Matrigel assay using human microvascular endothelial cells showed that OptiBerry impaired angiogenesis. In an in vivo model of angiogenesis, OptiBerry significantly inhibited basal MCP-1 and inducible NF-κB transcriptions.

In essence, these studies highlight the novel anti-angiogenic, antioxidant, and anti-carcinogenic potential of a novel anthocyanin-rich berry extract formula, OptiBerry. This is a preview of subscription content, log in via an institution to check access. Rent this article via DeepDyve.

Institutional subscriptions. Francis, E. Food Sci. Google Scholar. Roy, S. Xue, H. McCarty, M. Hypotheses , 56 , — Kresty, L. Ofek, I. Willett, W. Health Perspect. Harborne, J. Aruoma, O. Bagchi, D.

Tapiero, H. Amouretti, M. Bettini, V. Narayan, M. Fatty Acids , 60 , 1—4. Camire, M. Lancaster, PA, pp. Cao, G. Waterhouse, A. Brouillard, R. Yasmin, T. Giavazzi, R.

Griffioen, A. Detmar, D. Ponce, M. Folkman, J. Lippincott-Raven, PA, pp. Boye, E. Salcedo, R. Atalay, M. Paper, D. Jiang, C. Fotsis, T. Download references. Department of Pharmacy Sciences, Creighton University Medical Center, California Plaza, Omaha, NE, , USA.

Laboratory of Molecular Medicine, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, W. Department of Physiology, University of Kuopio, P.

Box , FIN, Kuopio, Finland. You can also search for this author in PubMed Google Scholar. Correspondence to D. Reprints and permissions. et al. Anti-angiogenic, Antioxidant, and Anti-carcinogenic Properties of a Novel Anthocyanin-Rich Berry Extract Formula.

Biochemistry Moscow 69 , 75—80 Download citation. The instability, high reactivity and low extraction possibility limit their potential applications of ACNs in food and pharmaceutical industries Castañeda-Ovando et al.

Due to its high demand of energy and high lipid content, the central nervous system CNS , especially the brain, is particularly susceptible to excessive reactive oxygen species ROS Nussbaum et al. A high production of oxygen leads to a high production of intracellular ROS during cellular respiration within mitochondria Salehi et al.

In addition, exogenous sources of ROS may be environmental pollution, smoking, unhealthy diet, UV-B radiation, drug metabolites and infections Singh et al. In the CNS, a specific innate immune system, consisting of resting or activated glial cells, protects the nervous system against pathogens or injuries, but an excessive or prolonged inflammatory response may contribute to neuronal apoptosis and may facilitate the progression of neurodegenerative diseases Russo and Mcgavern, Figure 2 Summarized scheme of the most important pharmacological properties and molecular mechanisms of action of anthocyanins.

Many dietary ACNs contain multiple ACNs compounds with neuroprotective effects. Dietary ACNs from blue corn protected brain from the mitochondrial DNA common deletion mtDNA CD induced by a moderate ethanol consumption Demeilliers et al.

Finally, we showed that the administration of ACN-rich purple corn extract has a protective effect on the development of orofacial allodynia in an in vivo model of inflammatory trigeminal pain, and that it reduces trigeminal macrophage infiltration and microglial activation both in vivo and in vitro Magni et al.

The neuroprotective effect of purple corn is comparable to the antiinflammatory effects of acetyl salicylic acid, which does not modify microglia activation. Therefore, a possible application of ACN-rich dietary supplements as co-adjuvant therapy to pharmacological treatment or as a preventive strategy against trigeminal pain, aimed at reducing drugs dosage and adverse effects might be proposed.

These are a group of chronic diseases characterized by a progressive loss of neurons in brain or spinal cord, leading to a progressive impairment in cognitive and motor functions and ultimately resulting in severe disability Calina et al.

Neurodegenerative disorders and cerebral ischemia are associated to three common factors triggering the onset of neuronal apoptosis, Jellinger, ; Li et al. oxidative stress. Oxidative stress is due to a significant reduction in the ability of neuronal cells to scavenge excessive ROS, leading to oxidative damage of macromolecules i.

DNA oxidation, protein carbonylation, and lipid peroxidation and to mitochondrial dysfunction, additional generation of ROS and neuronal apoptosis Mariani et al. Increased oxidative stress and mitochondrial dysfunction precede the deposition of neurotoxic amyloid-β Aβ protein aggregates, a typical hallmark of AD Salehi et al.

They also cause the formation of the Lewy bodies, insoluble inclusions mainly consisting of damaged α-synuclein, associated with neuron loss and dopamine deficiency in the substantia nigra of PD patients Wang et al. Excitotoxicity is a common pathogenic factor in neurodegenerative diseases Dong et al.

Excitotoxicity consists of the overstimulation of glutamate receptors [i. This calcium overload triggers intracellular signaling cascades, leading to mitochondrial depolarization, increased ROS and nitric oxide NO production, degradation of macromolecules and ultimately apoptosis, thus indicating the existence of a link between excitotoxicity and oxidative stress Dong et al.

Upregulation of NMDA receptors has been associated to Aβ deposition in AD Parameshwaran et al. Neuroinflammation may be also triggered as a response to the aberrant deposition of protein aggregates, such as Aβ in AD, α-synuclein in PD and DNA-binding protein in ALS TDP Zhang et al. This is a condition in which the brain does not receive enough blood to meet its metabolic needs.

Thus, the resulting lack of oxygen can cause the death of brain tissue and therefore an ischemic stroke Tsatsakis et al. Cerebrovascular ischemia causes loss of neurons in localized regions of brain by mechanisms similar to those in neurodegenerative diseases Chen et al.

Oxidative stress caused by reperfusion following cerebrovascular ischemia triggers the production of excessive superoxide radicals by mitochondria with increasing ROS and mitochondrial dysfunction. These superoxide radicals combined with NO, produced by ischemia-induced neuronal NO synthase nNOS , generate reactive nitrogen species i.

peroxynitrite that further damage neuronal cellular proteins by nitrosylation Eliasson et al. Excitotoxicity is also a pathogenic factor in cerebrovascular ischemia. Massive release of presynaptic glutamate caused by cerebrovascular ischemia causes a consequent increase in NMDA post-synaptic receptors Szydlowska and Tymianski, ; Li Y.

et al. Neuroinflammation in cerebral ischemia: neurons injured by cerebral ischemia release cytokines and chemokines, that activate resting microglial cells to secrete antiinflammatory neuroprotective cytokines, in order to assist in repairing neuronal cells, but also to promote the synthesis of proinflammatory cytokines e.

IL-1β and TNF-α , iNOS and the production of NO, a reactive molecule which destroys invading pathogens Di Filippo et al. In case of prolonged production, the inflammatory response may result in neuronal damage and finally in apoptosis Block and Hong, These studies have reported the neuroprotective effect of ACNs in preclinical models of neurodegenerative diseases by multiple mechanisms Tsuda, ; Ullah et al.

The neuroprotective effect is accomplished because of rapid absorption of ACNs and their capacity to cross the blood brain barrier BBB. Since they can reach the brain in their native form, ACNs can exert their antioxidant activity as direct scavengers of ROS Shih et al.

They can also activate the antioxidant response by promoting the nuclear translocation of nuclear factor erythroid 2—related factor 2 Nrf2 or by stimulating the activity of antioxidant enzymes, such as SOD, CAT and GPx Casedas et al. In vitro studies have demonstrated that ACNs prevent the intracellular calcium overload, thereby causing excitotoxicity and the progression of neurodegenerative diseases Ye et al.

Inhibit the nuclear translocation of NF-κB, thereby preventing the activation of proinflammatory molecules, such as COX-2, iNOS, IL-1β, TNF-α Kim et al. Reduce the intracellular signaling pathways of mitogen-activated protein kinases MAPKs : c-Jun N-terminal kinase JNK and P38 mitogen-activated protein kinases p MAPK , also reducing the activation of proinflammatory cytokines Amin et al.

Antiinflammatory effect, by inhibiting the activity of COX-2 enzyme Mulabagal et al. Prevent the release of apoptosis-inducing factor AIF from mitochondria and its migration into the nucleus, where it triggers DNA fragmentation by a caspase-independent pathway Min et al.

to increase the expression of the proapoptotic factor B cell lymphoma-2 Bcl-2 ,. to reduce the expression of the antiapoptotic factor B-cell lymphoma protein associated X Bax Ali Shah et al.

These have proved that ACNs can prevent the onset and progression of neurodegenerative diseases as well as that they can improve learning and memory in aging model mice. The first evidence of the neuroprotective effect of ACNs was obtained when 19 months-old aged rats comparable to 60 years old humans fed with blueberry extracts for 8 weeks showed a significant improvement in motor function in the accelerated rotarod test and effectively reversed age-related deficits in neuronal and cognitive function in a test of learning and memory, such as the Morris water performance Joseph et al.

More recently, similar results were obtained in galactose-induced aging models or aged rats fed with ACNs, showing a delayed age-related decline in spatial learning and memory Andres-Lacueva et al.

Since then, it was shown that dietary ACNs from mulberry extracts applied to a senescence-accelerated mouse model of AD SAMP8 reduced Aβ plaques and improved learning and memory ability in avoidance response tests, by activating the Nrf2-dependent antioxidant defense system Shih et al.

Using an Aβ-induced model of AD in rats, intragastrically applied ACNs from black soybean were shown to reverse Aβ-induced neuronal apoptosis by suppressing protein expression of intrinsic apoptotic pathway Bax, cytochrome C, caspase-9 and caspase-3 Badshah et al.

ACNs prevent apoptosis and neurodegeneration by suppressing the activation of caspase As a result, memory-related pre- and post-synaptic protein markers and memory functions in both Morris water maze and the Y-maze tests were improved Ali et al.

Concerning Parkinson Disease, an interesting epidemiological study highlighted that a regular intake of ACNs, based on consuming strawberries and blueberries, results in a significantly lower PD risk Gao et al.

In a MPTP-induced mouse model of PD, oral supplementation of ACNs from a mulberry extract showed a significant reduction in bradykinesia, in loss of dopaminergic neurons in substantia nigra and in depletion of dopamine depletion, related to a reduced expression of the proapoptotic Bax protein Kim et al.

Studies in rotenone-induced cell models of PD suggest that ACNs attenuate mitochondrial dysfunction by reducing the rotenone-induced damage of mitochondrial complex I of the electron transport system, and reduce neuroinflammation resulting from microglial activation, thus preserving dopaminergic neurons Strathearn et al.

Only one study assessed the potential of ACNs in preventing the onset and progression of ALS, characterized by loss of motor neurons in brain, brainstem and spinal cord Winter et al.

Oral administration of an ACN-rich extract from strawberries in a mouse model of ALS, carrying a G93A mutation in the human SOD1 gene hSOD1 G93A , modestly but significantly delayed the onset of ALS about 17 days and extended the survival about 11 days when to untreated hSOD1 G93A mice, in which ALS onset occurred at about 90 days of age and progress to end-stage of disease at about days age.

Supplementation with ACNs significantly preserved grip strength and neuromuscular junctions in gastrocnemius muscle, but did not prevent motor neuron loss in spinal cord. On the other hand, a significant reduction in neuroinflammation i. activated astrocytes was observed in spinal cord Winter et al.

Multiple sclerosis MS is a result of a neuronal demyelination process and not neuron loss, but shares some common pathological mechanisms with neurodegenerative diseases Padureanu et al. Recent studies have highlighted that ACNs have a protective effect on the onset and progression of MS by reducing oxidative stress, neuroinflammation and the activity of ion pumps.

Carvalho et al. ACNs reduced demyelination in a rat model of MS by restoring glutathione level and SOD activity, suggesting that a possible Nrf2-mediated antioxidant mechanism of protection may occur Carvalho et al.

Other neuroprotective effects of ACNs were recently demonstrated in animal models of neurotoxicity or inflammatory pain. Antioxidant defense in cerebral ischemia: ACNs promote activation of Nuclear factor erythroid 2-related factor 2 Nrf2 and the consequent increase in the expression of the Heme oxygenase - 1 HO - 1 and γ-glutamyl cysteine synthase γ-GCS genes, contributing to decrease brain levels of superoxide and lipid peroxidation Min et al.

Figure 3 In cerebral ischemia, anthocyanins ACNs reduce neuroinflammation by: i decreasing the expression of Toll-like receptor 4 TLR4 , an activator of nuclear factor kappa B NF-κB , and tumor necrosis factor-α TNF-α proinflammatory cytokine expression Cui et al.

ii Reducing the expression of inducible nitric oxide synthase iNOS and neuronal nitric oxide synthase nNOS , targets of NF-κB, and as a consequence NO content at cerebral level, thus reflecting a reduction in brain damage Di Giacomo et al.

A significant increase of eNOS was observed which may result in vasorelaxation with a consequent attenuation of the ischemic insult and promotion of functional recovery of the ischemic zone Di Giacomo et al. ii Direct antiapoptotic role, since they partially blocked AIF, but not cytochrome c release from mitochondria, thus indicating that guanine nucleotide exchange factor C3G reduced apoptosis by suppressing a caspase-independent pathway Min et al.

This complex inhibits caspase-1, IL-6 and IL-1β activation, thereby inhibiting apoptosis and inflammatory responses and reducing brain damage Cui et al. These studies have shown the neuroprotective effect of ACNs in rat or mouse models of cerebral ischemia and defined some of the possible mechanisms of protection Zhang et al.

On the other hand, both pre-treatment 1h and post-treatment i. The beneficial effects of dietary ACNs in the prevention of CVDs were shown by several epidemiological studies.

Preventive effects of dietary ACNs concerning hypertriglyceridemia, hypercholesterolemia total cholesterol and LDL-cholesterol and platelet hyperactivity were reported in rat models of atherosclerosis induced by high-fat or high-fructose diets Guo et al. Similar results on CVD-related biomarkers were obtained in several human intervention studies on patients taking berries or purified ACNs, showing significantly increased HDL-cholesterol, reduced LDL-cholesterol, triglycerides, blood pressure, flow-mediated dilation and inflammatory markers García-Conesa et al.

Other studies suggested an inverse correlation between high ACN consumption and CVD-related risk biomarkers, such as lower arterial stiffness and blood pressure Cassidy et al. The cardioprotective effect of dietary ACNs may be attributed to: increase in plasma antioxidant capacity and NO levels; reduction of LDL oxidation and platelet aggregation Erlund et al.

On the contrary, high concentrations of ACNs resulted in a cardiotoxic effect, indicating a concentration-dependent cardioprotection of bilberry ACNs Ziberna et al.

The cardioprotective activity is mediated by direct intracellular transport of C3G by the bilirubin-specific plasma membrane transporter bilitranslocase, as demonstrated by the lack of cardioprotective activity of C3G when antibodies against bilitranslocase were used before ischemia reperfusion.

This shows that the entry of C3G or other ACNs into the endothelium is necessary to interact with intracellular targets and trigger an antioxidant response in cells or isolated organs Ziberna et al. Among CVDs, myocardial infarction, ischemic heart disease and stroke are primarily caused by atherosclerotic plaques, progressively growing and causing arterial stenosis or obstruction or eventually plaque rupture and thrombus formation Sharifi-Rad J.

The process of atherosclerosis is mainly caused by oxidized low-density lipoproteins oxLDL , typically associated to elevated plasma total- and LDL-cholesterol levels.

LDL particles adhere to arterial walls and enter into the intima where they are retained and where resident macrophages and macrophages originating from circulating monocytes which bind to adhesion molecules and also enter the intima phagocytize them.

Macrophage activation involves ROS production, which in turn triggers the activation of NF-κB and thereby proinflammatory cytokines and adhesion molecules causing also endothelial dysfunction. As a consequence, endothelial cells express on their surface intercellular adhesion molecule-1 ICAM-1 and vascular adhesion molecule-1 VCAM-1 , thus attracting monocytes from the bloodstream.

The progression of atherosclerotic plaques involves further lipid accumulation from LDL particles, but also migration of smooth muscle cells from media to intima and their proliferation, collagen deposition, which then form a fibrous cap which covers the lipid core of the plaque.

In advanced lesions, macrophage foam cells undergo apoptosis but are not effectively cleared by macrophages defective efferocytosis , initiating a secondary cellular necrosis process and overtime to the formation of a necrotic lipid core Moore and Tabas, Inflammatory cells at the shoulders of the plaque cause the release of collagenases and elastase from the foam cells which might cause rupturing of the atheroma fibrous cap, platelet aggregation and thrombus formation.

Prevention of atherosclerosis using apolipoprotein E apoE -deficient mice, a model characterized by hypercholesterolemia and plaques on aorta with morphological features similar to human advanced atherosclerotic lesions,.

Concerning the apo E-deficient mice, supplementation of ACN-rich diet, extracts or ACN metabolites e. In apoE-deficient mice, ACN supplementation protects LDL-cholesterol from oxidation, as proven by reduced levels of serum anti-oxLDLs Xia et al. The reduced formation of oxLDLs may be partly accomplished by a direct scavenging activity of ACNs embedded in cellular membranes or in the cytosol of endothelial cells, where they are transported by a bilitranslocase transporter Youdim et al.

Lower levels of oxLDLs resulted in lower expression of VCAM-1 and ICAM-1 in aorta Wang et al. Nevertheless it was unable to sustain this cardioprotection since cardiac dysfunction was not significantly improved after 8 weeks Raj et al.

Physiological doses of ACNs were also effective against cardiotoxicity induced by the chemotherapeutic drug doxorubicin Dox since in mice fed with dietary ACNs from purple corn treated with Dox, medium-term but not long-term survival was improved, and Dox-induced cardiac histopathological alterations were prevented when compared to animals fed with ACN-free diet from yellow corn Petroni et al.

Obesity is the result of the accumulation of adipose tissue, and it causes many metabolic disorders. A healthy lifestyle and a diet rich in ACNs have beneficial antiobesity effects Parveen et al.

One mechanism by which dietary ACNs could act as antiobese effect is the increase of energy expenditure. In adipose tissue, a reduction in mitochondrial respiration and dissipation of the mitochondrial proton gradient proton leak were also reported Skates et al. Malvidin decreases the lipopolysaccharide LPS -induced NF-κB, activation of poly ADP-ribose polymerase, MAPK, depolarization of mitochondria, and generation of ROS, Bognar et al.

Another way to spend the energy is by changing thermogenesis. The upregulation of regulating uncoupling proteins UCP1 and UCP2 , in brown and white adipose tissue respectively, suppress fat accumulation in adipose tissue in case of increased dietary consumption of black soybean seed.

Kanamoto et al. AMP-activated protein kinase AMPK is one of the main regulators of energy balance. AMPK can modulate the energetic expenditure and fat accumulation in many ways: i increasing mitochondrial biogenesis, ii reducing lipid metabolism and triglyceride synthesis, iii increasing fatty acid oxidation, iv reducing hypertriglyceridemia and triglyceride storage in muscles and liver and by regulating the food intake.

It seems that dietary ACNs induce AMPK activation by increasing its phosphorylation Hardie and Ashford, ; López, ACNs from bilberry extract also increased AMPK activity in skeletal muscle and the liver.

In skeletal muscle, AMPK activation stimulated the upregulation of glucose transporter 4 GLUT4 , resulting in an increased glucose uptake and utilization.

In the liver, AMPK activation decreased glucose production, improving hyperglycemia. A decrease in liver lipid content and serum lipoproteins was achieved through upregulation of peroxisome proliferator-activated receptor PPAR α and acyl-CoA oxidase Takikawa et al.

ACNs also improved chronic diabetic complications and insulin resistance Guo and Ling, The key molecules of lipid metabolism are fatty acid synthase FAS and sterol regulatory element-binding proteins SREBPs. ACNs from different dietary sources could downregulate mRNA and protein levels of FAS and SREBP1, reducing hyperglycemia and inhibiting hepatic lipogenesis Tsuda et al.

ACNs from black soybeans were effective in preventing obesity even in normal conditions by hypothalamus modulation. A healthy diet showed a decrease in body weight and food intake when receiving daily intra-gastric administered ACNs Salehi et al. These effects seem to be mediated by neuropeptide Y and c-amino butyric acid receptor GABAB1R in the hypothalamus Badshah et al.

ACN-rich extract from black soybean decreased saturated, monounsaturated and n-6 polyunsaturated fatty acid levels in subcutaneous but not visceral fat. Since these long-chain fatty acids play a role in inflammation regulation, their reduction could help in suppressing inflammation in obese subjects Sato et al.

Finally, ACNs seem to affect gut microbiota as well. The change in microbiota in obese people might contribute to the development of obese-related metabolic disorders.

A recent review examined the role of ACNs in obesity regulation by gut microbiota modulation Jamar et al. Considering the antidiabetic role of ACNs, they provide protection to pancreatic β cells INS-1 against H 2 O 2 -induced necrosis and apoptosis in a time- and concentration-dependent way. The supplementation with a daily intake of 4 cups of freeze-dried strawberry beverage during 8 weeks in 27 diabetic subjects caused a reduction in total and LDL-cholesterol levels as well as inhibition of VCAM-1 circulating levels Basu et al.

The simultaneous use of ACNs and apple polyphenols in five postmenopausal women and 20 men showed the initial postprandial glycemic response. Both substances suppressed the early reactions 0—30 min of plasma glucose and insulin, and reduction of postprandial glycemia.

Insulin and incretin excretion were reduced as the secondary results Castro-Acosta et al. ACNs consumption during 12 weeks also modulated the lipids and glucose-metabolism, and had antioxidant and antiinflammatory effects l in 37 humans with metabolic syndrome Kim et al.

In addition, ACNs rich beverages lowered the concentrations of interferon-γ IFN-γ and urinary level of 8-isoprostane Kim et al. Wu et al. ACNs improved glucose tolerance, enhanced insulin sensitivity and decreased hepatic accumulation of lipids via modulating the AMPK activity and lipid metabolism-associated gene expression Overall et al.

The number of obese people is dramatically increasing worldwide, affecting every year an increasing number of adults, but also children and adolescents Xie et al.

Obesity is closely related to a decrease in life expectancy and an increase in healthcare expenditures, it is a risk factor for many diseases such as some types of cancer, diabetes mellitus and CVDs Swinburn et al. The localization of the accumulated fat is crucially important: intraabdominal fat is mainly responsible for the development of the metabolic syndrome MS , which is defined as the combination of impaired glucose tolerance or diabetes mellitus, insulin resistance, high blood pressure, atherogenic dyslipidemia, and obesity Engin, The effects of ACNs on MS have been recently highlighted Naseri et al.

Increase in energy expenditure, and regulation of lipid metabolism. reduction of fat absorption. suppression of food intake. gut microbiota modification. In the treatment of LPS-activated human umbilical vein endothelial cells HUVECs , pelargonidin inhibited LPS-induced barrier disruption, migration of neutrophils to human endothelial cells, and expression of cell adhesion molecules CAMs and adhesion.

Blueberry ACN extract malvidin, malvidinglucoside, and malvidingalactoside has effects on high glucose-induced injury in human retinal capillary endothelial cells HRCECs by multiple pathways such as enhancement of cell viability, reduction of ROS, suppression of Nox4 expression, increase in enzyme activity of CAT and SOD, inhibition of Akt pathway, reduction of VEGF level, suppression of high glucose-induced intercellular adhesion molecule-1 and NF-κB, Huang et al.

The administration of µM H 2 O 2 in WI human diploid fibroblasts showed enhanced lipid peroxidation, lowered cell viability, and shortened cells lifespans. In contrast, cyanidin supplementation suppressed oxidative stress via cell viability enhancement and lipid peroxidation inhibition.

Cyanidin treatment also enhanced the cells life spans, decreased the NF-κB expression at mRNA and protein level, as well as iNOS, and COX-2 Choi et al. Recent studies showed that pelargonidin inhibited LPS-induced hyperpermeability and leukocytes migration.

In addition, pelargonidin resulted in suppressing LPS-induced lethal endotoxemia Lee et al. Increased AMPK activity has been shown in 3T3-L1 cell line treated with C3G Guo et al. In these studies, AMPK activation was accompanied by a lack of increase in LDL-cholesterol and triglycerides but with an improved serum lipids profile and inhibited accumulation of triglycerides in the liver Hwang et al.

Pure ACNs and ACN extract were able to reduce the body and liver weight, the triglycerides accumulation in the liver and the adipocyte size in mice treated with HFD Jayaprakasam et al. Blueberry-derived ACNs were effective in reducing body weight and serum glucose and in improving lipid profile in high-fat-fed mice Wu et al.

A very recent study analyzed the effect of ACNs supplementation from Sango sprout juice SSJ in obese rats. The results showed that supplementation of SSJ is more effective causing positive effects on liver, ileum and prostate when compared with a switch from a HFD to a regular.

Moreover, the SSJ supplementation together with the diet switch is more effective in respect to a simple diet switch in opposing the caecal Enterococcus decrease and the Clostridium perfringens increase registered in obese animals.

These results demonstrate a potential therapeutic role of ACNs in obese-induced intestinal dysbiosis Vivarelli et al. The adipose tissue secretes various adipocytokines, i.

Supplementation of ACNs-rich grape—bilberry juice to experimental rats lowered the concentrations of cholesterol, triglycerides, resistin, and leptin. This supplementation also decreased the saturated fatty acids and increased polyunsaturated fatty acids in plasma Graf et al.

ACNs decreased the secretion of adipocytokines adiponectin and leptin and increased lipoprotein lipase LPL , PPARγ, UCP2, and adipocyte fatty acid-binding protein aP2 expression in isolated rat adipocytes Tsuda et al. Furthermore, ACNs-rich extracts have an improving effect against D-galactose-induced senescence in a mice model via lowering the uric acid level Lu et al.

ACNs have also beneficial affects against prostatic hyperplasia Jang et al. In sickle cell disease, ACNs stabilize the erythrocyte membrane and suppress the hemoglobin polymerization Mpiana et al.

These substances also have the potential to change MAPK and NF-κB stress signaling pathways Wu et al. In another study reported by Seymour et al. They have found that ACNs decreased the intraperitoneal fat weight and increased PPAR activity.

Consistent with this, supplementation of mice under HFD with an ACNs-rich extract from purple corn resulted in lower recruitment and proliferation of macrophages into crown-like structures in the adipose tissue caused by a suppression of NF-kB signaling.

Besides attenuating adipose tissue inflammation in vivo , ACNs also showed a long-lasting reprogramming of adipose tissue macrophages and adipocyte profiles toward the antiinflammatory phenotype Tomay et al. Alteration in genes expression involved in lipid metabolism protect the induced fatty acid oxidation, and decrease the in vivo biosynthesis of fatty acids and cholesterol Wu et al.

ACNs extracts from different natural sources were able to decrease the oxidative stress. Figure 2 Dietary ACNs are known to be more effective antioxidants than vitamins E and C Rice-Evans et al.

ACNs can modulate the antioxidant defense mechanisms, activate antioxidant enzymes and promote glutathione synthesis. They are capable of chelating metal ions, such as iron and copper, thus reducing the production of free radicals by Fenton and other reactions Jomova and Valko, Several studies showed that ACNs activate nuclear factor erythroid 2-related factor 2 Nrf2 and the antioxidant enzymes, such as superoxide dismutase SOD , catalase CAT , glutathione peroxidase GPx as well as directly enhance their enzymatic activity Speciale et al.

ACNs are also able to oppose the harmful action of toxic agents. ACNs from blueberry extract suppress the effects of acrylamide, attenuating ROS overproduction and glutathione depletion in liver. They were also effective in inhibiting cytochrome P 2E1 CYP2E1 protein expression in acrylamide-treated mice.

CYP2E1 is the first protein involved in acrylamide epoxidation that was shown to cause different toxic effects Zhao et al.

The inhibition of CYP2E1 protein is also involved in the ACN-mediated protection of ethanol- and ROS-mediated damage. Ethanol, in fact, activates CYP2E1 that causes ROS production and antioxidant defense mechanisms impairment; ACNs in Gynura bicolor Roxb.

ex Willd. restored the glutathione content and decreased the ROS and glutathione disulfide levels in livers of ethanol-treated mice by reduction of CYP2E1 activity Yin et al.

Oxidative stress occurs when reactive oxygen and nitrogen species production ROS and RNS exceeds the antioxidant mechanisms of cells or tissues, thus resulting in damage of macromolecules i. proteins, lipids and DNA in chronic diseases and aging process. Acute inflammation is the primary response against injury and pathogens, and it is usually followed by the resolution of inflammation Salehi et al.

Chronic inflammation resulting from the failure of resolution is reported to promote the progression of many chronic diseases, such as CVDs, neurodegenerative diseases, diabetes mellitus and cancers Pham-Huy et al.

ACNs suppress the activation of the nuclear factor kappa B NF-κB , a transcription factor regulating many genes in inflammatory response, such as inducible NO synthase iNOS , cycloxygenase-2 COX-2 and proinflammatory cytokines [tumor necrosis factor-α TNF-α , interleukin IL -1β and IL-6] Tsuda et al.

ACNs inhibit the mitogen-activated protein kinase MAPK signaling cascade involving p38, JNK, and ERK, also inducing suppression of proinflammatory cytokines, iNOS and COX-2 Hou et al.

ACNs directly inhibit COX-1 and COX-2 enzymes and as a consequence of this, the production of prostaglandin E2 PGE2 Graf et al. The NLRP3 inflammasome is a multimeric protein complex that initiates an inflammatory form of apoptosis, by triggering the release of proinflammatory cytokines IL-1β, IL and caspase-1 and has been implicated in several diseases Yang et al.

The antioxidant activity of ACNs is well known for decades. Pojer et al. A purple sweet potato color PSPC prevents the HFD-induced endoplasmic reticulum-mediated oxidative stress in mice liver. PSPC improved the hepatic redox state of mice treated with HFD by suppressing ROS production and by restoring the glutathione content and the activity of antioxidant enzymes Zhang et al.

Similar results were observed in mice under HFD supplemented with ACNs from cherry or mulberry. Significant increases in SOD and GPx activities were detected. It was shown that monoglycoside ACNs might have higher antioxidant effects than di-glycoside or tri-glycoside ACNs Wu et al.

Cyanidin 3-glucoside C3G was efficient in reducing the oxidative stress induced by lipid peroxidation, neutrophiles infiltration, and hepatic steatosis in diabetic mice. C3G increased glutathione synthesis by the induction of the glutamate-cysteine ligase catalytic subunit mediated by protein kinase A PKA and cAMP-response-element binding protein CREB Zhu et al.

ACNs can improve ROS-caused damage in the brain. ACNs from Korean black bean inhibited ROS production induced by ethanol in the hippocampus of the postnatal rats Shah et al. ACNs from black soybean suppressed neuroinflammation and neurodegeneration caused by oxidative stress and ROS increase in the cortex of adult mice Khan et al.

ACNs have attracted interest in the last several decades as potential antitumoral agents Pojer et al. There are several pathways involved in cancer, and some of them are not yet explained. Dietary berry ACNs can modulate the levels of Notch1 and Wnt1 proteins and their downstream mediators.

In particular, ACNs mixture showed an enhanced reduction of all the proteins when compared with the single purified ACNs, indicating that some pathways may overlap in the induction of cell growth inhibition Kausar et al. The ACNs-mediated cancer prevention and inhibition mainly includes pathways involved in cell survival, proliferation, apoptosis control and inflammation.

Although inflammation and oxidative stress play an important role in cancer progression Kristo et al. In contrast, the glucosidic part may reduce the beneficial properties and interactions Song et al. Still, if activated, it can cause deregulation of cell growth, malignant transformation and, often, therapy resistance Hennessy et al.

NF-κB has been indicated as the mediator between chronic inflammation and cancer. It can regulate tumor angiogenesis, metastatic process and apoptosis inhibition Salehi et al.

It has been suggested as a possible target in cancer therapy, even if its prolonged inhibition can cause deleterious effects Xia et al. The main problem with chemotherapy is that some cancers can develop resistance to treatment after several months. Angiogenesis, metastasis progression and cell migration can severely worsen the patient status and compromise the success of chemotherapy Mishra et al.

Trastuzumab Herceptin ® is a recombinant humanized monoclonal antibody that is targeted against human HER2 tyrosine kinase receptor, and it has been successfully used to treat patients with HER2-positive breast cancer. However, some trastuzumab-treated patients, who initially responded well, showed disease progression within a year after the end of the treatment Li X.

C3G can enhance trastuzumab Liu et al. Inhibition of tumor growth. promoting apoptosis and autophagy of malignant cells. modulating signal transduction pathways. inhibition of angiogenesis and metastatic migration.

antiinflammatory and antioxidant properties. Delphinidin, a substance belonging to ACNs, dose-dependently suppresses cell proliferation and invasion, it induces apoptotic cell death and autophagy in human epidermal growth factor receptor HER -2 positive breast cancer MDA-MB and BT cells.

Moreover, it causes induction of autophagy via inhibiting mTOR signaling pathway and activation of the AMPK signaling pathway in HER-2 positive breast cancer cells Chen J. In a recent study by Zhou et al. ACNs significantly inhibited the migration and cell invasion, lowered the migration distance of HER-2 positive human breast cancer cells, phosphorylation of cSrc, FAK, and pC, lowered the levels of mesenchymal markers fibronectin, vimentin , decreased the interaction between HER-2 and FAK, FAK and cSrc, and inhibited the epithelial-mesenchymal transition Zhou et al.

The antitumor effect of ACNs in human hepatoma cells SMMC and the murine hepatoma cells H22 studies were also highlighted.

It achieves it by inhibiting the vascular endothelial growth factor VEGF expression and secretion, by decreasing the activator of transcription 3 STAT3 and signal transducer expression at both mRNA and protein level. Additionally, induction of miR expression was also reported after ACNs treatment Salehi et al.

A study conducted by Mazewski et al. They have confirmed all these effects. In another study, ACNs in a human gastrointestinal model Colonic Caco-2 cancer cells and nontumorigenic colonic CCDCoN cells cause cytotoxicity and lower cell viability Kubow et al.

Kuntz et al. In another study conducted by Giampieri et al. Cyanidin 3-rutinoside can inhibit the motility of RKO human colon cancer cells, as demonstrated by a wound-healing assay Fragoso et al. Moreover, VEGF-induced angiogenesis was strongly inhibited by black raspberry extract on two organ-specific primary cells [i.

human intestinal microvascular endothelial cells HIMEC and human esophagal microvascular endothelial cells HEMEC ], isolated from surgically resected human intestine and esophagus Medda et al. ACN extract of roselle Hibiscus ACNs was supplemented in the diet of the rat model of N-methyl-N-nitrosourea NMU -induced leukemia, and it significantly reduced the elevated aspartate aminotransferase AST and alanine aminotransferase ALT levels in serum and blood, and prevented NMU-induced leukemic cell infiltration and subsequent tissue damage Tsai et al.

Not only ACNs but also their metabolites can prevent tumor growth Peiffer et al. In the same study protocatechuic acid, a major metabolite of blackberry ACNs, was able to reduce esophagal carcinogenesis in N-nitroso methyl benzylamine NMBA -induced rats carcinogenesis.

They also provoked the death of tumor cells, inhibited tumor growth, and improved the survival status of H22 tumor-bearing mice. These effects were associated with an increase of the antioxidant mechanism SOD, GPx, and glutathione and a decrease of the lipid peroxidation MDA.

The levels of immune cytokines, including IL-2, IFN-γ, and TNF-α, were also regulated by ACNs Zhou et al. and Enterococcus spp. These substances caused demethylation of the secreted frizzled related protein 2 SFRP2 gene promoter, resulting in an increased expression of SFRP2, both at the mRNA and protein levels.

In addition, they also down-regulated the DNMT31 and DNMT3B, and p-STAT3 expression Chen L. Topical application of C3G can also reduce COX-2 levels and NF-κB activation in the skin of UV-B exposed mice Pratheeshkumar et al.

There is a great interest in general public in the consumption of colorful phytochemicals such as ACNs, carotenoids and flavonoids, which are present in food and dietary supplements as well as in nutraceuticals.

Polyphenolic substances, including flavonoids, are one of the most important classes of natural compounds that have a remarkable biological activity Sharifi-Rad et al. Phenol-derived compounds including polyphenols, flavonoids and anthocyanidins have been recognized among the most promising secondary metabolites of naturally occurring compounds with therapeutic potentials.

ACNs could be directly absorbed and found in animal or human plasma, while anthocyanidins have low bioavailability. The increased number of attached sugars in the aglycon might negatively affect the binding ability of ACNs to different targets Sogo et al. The main limitation in clinical therapy emerge from the low bioavailability of ACNs Czank et al.

These aspects suggest that ACNs mainly accomplish their role of direct scavengers in the gut. In order to improve the bioavailability and clinical usage of ACNs, chemical modifications and new drug design, such as nanotechnology were developed Braga et al.

Cyclodextrins are part of the most used class receptors in host-guest inclusion chemistry. However, they can function as molecular signals, being able to activate the endogenous antioxidant defense mechanisms Virgili and Marino, Nanoencapsulation is an example of a new research possibility that allows enhancing the bioavailability and optimizing the delivery of phytochemicals Khan H.

Advantages of nanoencapsulation are: preservation of flavor, enhancing thermal and oxidative stability of chemical compounds, overcoming the limitations of high volatility, controlling the release of substances and improving bioavailability. Nanoencapsulation is more efficient and has better encapsulation properties than microencapsulation.

All of these characteristics increase the possibilities of applications of phytochemicals in food and beverages. Wyspianska et al. The combination of carriers, e. ACNs are hydrophilic natural chemical substances and cannot cross the plasma membrane by passive diffusion.

Therefore, they need a hydrophilic carrier Walton et al. Their bioaccessibility potential is also depending upon their mineral contents, particularly potassium. In vitro digestion procedures can be used to evaluate the bioaccessibility Gomes et al.

Usually are used gastric simulation and small intestinal digestion models, sometimes followed by Caco-2 cells uptake Vaidyanathan and Walle, The preparation parameters of nanocomplexes with chitosan hydrochloride, inulin, and carboxymethyl chitosan as carrier showed maximum ACNs retention rate, preferred particle size and high encapsulation efficiency.

For instance, to increase the bioavailability, the ACN source was encapsulated with liposomal micelles. The taste, smell and color of ACNs became more acceptable to consumers with encapsulation of isotonic drinks and extracts of fruits.

Besides, the beverages enriched with inulin microcapsules had also better stability during storage Tarone et al. The main clinical pitfall of ACNs therapeutics usage is that certain drugs interact with ACNs.

Studies have shown that the cytochrome P enzyme, which is involved in drug metabolism, is inhibited by flavonoids. An efflux transporter called P-glycoprotein, which decreases the absorption of certain drugs, is also affected. ACNs also interact with certain nutrients. They can bind to iron, thus decreasing its absorption in the intestine.

Some of ACNs also inhibit cellular absorption of vitamin C Ayabe and Akashi, ACNs are a diverse group of phytonutrients found in almost all fruits and vegetables.

Along with carotenoids, they are responsible for the vivid colors of fruits and vegetables. Anthocyanidins include malvidin, pelargondin, peoidin, and cyanidin. Good sources of anthocyanidins are red, purple and blue fruits, such as pomegranates, plums, red wine and red and black grapes.

Anthocyanidins are associated with heart health, antioxidant effects and help prevent obesity and diabetes. ACNs are also widely used as natural dyes in the food industry. They have a wide range of color tones, ranging from orange to red to purple and blue, depending on the molecular structure and pH value.

Interest in ACNs is not only based on their coloring effect, but also due to their health-beneficial properties. Due to the growing environmental and health problems in terms of synthetic dyes, natural dyes are an excellent alternative as an environmentally friendly dye for the food and drug industry.

ACNs are rapidly absorbed and appear in the bloodstream only few minutes after consumption. Future studies need to be planned to enable better understanding of the mechanisms by which food components achieve their effects and their pharmacokinetic characteristics.

Antioxidant and antiinflammatory effects of ACNs are proven and it seems that ACNs also have an important role in CVDs, neurodegenerative diseases, diabetes and cancer. The potential of ACNs to affect mammalian metabolism is demonstrated in in vitro and in vivo studies.

Dietary ACNs may be a potential regulator of obesity-derived inflammation and associated chronic diseases. Future clinical studies, using food rich in ACNs and purified ACNs need to be performed, better understand the therapeutic potential of these antioxidant substances.

Conceptualization JS-R and DC. Validation investigation, resources, data curation, writing—all authors. Review and editing—JS-R, KP, MM, AM, ŽR, and DC. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ali, T. doi: PubMed Abstract CrossRef Full Text Google Scholar. Ali Shah, S. Anthocyanins protect against ethanol-induced neuronal apoptosis via GABAB1 receptors intracellular signaling in prenatal rat hippocampal neurons.

Amin, F. CrossRef Full Text Google Scholar. Andres-Lacueva, C. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Asadi, K. Cancer-preventive Properties of an Anthocyanin-enriched Sweet Potato in the APC MIN Mouse Model. Cancer Prev. Aura, A. In vitro metabolism of anthocyanins by human gut microflora.

Ayabe, S. Cytochrome Ps in flavonoid metabolism. Badshah, H. Anthocyanins attenuate body weight gain via modulating neuropeptide Y and GABAB1 receptor in rats hypothalamus. Neuropeptides 47, — Protective effects of anthocyanins against amyloid beta-induced neurotoxicity in vivo and in vitro.

Basu, A. Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome. Berries: emerging impact on cardiovascular health.

Belwal, T. Food Chem. Block, M. Chronic microglial activation and progressive dopaminergic neurotoxicity.

Bognar, E. Antioxidant and anti-inflammatory effects in RAW PloS One 8, e Braga, A. Bioavailability of anthocyanins: Gaps in knowledge, challenges and future research.

Food Composition Anal. Buga, A. Molecular and cellular stratagem of brain metastases associated with melanoma. Calina, D. The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation—Evidence from In Vivo Studies.

Canon, B. Biochemistry To Behaviour. Nature , 3—4. Carvalho, F. Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination.

Casedas, G. Regulation of redox status in neuronal SH-SY5Y cells by blueberry Vaccinium myrtillus L. juice, cranberry Vaccinium macrocarpon A. juice and cyanidin. Cassidy, A. Habitual intake of flavonoid subclasses and incident hypertension in adults.

High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation , — Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults.

Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men. Castañeda-Ovando, A. Chemical studies of anthocyanins: A review. Castro-Acosta, M. Apple and blackcurrant polyphenol-rich drinks decrease postprandial glucose, insulin and incretin response to a high-carbohydrate meal in healthy men and women.

Chen, H. Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Redox Signal 14, — Chen, X. Chen, J.

Delphinidin induced protective autophagy via mTOR pathway suppression and AMPK pathway activation in HER-2 positive breast cancer cells.

BMC Cancer 18, Chen, L. Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation.

Carcinogenesis 39, — Chiang, A. Antioxidant effects of black rice extract through the induction of superoxide dismutase and catalase activities.

Lipids 41, — Chiva-Blanch, G. Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication. Choi, M. Anti-aging effects of cyanidin under a stress-induced premature senescence cellular system.

Choi, Y. Gut Liver 11, — Chun, O. Serum C-reactive protein concentrations are inversely associated with dietary flavonoid intake in U. Cui, H. Molecules Czank, C.

Human metabolism and elimination of the anthocyanin, cyanidinglucoside: a 13 C-tracer study. Demeilliers, C. Ethanol drinking, brain mitochondrial DNA, polyunsaturated fatty acids and effects of dietary anthocyanins.

Di Filippo, M. Mitochondria and the link between neuroinflammation and neurodegeneration. Alzheimers Dis. Di Giacomo, C. Based Complement Alternat. Docea, A. Dong, X. Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases.

Acta Pharmacol. Dreesen, O. Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev. Eliasson, M. Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neural damage.

Engin, A. The Definition and Prevalence of Obesity and Metabolic Syndrome. Erlund, I. Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol.

Fragoso, M. Lyophilized açaí pulp Euterpe oleracea Mart attenuates colitis-associated colon carcinogenesis while its main anthocyanin has the potential to affect the motility of colon cancer cells. Gao, X. Habitual intake of dietary flavonoids and risk of Parkinson disease.

Neurology 78, — García-Conesa, M. 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.

Ge, J. Nanocomplexes composed of chitosan derivatives and β-Lactoglobulin as a carrier for anthocyanins: Preparation, stability and bioavailability in vitro. Food Res. Giampieri, F. Overexpression of the Anthocyanidin Synthase Gene in Strawberry Enhances Antioxidant Capacity and Cytotoxic Effects on Human Hepatic Cancer Cells.

Gomes, T. Differential contribution of grape peel, pulp, and seed to bioaccessibility of micronutrients and major polyphenolic compounds of red and white grapes through simulated human digestion. Foods 52, — Graf, D. Anthocyanin-Rich Juice Lowers Serum Cholesterol, Leptin, and Resistin and Improves Plasma Fatty Acid Composition in Fischer Rats.

Guo, H. The update of anthocyanins on obesity and type 2 diabetes: Experimental evidence and clinical perspectives. Endocrine Metab. Effect of anthocyanin-rich extract from black rice Oryza sativa L. indica on hyperlipidemia and insulin resistance in fructose-fed rats.

Plant Foods Hum. CyanidinO-β-glucoside, a typical anthocyanin, exhibits antilipolytic effects in 3T3-L1 adipocytes during hyperglycemia: Involvement of FoxO1-mediated transcription of adipose triglyceride lipase.

Gupta, S. Topics in heterocyclic chemistry India: Springer. Google Scholar. Ha, U. Anthocyanin Induces Apoptosis of DU Cells In Vitro and Inhibits Xenograft Growth of Prostate Cancer. Yonsei Med. Hardie, D. AMPK: Regulating Energy Balance at the Cellular and Whole Body Levels.

Physiology 29, 99— Hassimotto, N. Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidinglucoside.

Helton, T. Pruning and loss of excitatory synapses by the parkin ubiquitin ligase. Hennessy, B. Drug Discovery 4, — Hou, D.

Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure-activity relationship and molecular mechanisms involved. Hou, Y. Brain Res. Huang, W. Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells.

Cell Longev. Hwang, Y. Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through activating adenosine monophosphate-activated protein kinase in human HepG2 cells and obese mice.

Jackman, R. Anthocyanins as food colorants—a review. Food Biochem. Jamar, G. Contribution of anthocyanin-rich foods in obesity control through gut microbiota interactions. BioFactors 43, — Jana, S. Anthocyanin rich extract of Brassica oleracea L. alleviates experimentally induced myocardial infarction.

Institutional subscriptions. Francis, E. Food Sci. Google Scholar. Roy, S. Xue, H. McCarty, M. Hypotheses , 56 , — Kresty, L.

Ofek, I. Willett, W. Health Perspect. Harborne, J. Aruoma, O. Bagchi, D. Tapiero, H. Amouretti, M. Bettini, V. Narayan, M. Fatty Acids , 60 , 1—4. Camire, M. Lancaster, PA, pp. Cao, G. Waterhouse, A.

Brouillard, R. Yasmin, T. Giavazzi, R. Griffioen, A. Detmar, D. Ponce, M. Folkman, J. Lippincott-Raven, PA, pp. Boye, E. Salcedo, R. Atalay, M. Paper, D. Jiang, C. Fotsis, T. Download references. Department of Pharmacy Sciences, Creighton University Medical Center, California Plaza, Omaha, NE, , USA.

Laboratory of Molecular Medicine, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, W. Department of Physiology, University of Kuopio, P.

Box , FIN, Kuopio, Finland. You can also search for this author in PubMed Google Scholar. Correspondence to D. Reprints and permissions. et al. Anti-angiogenic, Antioxidant, and Anti-carcinogenic Properties of a Novel Anthocyanin-Rich Berry Extract Formula.

Biochemistry Moscow 69 , 75—80 Download citation. Issue Date : January Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Abstract Edible berry anthocyanins possess a broad spectrum of therapeutic and anti-carcinogenic properties. As well as acting as antioxidants and fighting those pesky free radicals, anthocyanins can offer anti-inflammatory, anti-viral, and anti-cancer properties.

In the skin they also help to deter collagen breakdown which happens naturally as we get older and leads to sagging, fine lines and wrinkles. In herbal medicine, anthocyanin-rich substances have long been used to treat a number of conditions including high blood pressure, colds, and urinary tract infections.

But it is the more recent research suggests that anthocyanins may also help fend off major health problems, including heart disease, obesity and cancer. Although it is often found in Moussaka, aubergine also makes a good alternative to fries and they go great with that remaining mayo!

Skip to content Anthocyanins are a type of flavonoid, which is a class of compounds that have some pretty badass antioxidant effects. Stir immediately for a minute or so to avoid clumping.

Add spices as you stir, along with the vanilla. Allow to stand for mins to thicken, or covered in the fridge overnight. Add berries, nuts and seeds to your liking.

Scoff that thing down in a flash.