug-induced liver injury has become the main cause of acute liver failure (ALF). Injury may be dose-dependent or occur idiosyncratically. We report the case of a 37-year-old female patient admitted with grade 4 hepatic encephalopathy. Morosil use was initiated 30 days prior, and after 2 weeks, the case evolved with jaundice and diarrhea interspersed with constipation when the medication was discontinued. Morosil is a dry extract of the juice of red Moro oranges (Citrus species), grown in eastern Sicily (Italy). It is an important source of anthocyanidin pigments, which act as antioxidants and are used in the care and prevention of obesity, insulin resistance, hepatic steatosis, and cardiovascular diseases. According to the clinical picture and tests performed, the diagnosis of ALF was confirmed, by the criteria of Clichy and King's College. The patient was listed for liver transplantation as a priority, with the model for end stage liver disease (MELD) score: 41. Orthotopic liver transplantation was uneventfully performed using the Piggy-back technique. There are few reports in the literature of acute liver injury by other Citrus species, and we found no case reports of ALF related to the use of Morosil.

A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia.

IMPORTANCE: Identifying nutritional compounds which can reduce cognitive decline in older people is a hugely important topic. OBJECTIVE: To study the safety and effect of anthocyanins in maintaining cognitive functioning in people at increased risk for dementia. DESIGN, SETTING, AND PARTICIPANTS: Participants (206 individuals, aged 60-80 years) diagnosed with either mild cognitive impairment (MCI) or two or more cardiometabolic disorders (i.e., diabetes, hypertension, obesity) were enrolled at three different centres in Norway. INTERVENTION: Participants were randomly assigned to four capsules with a total of 320 mg/d of naturally purified anthocyanins or placebo 1:1 for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the Quality of Episodic Memory composite measure (0-100) from an online cognitive test battery CogTrack, which was administered at baseline and monthly for the next 24 weeks. Secondary outcomes included other cognitive scores from the CogTrack battery. We applied mixed effects models with a baseline test score, group, time and their interaction as fixed effects, as well as other predefined baseline covariates. The primary comparison was the group difference at week 24 based on a modified intention-to-treat principle. RESULTS: The primary analysis did not show a significant group difference at 24 weeks (78.2 versus 76.8; adjusted mean difference 1.4 (95% confidence interval -0.9-3.7); effect size 0.15; p = 0.23). However, there was a significant difference in slopes during weeks 8-24 (p = 0.007); the anthocyanin group improved while the placebo group worsened. No differences were found for the secondary cognitive outcomes. Anthocyanin capsules were well-tolerated and safe to use. CONCLUSION: Anthocyanin supplementation for 24 weeks was safe and well tolerated in people with MCI or cardiometabolic disorders. We found no significant group difference in episodic memory at the end of the study but statistically significant differences in slopes. Further studies are warranted to explore whether anthocyanins supplementation can reduce cognitive decline in people at increased risk of dementia. TRIAL REGISTRATION: ClinicalTrials.gov, (Identifier NCT03419039). http://www. CLINICALTRIALS: gov/, NCT03419039.

Insights into the Mechanisms of Action of Proanthocyanidins and Anthocyanins in the Treatment of Nicotine-Induced Non-Small Cell Lung Cancer.

In traditional medicine, different parts of plants, including fruits, have been used for their anti-inflammatory and anti-oxidative properties. Plant-based foods, such as fruits, seeds and vegetables, are used for therapeutic purposes due to the presence of flavonoid compounds. Proanthocyanidins (PCs) and anthocyanins (ACNs) are the major distributed flavonoid pigments in plants, which have therapeutic potential against certain chronic diseases. PCs and ACNs derived from plant-based foods and/or medicinal plants at different nontoxic concentrations have shown anti-non-small cell lung cancer (NSCLC) activity in vitro/in vivo models through inhibiting proliferation, invasion/migration, metastasis and angiogenesis and by activating apoptosis/autophagy-related mechanisms. However, the potential mechanisms by which these compounds exert efficacy against nicotine-induced NSCLC are not fully understood. Thus, this review aims to gain insights into the mechanisms of action and therapeutic potential of PCs and ACNs in nicotine-induced NSCLC.

Protective Effect of Bilberry Anthocyanin Extracts on Dextran Sulfate Sodium-Induced Intestinal Damage in Drosophila melanogaster.

Inflammatory bowel disease (IBD) is a chronic recurrent disease that can be controlled by various natural extracts. Anthocyanins (ANCs) from bilberry have significant antioxidant capacity and are widely used as food colors and antioxidants. In this study, we investigated the protective effects of bilberry anthocyanin extracts (BANCs) against dextran sulphate sodium (DSS)-induced intestinal inflammation in a Drosophila melanogaster (D. melanogaster) model, and the effects on the lifespan, antioxidant capacity, intestinal characteristics, and microbiome and gene expression profiles were analyzed to elucidate the underlying biological mechanisms. In DSS-induced normal and axenic D. melanogaster, BANCs significantly increased the survival rate, maintained the intestinal morphology and integrity, and reduced the number of dead intestinal epithelial cells and the ROS level of these cells. BANC supplementation had no significant effect on the intestinal microflora of DSS-induced D. melanogaster, as demonstrated by a 16S rDNA analysis, but improved the antioxidant capacity by activating the relative gene expression of NRF2 signaling pathways in the intestine of D. melanogaster with DSS-induced inflammation. Therefore, the results demonstrate that BANCs effectively alleviate intestinal inflammatory injury induced by DSS and improve the antioxidant capacity of D. melanogaster by modulating NRF2 signaling pathways, and could thus promote the application of BANCs as functional foods.

Vaccinium myrtillus L. extract associated with octocrylene, bisoctrizole, and titanium dioxide: in vitro and in vivo tests to evaluate safety and efficacy.

OBJECTIVE: The harmful effects induced by ultraviolet exposition and the significant increment in skin cancer diagnosis confirm the necessity to develop effective and safe sunscreens. Limited efficacy and cutaneous adverse reactions of traditional formulations drove the incorporation of natural extracts into multifunctional sunscreens. Vaccinium myrtillus L. extract (VME), that contains anthocyanins and flavonoids, is a potential candidate for such systems. METHODS: Considering that, we performed in vitro and in vivo tests to evaluate the sun protection factor (SPF), photostability, and safety of sunscreen samples containing VME. RESULTS: As main results, the SPF was reduced in both in vitro and in vivo evaluation in the presence of VME; nonetheless, the samples were photostable and safe. CONCLUSION: Further investigation is required to better understand the unexpected effects of VME over photoprotection, decreasing the SPF value. As a conclusion, even with interesting findings, we highlight the importance of case-by-case investigations to develop multifunctional bioactive sunscreens.

The ameliorating effects of anthocyanins on the cross-linked signaling pathways of cancer dysregulated metabolism.

Cancer cells underlie the dysregulated metabolism of carbohydrate, lipid and protein and thereby, employ interconnected cross-linked signaling pathways to supply adequate energy for growth and related biosynthetic procedures. In the present study, a comprehensive review of cancer metabolism and anthocyanin's effect was conducted using the existing electronic databases, including Medline, PubMed, Scopus, and Web of Science, as well as related articles in the field. Such keywords as "cancer", and "cancer metabolism" in the title/abstract/keyword and all the "anthocyanins" in the whole text were used. Data were collected without time restriction until February 2020. The results indicated the involvement of several signaling pathways, including inflammatory PI3K/Akt/mTOR pathway, Bax/Bcl-2/caspases as apoptosis modulators, and NF-κB/Nrf2 as oxidative stress mediators in the cancer dysregulated metabolism. Compelling studies have shown that targeting these pathways, as critical hallmarks of cancer, plays a critical role in combating cancer dysregulated metabolism. The complexity of cancer metabolism signaling pathways, along with toxicity, high costs, and resistance to conventional drugs urge the need to investigate novel multi-target agents. Increasing evidence has introduced plant-derived secondary metabolites as hopeful anticancer candidates which target multiple dysregulated cross-linked pathways of cancer metabolism. Amongst these metabolites, anthocyanins have demonstrated positive anticancer effects by targeting inflammation, oxidative stress, and apoptotic signaling pathways. The current study revealed the cross-linked signaling pathways of cancer metabolism, as well as the promising pharmacological mechanisms of anthocyanins in targeting the aforementioned signaling mediators. To overcome the pharmacokinetic limitations of anthocyanins in cancer treatment, their interactions with gut microbiota and the need to develop related nano-formulations were also considered.

Association of Strawberries and Anthocyanidin Intake with Alzheimer's Dementia Risk.

BACKGROUND: Strawberries have been identified to have antioxidant and anti-inflammatory properties that improve neuronal function and cognition, mostly in animal studies. It is unknown if the consumption of strawberries or related bioactives may reduce the risk of Alzheimer's dementia risk. MATERIAL AND METHODS: The study was conducted in 925 participants, aged 58-98 years of the Rush Memory and Aging Project. Participants were dementia-free at baseline, completed a food frequency questionnaire, and had at least two annual neurological evaluations. The diagnosis of Alzheimer's dementia was based on structured clinical neurological examination and standardized diagnostic criteria. The association of strawberry intake and incident Alzheimer's dementia was analyzed using proportional hazard models adjusted for age, sex, education, physical activity, participation in cognitive activities, APOE-ɛ4 genotype, dietary intake of other fruits, and total calorie intake. RESULTS: A total of 245 participants developed Alzheimer's dementia over the mean follow-up of 6.7 (±3.6) years. Higher strawberry intake was associated with reduced risk of Alzheimer's dementia (HR = 0.76, 95% CI: 0.60-0.96). In separate adjusted models, highest vs. lowest quartile intakes of Vitamin C (HR = 0.64, 95% CI: 0.45, 0.92), Pelargonidin (0.63, 95% CI: 0.43, 0.92), total anthocyanidins (0.69, 95% CI: 0.48, 0.99), and total flavonoids (0.67, 95% CI: 0.46, 0.98) were each associated with lower Alzheimer's dementia risk. These associations remained after further adjustment for cardiovascular conditions. CONCLUSION: Consumption of strawberries and foods rich in vitamin C, pelargonidin, anthocyanidins, and total flavonoids may reduce the risk of Alzheimer's dementia.

Natural Antioxidant Anthocyanins-A Hidden Therapeutic Candidate in Metabolic Disorders with Major Focus in Neurodegeneration.

All over the world, metabolic syndrome constitutes severe health problems. Multiple factors have been reported in the pathogenesis of metabolic syndrome. Metabolic disorders result in reactive oxygen species (ROS) induced oxidative stress, playing a vital role in the development and pathogenesis of major health issues, including neurological disorders Alzheimer's disease (AD) Parkinson's disease (PD). Considerable increasing evidence indicates the substantial contribution of ROS-induced oxidative stress in neurodegenerative diseases. An imbalanced metabolism results in a defective antioxidant defense system, free radicals causing inflammation, cellular apoptosis, and tissue damage. Due to the annual increase in financial and social burdens, in addition to the adverse effects associated with available synthetic agents, treatment diversion from synthetic to natural approaches has occurred. Antioxidants are now being considered as convincing therapeutic agents against various neurodegenerative disorders. Therefore, medicinal herbs and fruits currently receive substantially more attention as commercial sources of antioxidants. In this review, we argue that ROS-targeted therapeutic interventions with naturally occurring antioxidant flavonoid, anthocyanin, and anthocyanin-loaded nanoparticles might be the ultimate treatment against devastating illnesses. Furthermore, we elucidate the hidden potential of the neuroprotective role of anthocyanins and anthocyanin-loaded nanoparticles in AD and PD neuropathies, which lack sufficient attention compared with other polyphenols, despite their strong antioxidant potential. Moreover, we address the need for future research studies of native anthocyanins and nano-based-anthocyanins, which will be helpful in developing anthocyanin treatments as therapeutic mitochondrial antioxidant drug-like regimens to delay or prevent the progression of neurodegenerative diseases, such as AD and PD.

Intake of Anthocyanins and Gastric Cancer Risk: A Comprehensive Meta-Analysis on Cohort and Case-Control Studies.

This meta-analysis aimed to explore the association between anthocyanins intake and the risk of gastric cancer. All the relative articles have been searched in the online databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library until June 11th, 2018. Risk ratios (RRs) or odds ratio (ORs) and their 95% confidence intervals were calculated and pooled through the STATA 12.0. A total of 6 studies were finally selected in the meta-analysis. No significant association was found between total anthocyanins consumption and gastric cancer risk (RR=0.92, 95%CI: 0.81-1.04). Likewise, there was also no significant evidence of the relationship between anthocyanins intake and gastric cancer in tumor site (cardia: RR=0.90, 95%CI: 0.62-1.31; noncardia: RR=0.86, 95%CI: 0.69-1.07) and gender (men: RR=1.02, 95%CI: 0.73-1.40; women: RR=0.80, 95%CI: 0.52-1.23). The dose-response relationship was also not found in this meta-analysis. The Grades of Recommendations Assessment, Development and Evaluation (GRADE) quality in our study was very low. The results of our meta-analysis suggested the intake of anthocyanins had no association with the risk of gastric cancer and further studies are needed.

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses.

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.

Role of Purified Anthocyanins in Improving Cardiometabolic Risk Factors in Chinese Men and Women with Prediabetes or Early Untreated Diabetes-A Randomized Controlled Trial.

Objective: In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia. Research Design and Methods: This was a 12-week randomized, double-blind, placebo-controlled trial. A total of 160 participants aged 40-75 years with prediabetes or early untreated diabetes were randomly allocated to receive either purified anthocyanins (320 mg/day, n = 80) or placebo (n = 80) of identical appearance. A three-hour oral glucose tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and lipids) were measured at baseline and at the end of the trial. Results: A total of 138 subjects completed the protocol. Compared with placebo, purified anthocyanins moderately reduced HbA1c (-0.14%, 95% CI: -0.23~-0.04%; p = 0.005), low-density lipoprotein-c (LDL-c) (-0.2 mmol/L, 95% CI: -0.38~-0.01, p = 0.04), apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17; p = 0.02), and apolipoprotein B (apo B) (-0.07 g/L, 95% CI: -0.13~-0.01; p = 0.01) according to intention-to-treat analysis. Subgroup analyses suggested that purified anthocyanins were more effective at improving glycemic control, insulin sensitivity, and lipids among patients with elevated metabolic markers. Conclusions: The 12-week randomized controlled trials (RCT) in Chinese adults with prediabetes or early untreated diabetes indicated that purified anthocyanins favorably affected glycemic control and lipid profile. Future studies of a longer duration that explore the dose-response relationship among patients with cardiometabolic disorders are needed to confirm our findings.

Dietary Anthocyanins and Insulin Resistance: When Food Becomes a Medicine.

Insulin resistance is an abnormal physiological state that occurs when insulin from pancreatic ß-cells is unable to trigger a signal transduction pathway in target organs such as the liver, muscles and adipose tissues. The loss of insulin sensitivity is generally associated with persistent hyperglycemia (diabetes), hyperinsulinemia, fatty acids and/or lipid dysregulation which are often prevalent under obesity conditions. Hence, insulin sensitizers are one class of drugs currently employed to treat diabetes and associated metabolic disorders. A number of natural products that act through multiple mechanisms have also been identified to enhance insulin sensitivity in target organs. One group of such compounds that gained interest in recent years are the dietary anthocyanins. Data from their in vitro, in vivo and clinical studies are scrutinized in this communication to show their potential health benefit through ameliorating insulin resistance. Specific mechanism of action ranging from targeting specific signal transduction receptors/enzymes to the general antioxidant and anti-inflammatory mechanisms of insulin resistance are presented.

Bilberry extracts are not created equal: the role of non anthocyanin fraction. Discovering the "dark side of the force" in a preliminary study.

OBJECTIVE: Several experimental studies and clinical trials support the potential of bilberry (Vaccinium myrtillus L) extracts in promoting eye health and circulation. Many active ingredients have been isolated from the berries and leaves of the bilberry plant. However, anthocyanins represent the most widely studied bioactive compounds in this plant. PATIENTS AND METHODS: The aim of this registry, supplement study was to evaluate the effects of Mirtoselect® (standardized in 36% anthocyanins and obtained by an industrial extraction process that preserves the full range of the non-anthocyanin components, mainly natural sugars and polyphenols) in different types of retinal vasculopathies. In total, 140 patients with different types of retinopathy spontaneously decided to join one of the following groups: standard management (SM) only (n=38); SM associated with Mirtoselect® supplementation (n=47); SM associated with a generic bilberry extract supplementation (n=55). Retinal circulatory parameters and flow measurements of the retinal vessels were evaluated at the inclusion and after 6-months supplementation. RESULTS: Overall, significant improvements in several retinal circulatory parameters such as retinal blood flow velocity, with respect to the values at inclusion, were observed in both supplementation groups, especially in Mirtoselect® supplementation group. However, at 6 months, inter-group comparison revealed a statistical advantage in all tested parameters for Mirtoselect® supplementation groups. No side effects or tolerability concerns were reported. CONCLUSIONS: Our registry study suggests that Mirtoselect® supplementation could represent an effective and safe integrated approach for the treatment of different retinopathies.

Preparation and toxicological evaluation of methyl pyranoanthocyanin.

Anthocyanins are increasingly valued in the food industry for their functional properties and as food colorants. The broadness of their applications has, however, been limited by the lack of stability of these natural pigment extracts in a number of food systems. The potential application of pyranoanthocyanins, anthocyanin derivatives with better stability conferred by the added pyran ring, as a food ingredient was determined. Methylpyranoanthocyanin (MPA) was prepared from reaction of acetone and anthocyanin extracts from red grapes. Reaction products were sequentially purified with polyamide resin, TSK gel resin and semi-preparative HPLC to a purity level >98%. Cytoprotective influence tests of the purified MPA indicated its significant protective effect against H2O2 induced MRC-5 cell damage. Results of evaluations of possible acute toxicity effects on MPA-fed mice, including macro and microscopic assessments, support the conclusion of a non-toxic effect of MPA, and its potential safe use as a food additive.

Toxicological studies of stem bark extract from Schefflera barteri Harms (Araliaceae).

BACKGROUND: The use of herbal medicines as complements or alternatives to orthodox medicines has been on the increase. There has been the erroneous belief that these medicines are free from adverse effects. Schefflera barteri is popularly used in the West region of Cameroon for the treatment of various diseases such as diarrhea, spasm, pneumonia and animals bite. Considering the ethnopharmacological relevance of this plant, this study was designed to investigate the possible toxic effects of the stem bark extract of S. barteri. METHODS: The extract was prepared by maceration of stem bark dry powder in methylene chloride/methanol mixture. Phytochemical analysis was performed by chemical reaction method. Oral acute toxicity study was carried out by administering single geometric increasing doses (2 to 16 g/kg body weight) of plant extract to Swiss albino mice. For sub-acute toxicity study, repeated doses (100, 200, 400 and 800 mg/kg bw) of plant extract were given to Wistar albino rats for 28 consecutive days by oral route. At the end of the treatment period, hematological and biochemical parameters were assessed, as well as histopathological studies. RESULTS: Phytochemical analysis of stem bark extract of S. barteri revealed the presence of anthocyanins, anthraquinons and saponins. Acute toxicity results showed that the LD50 was greater than 16000 mg/kg. Sub-acute treatment significantly (P < 0.05) increased the level of serum transaminase, proteins and HDL cholesterol. On the other hand, the extract significantly (P < 0.05) reduced the level of leucocytes as well as neutrophils, basophils and monocytes in female. No significant variation of serum creatinine, LDL cholesterol, serum triglycerides as well as liver, spleen, testicles and ovaries proteins was noted. Histopathological analysis of organs showed vascular congestion, inflammation of peri-portal and vacuolization of hepatocytes at the level of the liver. Leucocytes infiltration of peri-portal veins were noticed on lungs and liver cells as well as inflammatory peri-bronchial and basal membranes seminar tube merely joined on lungs and testis respectively. CONCLUSION: The results suggest that acute administration of the stem bark extract of S. barteri is associated with signs of toxicity, administration over a long duration provokes hepatotoxicity, testes and lungs toxicities.

Dietary anthocyanins as a complementary medicinal approach for management of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is thought to result from a chronic or relapsing activation of the immune system in the GI tract. A growing body of evidence confirms the health benefits of dietary anthocyanins as plant-derived natural agents. The aim of this review is to provide an overview of several natural products rich in anthocyanins used worldwide for the treatment of IBD. Anthocyanins possess both protective and therapeutic functions in the management of IBD by alleviating oxidative stress processes, cytoprotective functions, downregulation of inflammatory cytokines and suppressing cellular signaling pathways of inflammatory processes. In conclusion, the consumption of anthocyanin-rich natural formulations must be promoted on the basis of their possible function in the prevention and treatment of gastrointestinal inflammatory disorders.

The protective effects of berry-derived anthocyanins against visible light-induced damage in human retinal pigment epithelial cells.

BACKGROUND: Studies have shown that anthocyanins (ACNs) in berries contribute to eye health. However, information on the relationship between the chemical structures and visual functions of ACNs is scarce. This study investigated the protection effects of ACNs with different structures against visible light-induced damage in human retinal pigment epithelial (RPE) cells. RESULTS: Four ACNs with different aglycones, namely, pelargonidin-3-glucoside (Pg-3-glu), cyanidin-3-glucoside (Cy-3-glu), delphinidin-3-glucoside, and malvidin-3-glucoside (Mv-3-glu), were isolated from three berries (blueberry, blackberry and strawberry). Of these ACNs, Cy-3-glu exhibited the highest reactive oxygen species inhibitory capacity in RPE cells, with 40 µg mL(-1) Cy-3-glu showing a ROS clearance of 57.5% ± 4.2%. The expression of vascular endothelial growth factor levels were significantly (P < 0.05) down-regulated by Cy-3-glu and Mv-3-glu in a visible light-induced damage RPE cell model. Cy-3-glu and Pg-3-glu treatments significantly (P < 0.05) inhibited the increase in ß-galactosidase during the RPE cell ageing caused by visible light exposure. CONCLUSION: Our findings suggest that the biological properties of different ACNs significantly vary. Cy-3-glu, which contains an ortho hydroxyl group in its B ring, possibly exerts multiple protective effects (antioxidant, anti-angiogenic and anti-ageing) in RPE cells. Therefore, Cy-3-glu may prove useful as a prophylactic health food for the prevention of retinal diseases.

Anthocyanin-rich açaí (Euterpe oleracea Mart.) extract attenuates manganese-induced oxidative stress in rat primary astrocyte cultures.

Manganese (Mn) is an essential element for human health. However, at high concentrations Mn may be neurotoxic. Mn accumulates in astrocytes, affecting their redox status. In view of the high antioxidant and anti-inflammatory properties of the exotic Brazilian fruit açaí (Euterpe oleracea Mart.), its methanolic extract was obtained by solid-phase extraction (SPE). This açaí extract showed considerable anthocyanins content and direct antioxidant capacity. The açaí extract scavenged 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) with an EC50 of 19.1 ppm, showing higher antioxidant activity compared to butylated hydroxytoluene (BHT), but lower than ascorbic acid and quercetin. This obtained açaí extract also attenuated Mn-induced oxidative stress in primary cultured astrocytes. Specifically, the açaí extract at an optimal and nutritionally relevant concentration of 0.1 µg/ml prevented Mn-induced oxidative stress by (1) restoring GSH/GSSG ratio and net glutamate uptake, (2) protecting astrocytic membranes from lipid peroxidation, and (3) decreasing Mn-induced expression of erythroid 2-related factor (Nrf2) protein. A larger quantity of açaí extract exacerbated the effects of Mn on these parameters except with respect to lipid peroxidation assessed by means of F2-isoprostanes. These studies indicate that at nutritionally relevant concentration, anthocyanins obtained from açaí protect astrocytes against Mn neurotoxicity, but at high concentrations, the "pro-oxidant" effects of its constituents likely prevail. Future studies may be profitably directed at potential protective effects of açaí anthocyanins in nutraceutical formulations.

Peironimev-Plus® in the treatment of chronic inflammation of tunica albuginea (Peyronie's disease). results of a controlled study.

Peyronie's Disease (PD) is a connective tissue disorder involving the growth of fibrous plaques in penile corpora cavernosa (tunica albuginea). The conservative treatment is indicated in the development stage of PD for at least one year after diagnosis and in case of penile pain. This study was conducted to demonstrate the possible effectiveness of the new substances of Peironimev-plus®. Sixty four patients (age: 29-65 years, mean: 52.57 ± 9.06) diagnosed with PD were enrolled in a medical treatment. All patients underwent the following diagnostic tests: penile ultrasound, photographic documentation of penile curvature, IIEF questionnaire (erectile function score), pain evaluation with Visual Analogue pain Scale (VAS). The patients were divided into two treatment groups with different combinations of drugs: A = Peironimev-plus/oral/one tablet-daily + Verapamil injection (peri-lesional) 10 mg/every two weeks + Verapamil iontophoresis/5 mg/three times a week - for 6 months; B = Verapamil injection (peri-lesional) 10 mg/every two weeks + Verapamil iontophoresis/5 mg/three times a week - for 6 months. Intergroup analysis revealed statistically significant differences: in group A the effective plaque size reduction was -30.8% while in the group B the reduction was -18.0% (p=0.000). In group A the improvement of curvature occurred in 85.1% of the cases while in group B this occurred only in 53.5% (p=0.024), moreover the mean curvature decrease was respectively - 8.7° and - 4.6° (p=0.002). IIEF score was significantly improved in group A patients with erectile dysfunction (p=0.02). Our results suggest that Peironimev-plus is an effective drug in treating PD and it may help to prevent the progression of PD.