Black Rice Anthocyanins as An Effective Antioxidant of Inhibition of Oil Oxidative Based on Molecular Modification.

This present work investigated the influence of black rice anthocyanins as antioxidants on the oxidation stability of oil. Malonic acid, succinic acid and succinic anhydride were grafted on black rice anthocyanins through acylation method to improve their antioxidant activity in oil. The results from fourier transform infrared spectroscopy (FTIR) showed new absorption peaks near 1744 cm -1 and 1514 cm -1 , which implied that malonic acid, succinic acid and succinic anhydride grafted on the -OH of glucoside and rutinoside through esterification reaction and resulted that the polarity of these were reduced. Total content of anthocyanin (TAC) decreased to 166. 3 mg/g, 163.7 mg/g and 150.2 mg/g, respectively after modification with succinic acid, malonic acid and succinic anhydride. Compared with native anthocyanins, the acylation of black rice anthocyanins partially reduced its antioxidant activity. In addition, DPPH clearance of molecular modified anthocyanins decreased to 62.6% (San-An). As revealed in the oil stability through the determination of primary oxidation products (PV) and secondary oxidation products (p-AV), Sa-An, Ma-An and San-An showed stronger antioxidant activity in Schaal oven accelerated oxidation test during 12 days than native black rice anthocyanin in both corn oil and flaxseed oil. Molecular modified black rice anthocyanins are expected to be used as colorants, antioxidants, etc. in oil-rich food.

Polyphenol nanoparticles based on bioresponse for the delivery of anthocyanins.

Anthocyanin (AN) has good antioxidant and anti-inflammatory bioactivities, but its poor biocompatibility and low stability limit the application of AN in the food industry. In this study, core-shell structured carriers were constructed by noncovalent interaction using tannic acid (TA) and poloxamer 188 (F68) to improve the biocompatibility, stability and smart response of AN. Under different treatment conditions, TA-F68 and AN were mainly bound by hydrophobic interaction. The PDI is less than 0.1, and the particle size of nanoparticles (NPs) is uniform and concentrated. The retention of the complex was 15.50 % higher than that of AN alone after 9 d of light treatment. After heat treatment for 180 min, the retention rate after loading was 13.87 % higher than that of AN alone. The carrier reduce the damage of AN by the digestive environment, and intelligently and sustainedly release AN when the esterase is highly expressed. In vitro studies demonstrated that the nanocarriers had good biocompatibility and significantly inhibited the overproduction of reactive oxygen species induced by oxidative stress. In addition, AN-TA-F68 has great potential for free radical scavenging at sites of inflammation. In conclusion, the constructed nano-delivery system provides a potential application for oral ingestion of bioactive substances for intervention in ulcerative colitis.

Anti-Atherosclerotic Properties of Aronia melanocarpa Extracts Influenced by Their Chemical Composition Associated with the Ripening Stage of the Berries.

The high content of bioactive compounds in Aronia melanocarpa fruit offers health benefits. In this study, the anti-atherosclerotic effect of Aronia extracts was assessed. The impact on the level of adhesion molecules and the inflammatory response of human umbilical vein endothelial cells (HUVECs) was shown in relation to the chemical composition and the stage of ripening of the fruits. Samples were collected between May (green, unripe) and October (red, overripe) on two farms in Poland, which differed in climate. The content of chlorogenic acids, anthocyanins, and carbohydrates in the extracts was determined using HPLC-DAD/RI. The surface expression of ICAM-1 and VCAM-1 in HUVECs was determined by flow cytometry. The mRNA levels of VCAM-1, ICAM-1, IL-6, and MCP-1 were assessed using the quantitative real-time PCR method. The farms' geographical location was associated with the quantity of active compounds in berries and their anti-atherosclerotic properties. Confirmed activity for green fruits was linked to their high chlorogenic acid content.

Wild Blueberry Extract Intervention in Healthy Older Adults: A Multi-Study, Randomised, Controlled Investigation of Acute Cognitive and Cardiovascular Effects.

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

Effects of Red Sorghum-Derived Deoxyanthocyanidins and Their O-ß-D-Glucosides on E-Cadherin Promoter Activity in PC-3 Prostate Cancer Cells.

Although much less common than anthocyanins, 3-Deoxyanthocyanidins (3-DAs) and their glucosides can be found in cereals such as red sorghum. It is speculated that their bioavailability is higher than that of anthocyanins. Thus far, little is known regarding the therapeutic effects of 3-DAs and their O-ß-D-glucosides on cancer, including prostate cancer. Thus, we evaluated their potential to decrease cell viability, to modulate the activity of transcription factors such as NFκB, CREB, and SOX, and to regulate the expression of the gene CDH1, encoding E-Cadherin. We found that 4',7-dihydroxyflavylium chloride (P7) and the natural apigeninidin can reduce cell viability, whereas 4',7-dihydroxyflavylium chloride (P7) and 4'-hydroxy-7-O-ß-D-glucopyranosyloxyflavylium chloride (P3) increase the activities of NFkB, CREB, and SOX transcription factors, leading to the upregulation of CDH1 promoter activity in PC-3 prostate cancer cells. Thus, these compounds may contribute to the inhibition of the epithelial-to-mesenchymal transition in cancer cells and prevent the metastatic activity of more aggressive forms of androgen-resistant prostate cancer.

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.

Effects of Anthocyanins on Components of Metabolic Syndrome-A Review.

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

A grape-supplemented diet prevented ultraviolet (UV) radiation-induced cataract by regulating Nrf2 and XIAP pathways.

The purpose of this study is to investigate if grape consumption, in the form of grape powder (GP), could protect against ultraviolet (UV)-induced cataract. Mice were fed with the regular diet, sugar placebo diet, or a grape diet (regular diet supplemented with 5%, 10%, and 15% GP) for 3 months. The mice were then exposed to UV radiation to induce cataract. The results showed that the GP diet dose-dependently inhibited UV-induced cataract and preserved glutathione pools. Interestingly, UV-induced Nrf2 activation was abolished in the groups on the GP diet, suggesting GP consumption may improve redox homeostasis in the lens, making Nrf2 activation unnecessary. For molecular target prediction, a total of 471 proteins regulated by GP were identified using Agilent Literature Search (ALS) software. Among these targets, the X-linked inhibitor of apoptosis (XIAP) was correlated with all of the main active ingredients of GP, including resveratrol, catechin, quercetin, and anthocyanins. Our data confirmed that GP prevented UV-induced suppression of XIAP, indicating that XIAP might be one of the critical molecular targets of GP. In conclusion, this study demonstrated that GP protected the lens from UV-induced cataract development in mice. The protective effects of GP may be attributed to its ability to improve redox homeostasis and activate the XIAP-mediated antiapoptotic pathway.

Modulation of Gut Microbial Metabolism by Cyanidin-3-O-Glucoside in Mitigating Polystyrene-Induced Colonic Inflammation: Insights from 16S rRNA Sequencing and Metabolomics.

Microplastics derived from plastic waste have emerged as a pervasive environmental pollutant with potential transfer and accumulation through the food chain, thus posing risks to both ecosystems and human health. The gut microbiota, tightly intertwined with metabolic processes, exert substantial influences on host physiology by utilizing dietary compounds and generating bacterial metabolites such as tryptophan and bile acid. Our previous studies have demonstrated that exposure to microplastic polystyrene (PS) disrupts the gut microbiota and induces colonic inflammation. Meanwhile, intervention with cyanidin-3-O-glucoside (C3G), a natural anthocyanin derived from red bayberry, could mitigate colonic inflammation by reshaping the gut bacterial composition. Despite these findings, the specific influence of gut bacteria and their metabolites on alleviating colonic inflammation through C3G intervention remains incompletely elucidated. Therefore, employing a C57BL/6 mouse model, this study aims to investigate the mechanisms underlying how C3G modulates gut bacteria and their metabolites to alleviate colonic inflammation. Notably, our findings demonstrated the efficacy of C3G in reversing the elevated levels of pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and the upregulation of mRNA expression (Il-6, Il-1ß, and Tnf-α) induced by PS exposure. Meanwhile, C3G effectively inhibited the reduction in levels (IL-22, IL-10, and IL-4) and the downregulation of mRNA expression (Il-22, Il-10, and Il-4) of anti-inflammatory cytokines induced by PS exposure. Moreover, PS-induced phosphorylation of the transcription factor NF-κB in the nucleus, as well as the increased level of protein expression of iNOS and COX-2 in the colon, were inhibited by C3G. Metabolisms of gut bacterial tryptophan and bile acids have been extensively implicated in the regulation of inflammatory processes. The 16S rRNA high-throughput sequencing disclosed that PS treatment significantly increased the abundance of pro-inflammatory bacteria (Desulfovibrio, norank_f_Oscillospiraceae, Helicobacter, and Lachnoclostridium) while decreasing the abundance of anti-inflammatory bacteria (Dubosiella, Akkermansia, and Alistipes). Intriguingly, C3G intervention reversed these pro-inflammatory changes in bacterial abundances and augmented the enrichment of bacterial genes involved in tryptophan and bile acid metabolism pathways. Furthermore, untargeted metabolomic analysis revealed the notable upregulation of metabolites associated with tryptophan metabolism (shikimate, l-tryptophan, indole-3-lactic acid, and N-acetylserotonin) and bile acid metabolism (3b-hydroxy-5-cholenoic acid, chenodeoxycholate, taurine, and lithocholic acid) following C3G administration. Collectively, these findings shed new light on the protective effects of dietary C3G against PS exposure and underscore the involvement of specific gut bacterial metabolites in the amelioration of colonic inflammation.

Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., ß-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.

Rubus Occidentalis and its bioactive compounds against cancer: From molecular mechanisms to translational advances.

BACKGROUND: Cancer ranks as the second leading cause of death globally, imposing a significant public health burden. The rise in cancer resistance to current therapeutic agents underscores the potential role of phytotherapy. Black raspberry (BRB, Rubus Occidentalis) is a fruit rich in anthocyanins, ellagic acid, and ellagitannins. Accumulating evidence suggests that BRB exhibits promising anticancer effects, positioning it as a viable candidate for phytotherapy. PURPOSE: This article aims to review the existing research on BRB regarding its role in cancer prevention and treatment. It further analyzes the effective components of BRB, their metabolic pathways, and the potential mechanisms underlying the fruit's anticancer effects. METHODS: Ovid MEDLINE, EMBASE, Web of Science, and CENTRAL were searched through the terms of Black Raspberry, Raspberry, and Rubus Occidentali up to January 2023. Two reviewers performed the study selection by screening the title and abstract. Full texts of potentially eligible studies were retrieved to access the details. RESULTS: Out of the 767 articles assessed, 73 papers met the inclusion criteria. Among them, 63 papers investigated the anticancer mechanisms, while 10 conducted clinical trials focusing on cancer treatment or prevention. BRB was found to influence multiple cancer hallmarks by targeting various pathways. Decomposition of free radicals and regulation of estrogen metabolism, BRB can reduce DNA damage caused by reactive oxygen species. BRB can also enhance the function of nucleotide excision repair to repair DNA lesions. Through regulation of epigenetics, BRB can enhance the expression of tumor suppressor genes, inducing cell cycle arrest, and promoting apoptosis and pyroptosis. BRB can reduce the energy and nutrients supply to the cancer nest by inhibiting glycolysis and reducing angiogenesis. The immune and inflammatory microenvironment surrounding cancer cells can also be ameliorated by BRB, inhibiting cancer initiation and progression. However, the limited bioavailability of BRB diminishes its anticancer efficacy. Notably, topical applications of BRB, such as gels and suppositories, have demonstrated significant clinical benefits. CONCLUSION: BRB inhibits cancer initiation, progression, and metastasis through diverse anticancer mechanisms while exhibiting minimal side effects. Given its potential, BRB emerges as a promising phototherapeutic agent for cancer treatment.

Anthocyanins: Potential phytochemical candidates for the amelioration of non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is described by too much hepatic fat deposition causing steatosis, which further develops into nonalcoholic steatohepatitis (NASH), defined by necroinflammation and fibrosis, progressing further to hepatic cirrhosis, hepatocellular carcinoma, and liver failure. NAFLD is linked to different aspects of the metabolic syndrome like obesity, insulin resistance, hypertension, and dyslipidemia, and its pathogenesis involves several elements including diet, obesity, disruption of lipid homeostasis, and a high buildup of triglycerides and other lipids in liver cells. It is therefore linked to an increase in the susceptibility to developing diabetes mellitus and cardiovascular diseases. Several interventions exist regarding its management, but the availability of natural sources through diet will be a benefit in dealing with the disorder due to the immensely growing dependence of the population worldwide on natural sources owing to their ability to treat the root cause of the disease. Anthocyanins (ACNs) are naturally occurring polyphenolic pigments that exist in the form of glycosides, which are the glucosides of anthocyanidins and are produced from flavonoids via the phenyl propanoid pathway. To understand their mode of action in NAFLD and their therapeutic potential, the literature on in vitro, in vivo, and clinical trials on naturally occurring ACN-rich sources was exhaustively reviewed. It was concluded that ACNs show their potential in the treatment of NAFLD through their antioxidant properties and their efficacy to control lipid metabolism, glucose homeostasis, transcription factors, and inflammation. This led to the conclusion that ACNs possess efficacy in the amelioration of NAFLD and the various features associated with it. However, additional clinical trials are required to justify the potential of ACNs in NAFLD.

Intelligent carboxymethyl cellulose composite films containing Garcinia mangostana shell anthocyanin with improved antioxidant and antibacterial properties.

In this study, anthocyanin from Garcinia mangostana shell extract (Mse) was used as pH indicator to prepare intelligent carboxymethyl cellulose (CMC) based composite films. The structure and properties of the CMC-based composite films were characterized and discussed in detail. Results showed that the CMC-based composite films with Mse had excellent mechanical, antibacterial and antioxidant abilities. Especially, the carboxymethyl cellulose/corn starch/Garcinia mangostana shell extract (CMC/Cst/Mse) composite film had best mechanical properties (20.62 MPa, 4.06 % EB), lowest water vapor permeability (1.80 × 10-12 g·cm/(cm2·s·Pa)), excellent ultraviolet (UV) blocking performance, and the best antibacterial and antioxidant abilities. The pH sensitivity of composite films which had Mse obviously changed with time when the fish freshness was monitored at 25 °C. Given the good pH sensitivity of the composite films, it had significant potential for application of intelligent packaging film as a food packaging material to indicate the freshness of fish.

Pomegranate extract-loaded sphingosomes for the treatment of cancer: Phytochemical investigations, formulation, and antitumor activity evaluation.

AIM: Formulation of Pomegranate Extracts (PE)-loaded sphingosomes as an antitumor therapy for the intravenous and passive targeted delivery to various tumor types, especially that of the breast, colon, and uterus; to increase the therapeutic activity and decrease the adverse effects profile. METHODS: The pericarp and seeds' juice of Punica granatum were each extracted using D.W. and ethanol. Phytochemical investigation of all extracts was carried out including total phenolics, flavonoids, and anthocyanins contents, the antioxidant activity, as well as HPLC analysis of phenolics and flavonoids. The antitumor potential of all extracts was also tested utilizing three cell lines: MCF-7, HeLa, and HCT116. The candidate extract was chosen for the formulation phase and was entrapped into the sphingosomes using the thin-film hydration method and employing three different PE: lipids weight ratios. The synthesized formulations were characterized for their size, morphological features, zeta potential, entrapment efficiency, and in vitro drug release and kinetics modeling studies. The optimized formula was further analyzed by FTIR spectroscopy and electron microscopy. The antitumor activity of F2 was also investigated using the same cancer cell lines compared to the plant extract. RESULTS: The highest phenolics, flavonoids, and anthocyanins contents were observed in the ethanolic pericarps extract (EPE), followed by the ethanolic seeds extract (ESE). Consequently, EPE showed a higher antitumor activity hence it was selected for the formulation phase. PE-loaded sphingosomes formula (F2) was selected for having the highest EE% (71.64%), and a sustained release profile with the highest in vitro release (42.5±9.44%). By employing the DDSolver, the Weibull model was found the most suitable to describe the PE release kinetics compared to other models. The release mechanism was found to follow Fickian diffusion. Simulated pharmacokinetic parameters have portrayed F2 as the candidate formula, with the highest AUC (536.095) and slowest MDT (0.642 h). In addition, F2 exhibited a significant (p>0.05) stronger and prolonged anticancer effect against MCF-7, HeLa, and HCT116 cell lines at all concentrations tested compared to the free extract. CONCLUSION: The results proved that sphingosomes are an effective delivery system, improving pharmacological efficacy and reducing serious side effects of anticancer medications and natural products.

Health-Promoting Properties of Anthocyanins from Cornelian Cherry (Cornus mas L.) Fruits.

The cornelian cherry is a plant that annually provides fruits, drupe-type, ranging in color from yellow through pink, red, carmine, and almost black. Cornelian cherry bears abundant fruit in temperate climate conditions, which means that its dark-colored fruits can be treated as an excellent source of anthocyanins. After consuming, anthocyanins have a protective function in the human body. Raw fruit extracts and their pure isolates, rich in anthocyanins, have a wide spectrum of health-promoting properties. This review focuses on the health-promoting properties of anthocyanins from fruits of cornelian cherry, documented in research conducted in vitro, in vivo, and in humans. The results obtained so far confirm the beneficial effects of anthocyanins on the blood parameters, whose values are important in predicting and assessing the risk and progression of cardiovascular and metabolic diseases. A beneficial effect on molecular and histopathological changes in target organs such as the heart, brain, kidneys, and liver has also been demonstrated. Anthocyanins from cornelian cherry have a strong antioxidant effect, which explains their protective effects on organs and anticancer effects. Moreover, they have antiglycemic, antihyperlipidemic, anti-inflammatory, and antimicrobial properties. The work highlights the perspectives and directions of necessary research.

The INHABIT (synergIstic effect of aNtHocyAnin and proBIoTics in) Inflammatory Bowel Disease trial: a study protocol for a double-blind, randomised, controlled, multi-arm trial.

Ulcerative Colitis (UC), a type of Inflammatory Bowel Disease (IBD), is a chronic, relapsing gastrointestinal condition with increasing global prevalence. The gut microbiome profile of people living with UC differs from healthy controls and this may play a role in the pathogenesis and clinical management of UC. Probiotics have been shown to induce remission in UC; however, their impact on the gut microbiome and inflammation is less clear. Anthocyanins, a flavonoid subclass, have shown anti-inflammatory and microbiota-modulating properties; however, this evidence is largely preclinical. To explore the combined effect and clinical significance of anthocyanins and a multi-strain probiotic, a 3-month randomised controlled trial will be conducted in 100 adults with UC. Participants will be randomly assigned to one of four groups: anthocyanins (blackcurrant powder) + placebo probiotic, probiotic + placebo fruit powder, anthocyanin + probiotic, or double placebo. The primary outcome is a clinically significant change in the health-related quality-of-life measured with the Inflammatory Bowel Disease Questionnaire-32. Secondary outcomes include shotgun metagenomic sequencing of the faecal microbiota, faecal calprotectin, symptom severity, and mood and cognitive tests. This research will identify the role of adjuvant anti-inflammatory dietary treatments in adults with UC and elucidate the relationship between the gut microbiome and inflammatory biomarkers in this disease, to help identify targeted individualised microbial therapies. ANZCTR registration ACTRN12623000630617.

Malvidin promotes PGC-1α/Nrf2 signaling to attenuate the inflammatory response and restore mitochondrial activity in septic acute kidney injury.

Acute kidney injury (AKI) in sepsis is a vital and dangerous organ failure caused by an infection-induced dysregulation of the host reaction. Malvidin possesses significant anti-inflammatory and antioxidant bioactivities. This study explored the critical roles of malvidin in sepsis AKI and the crosstalk among mitochondrial function, nucleotide-binding oligomerization-like receptor 3 (NLRP3) inflammasome and nuclear factor erythroid 2 (Nrf2) signaling pathway. First, C57BL/6 mice were administered lipopolysaccharide intraperitoneally for 6 h to create an AKI model of sepsis. Hematoxylin-eosin staining and serum biomarker assays showed that malvidin protected from AKI in sepsis. Real-time fluorescence quantitative polymerase chain reaction analysis revealed that malvidin was able to inhibit inflammatory cytokines and mediators. Western blot assays indicated that malvidin suppressed NLRP3 inflammasome activation and enhanced antioxidant properties. Additionally, human renal tubular epithelial cells were stimulated by lipopolysaccharide/adenosine triphosphate to establish an NLRP3 inflammasome activation model in vitro, and in line with findings in vivo, malvidin significantly inhibited NLRP3 inflammasome activation. Furthermore, our data indicate that malvidin restored mitochondrial quality and function, reduced reactive oxygen species production, increased mitochondrial membrane potential, enhanced mitochondrial DNA copy number, and promoted peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) nuclear translocation. Moreover, inhibitor blockade assays indicated that both PGC-1α and Nrf2 affected the inhibition of the NLRP3 inflammasome by malvidin. Finally, immunoprecipitation assays showed that malvidin promoted PGC-1α and Nrf2 interactions. Overall, malvidin alleviated lipopolysaccharide-induced sepsis AKI, improved mitochondrial function and mitochondrial biogenesis, and inhibited the NLRP3 inflammasome through the PGC-1α/Nrf2 signaling pathway, suggesting that malvidin might translate into clinical applications for sepsis AKI therapy.

In Vitro Inhibitory Potential of Different Anthocyanin-Rich Berry Extracts in Murine CT26 Colon Cancer Cells.

Anti-oxidant, -inflammatory, and -carcinogenic activities of bioactive plant constituents, such as anthocyanins, have been widely discussed in literature. However, the potential interaction of anthocyanin-rich extracts with routinely used chemotherapeutics is still not fully elucidated. In the present study, anthocyanin-rich polyphenol extracts of blackberry (BB), bilberry (Bil), black currant (BC), elderberry (EB), and their respective main anthocyanins (cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, cyanidin-3-O-rutinoside, and cyanidin-3-O-sambubioside) were investigated concerning their cytotoxic and DNA-damaging properties in murine CT26 cells either alone or in combination with the chemotherapeutic agent SN-38. BB exerted potent cytotoxic effects, while Bil, BC, and EB only had marginal effects on cell viability. Single anthocyanins comprised of the extracts could not induce comparable effects. Even though the BB extract further pronounced SN-38-induced cytotoxicity and inhibited cell adhesion at 100-200 µg/mL, no effect on DNA damage was observed. In conclusion, anti-carcinogenic properties of the extracts on CT26 cells could be ranked BB >> BC ≥ Bil ≈ EB. Mechanisms underlying the potent cytotoxic effects are still to be elucidated since the induction of DNA damage does not play a role.

The Role of Cyanidin-3-O-glucoside in Modulating Oxaliplatin Resistance by Reversing Mesenchymal Phenotype in Colorectal Cancer.

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

Src Tyrosine Kinase Inhibitory and Antioxidant Activity of Black Chokeberry and Bilberry Fruit Extracts Rich in Chlorogenic Acid.

Edible berries such as the fruits of black chokeberry (Aronia melanocarpa (Michx.) Elliott) and bilberry (Vaccinium myrtillus L.) are considered to be rich in phenolic compounds, which are nowadays attracting great interest due to their promising health benefits. The main objective of our study was to investigate, for the first time, their inhibitory properties on Src tyrosine kinase activity, as this enzyme plays an important role in multiple cellular processes and is activated in both cancer and inflammatory cells. In hydroethanolic fruit extracts, 5.0-5.9% of total polyphenols were determined spectrophotometrically, including high amounts of hydroxycinnamic acid derivatives. HPLC analysis revealed that the black chokeberry and bilberry extracts contained 2.05 mg/g and 2.54 mg/g of chlorogenic acid, respectively. Using a time-resolved fluorescence resonance energy transfer (TR-FRET) assay, the extracts studied were found to have comparable inhibitory effects on Src tyrosine kinase, with IC50 values of 366 µg/mL and 369 µg/mL, respectively. The results also indicated that chlorogenic acid contributes significantly to the observed effect. In addition, both fruit extracts exhibited antioxidant activity by scavenging DPPH and NO radicals with SC50 values of 153-352 µg/mL. Our study suggested that black chokeberry and bilberry fruits may be beneficial in cancer and other inflammation-related diseases.