Topical Collection "Effects of Food Antioxidants on Cardiovascular Diseases and Human Cancers"

A topical collection in Diseases (ISSN 2079-9721). This collection belongs to the section "Cardiology".

Editors

Collection Editor
Prof. Dr. Maurizio Battino

Department of Odontostomatologic and Specialized Clinical Sciences, Sez-Biochimica, Faculty of Medicine, Università Politecnica delle Marche, Via Ranieri 65, 60100 Ancona, Italy
Website | E-Mail
Phone: +39 071 2204646
Fax: +39 071 2204398
Interests: nutrition; periodontal diseases/periodontitis; oxidative stress; nutrition; aging; mitochondrial function and diseases; berries (strawberry, blueberry, bilberry, cranberry, etc.); olive oil (dietary fats); honey, polyphenols; flavonoids; antioxidants, apoptosis
Collection Editor
Dr. Esra Capanoglu

Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, 34469 Istanbul, Turkey
Website | E-Mail
Phone: + 90 212 2857340
Fax: + 90 212 2857333
Interests: antioxidants; polyphenols; flavonoids; carotenoids; bioactive peptides; in vitro bioavailability; fruits and vegetables; food processing

Topical Collection Information

Dear Colleagues,

There is a growing interest in the new diet-health paradigm, which places more emphasis on the positive aspects of our diet. This has led to nutritional studies in which foods are being analyzed for their protective and disease prevention potential. Some foods have been reported to be capable of providing additional physiological benefits, including preventing or delaying onset of a range of chronic diseases, due to their potentially health-promoting antioxidant constituents. In particular, phytochemicals with antioxidant potential are well-reported to play role in reducing the consequences of oxidative stress in disease development and the aging process, and thus contribute to the overall health-protective effects of foods particularly, fruits and vegetables. The most thoroughly-studied groups of dietary antioxidants include the carotenoids (i.e., α-carotene, β-carotene, lycopene, etc.), phenolic compounds (i.e., flavonoids), and vitamins (A, C, and E). The ingestion of these biologically active components has been correlated with the prevention and lower incidence of several degenerative diseases including cardiovascular disease and certain forms of cancer. This Topical Collection will focus on the research studies either in vitro or in vivo, investigating the effects of antioxidants on cardiovascular diseases and human cancers.

Prof. Dr. Maurizio Battino
Dr. Esra Capanoglu
Collection Editors

Manuscript Submission Information

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Keywords

  • antioxidants
  • health
  • cardiovascular diseases
  • cancer
  • in vivo studies
  • in vitro studies

Published Papers (16 papers)

2017

Jump to: 2016, 2015

Open AccessFeature PaperPerspective Flavonoids and Their Metabolites: Prevention in Cardiovascular Diseases and Diabetes
Diseases 2017, 5(3), 19; doi:10.3390/diseases5030019
Received: 2 August 2017 / Revised: 1 September 2017 / Accepted: 3 September 2017 / Published: 5 September 2017
PDF Full-text (801 KB) | HTML Full-text | XML Full-text
Abstract
The occurrence of atherosclerosis and diabetes is expanding rapidly worldwide. These two metabolic disorders often co-occur, and are part of what is often referred to as the metabolic syndrome. In order to determine future therapies, we propose that molecular mechanisms should be investigated.
[...] Read more.
The occurrence of atherosclerosis and diabetes is expanding rapidly worldwide. These two metabolic disorders often co-occur, and are part of what is often referred to as the metabolic syndrome. In order to determine future therapies, we propose that molecular mechanisms should be investigated. Once the aetiology of the metabolic syndrome is clear, a nutritional intervention should be assessed. Here we focus on the protective effects of some dietary flavonoids, and their metabolites. Further studies may also pave the way for development of novel drug candidates. Full article
Figures

Figure 1a

Open AccessReview The Role of the MAPK Signaling, Topoisomerase and Dietary Bioactives in Controlling Cancer Incidence
Diseases 2017, 5(2), 13; doi:10.3390/diseases5020013
Received: 30 December 2016 / Revised: 16 April 2017 / Accepted: 19 April 2017 / Published: 26 April 2017
PDF Full-text (2410 KB) | HTML Full-text | XML Full-text
Abstract
Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are
[...] Read more.
Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses. The oxidative stress of redundant free radicals production can lead to oxidative denaturation of cellular macromolecules including proteins, lipids and DNA. Moreover, oxidative damage is one of the major causes of DNA mutations, replication errors and genomic abnormalities which result in either inhibition or induction of transcription, and end with the disturbance of signal transduction pathways. Among affected signaling pathways are redox-sensitive kinases. The stimulation of these kinases induces several transcription factors through the phosphorylation of their module proteins. The activation of such pathways induces proliferation and cellular transformation. A diet rich in antioxidant compounds has potential health benefits, and there is a growing interest in the role of natural antioxidants in nutrition for prevention and cure of cancer diseases. A controversy has risen regarding the relation between antioxidants and the significant decrease in the risk of cancer incidence. In this review, we will focus on redox-sensitive kinases signaling pathways, highlighting the effects of dietary antioxidant on the prevention, incidence, prognosis or even treatment of human cancers. In addition, we will place emphasis on the chemical classes of pterocarpans as natural anti-oxidants/cancers as well as their underlying mechanisms of action, including their effects on MAPKs and topoisomerase activities. Full article
Figures

Figure 1

2016

Jump to: 2017, 2015

Open AccessReview The Cardiovascular Effects of Cocoa Polyphenols—An Overview
Diseases 2016, 4(4), 39; doi:10.3390/diseases4040039
Received: 12 October 2016 / Revised: 12 December 2016 / Accepted: 13 December 2016 / Published: 17 December 2016
PDF Full-text (2652 KB) | HTML Full-text | XML Full-text
Abstract
Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%–38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%–65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols
[...] Read more.
Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%–38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%–65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function. This paper reviews the role of cocoa polyphenols in cardiovascular protection, with a special focus on mechanisms of action, clinical relevance and correlation between antioxidant activity and cardiovascular health. Full article
Figures

Figure 1

Open AccessReview The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases
Diseases 2016, 4(4), 34; doi:10.3390/diseases4040034
Received: 15 September 2016 / Revised: 4 November 2016 / Accepted: 7 November 2016 / Published: 11 November 2016
PDF Full-text (675 KB) | HTML Full-text | XML Full-text
Abstract
It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However,
[...] Read more.
It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine) and epigallocatechin gallate or EGCG (in green tea) can activate the nuclear erythroid-2 like factor-2 (Nrf2) transcription factor. It is a master regulator of endogenous cellular defense mechanisms. Nrf2 controls the expression of many antioxidant and detoxification genes, by binding to antioxidant response elements (AREs) that are commonly found in the promoter region of antioxidant (and other) genes, and that control expression of those genes. The mechanisms by which Nrf2 relieves oxidative stress and limits cardiac injury as well as the progression to heart failure are described. Also, the ability of statins to induce Nrf2 in the heart, brain, lung, and liver is mentioned. However, there is a negative side of Nrf2. When over-activated, it can cause (not prevent) cardiovascular diseases and multi-drug resistance cancer. Full article
Figures

Open AccessReview Honey and Cancer: Current Status and Future Directions
Diseases 2016, 4(4), 30; doi:10.3390/diseases4040030
Received: 30 July 2016 / Revised: 16 September 2016 / Accepted: 19 September 2016 / Published: 30 September 2016
Cited by 1 | PDF Full-text (1931 KB) | HTML Full-text | XML Full-text
Abstract
Cancer is a leading cause of death worldwide and poses a challenge to treatment. With overwhelming evidence of the role played by diet and lifestyle in cancer risk and prevention, there is a growing interest into the search for chemopreventative or chemotherapeutic agents
[...] Read more.
Cancer is a leading cause of death worldwide and poses a challenge to treatment. With overwhelming evidence of the role played by diet and lifestyle in cancer risk and prevention, there is a growing interest into the search for chemopreventative or chemotherapeutic agents derived from natural products. Honey is an important source of bioactive compounds derived from plants and recent years have seen an increased interest in its anticancer properties. This review examines the role of honey in targeting key hallmarks of carcinogenesis, including uncontrolled proliferation, apoptosis evasion, angiogenesis, growth factor signalling, invasion, and inflammation. The evidence for honey as an adjunct to conventional cancer therapy is also presented. The review also highlights gaps in the current understanding and concludes that, before translation of evidence from cell culture and animal studies into the clinical setting, further studies are warranted to examine the effects of honey at a molecular level, as well as on cells in the tumour environment. Full article
Figures

Figure 1

Open AccessReview Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention
Diseases 2016, 4(3), 28; doi:10.3390/diseases4030028
Received: 28 March 2016 / Revised: 18 July 2016 / Accepted: 18 July 2016 / Published: 1 August 2016
Cited by 7 | PDF Full-text (1947 KB) | HTML Full-text | XML Full-text
Abstract
Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin Olive
[...] Read more.
Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin Olive Oil) compared to the low-fat diet group. Conversely, the increase in oxidative stress causing inflammation is a unifying hypothesis for predisposing people to atherosclerosis, carcinogenesis, and osteoporosis. The impact of antioxidants and anti-inflammatory agents on cancer and cardiovascular disease, and the interventive mechanisms for the inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis were explored. Following the Great Oxygen Event some 2.3 billion years ago, organisms have needed antioxidants to survive. Natural products in food preservatives are preferable to synthetic compounds due to their lower volatility and stability and generally higher antioxidant potential. Free radicals, reactive oxygen species, antioxidants, pro-oxidants and inflammation are described with examples of free radical damage based on the hydroxyl, nitric oxide and superoxide radicals. Flavonoid antioxidants with 2- or 3-phenylchroman structures such as quercetin, kaempferol, myricetin, apigenin, and luteolin, constituents of fruits, vegetables, tea, and wine, which may reduce coronary disease and cancer, are described. The protective effect of flavonoids on the DNA damage caused by hydroxyl radicals through chelation is an important mechanism, though the converse may be possible, e.g., quercetin. The antioxidant properties of carotenoids, which are dietary natural pigments, have been studied in relation to breast cancer risk and an inverse association was found with plasma concentrations: higher levels mean lower risk. The manipulation of primary and secondary human metabolomes derived especially from existing or transformed gut microbiota was explored as a possible alternative to single-agent dietary interventions for cancer and cardiovascular disease. Sustained oxidative stress leading to inflammation and thence to possibly to cancer and cardiovascular disease is described for spices and herbs, using curcumin as an example of an intervention, based on activation of transcription factors which suggest that oxidative stress, chronic inflammation, and cancer are closely linked. Full article
Open AccessArticle Influence of Vitamins on Secondary Reactive Oxygen Species Production in Sera of Patients with Resectable NSCLC
Diseases 2016, 4(3), 25; doi:10.3390/diseases4030025
Received: 21 April 2016 / Revised: 11 July 2016 / Accepted: 11 July 2016 / Published: 14 July 2016
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Abstract
Background: Singlet oxygen (1O2) oxidizes targets through the production of secondary reactive oxygen species (SOS). Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study was
[...] Read more.
Background: Singlet oxygen (1O2) oxidizes targets through the production of secondary reactive oxygen species (SOS). Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study was to determine the oxidative status of patients with resectable Non-Small cell lung cancers (NSCLC) and the potential influence of antioxidants, compared to sera from healthy donors. Materials and Methods: Serum samples from 10 women and 28 men, 19 adenocarcinomas (ADK), 15 patients N1 or M1 were submitted to a photoreaction producing 1O2. Then, samples were supplemented with vitamins (Vit C, Vit E), or glutathione (GSH). Results: Squamous cell carcinomas (SCC) and metastatic SCCs induced a lower SOS rate. While Vit C increased SOS in controls as in patients with metastases, Vit E or the combination of Vit E and C strongly reduced SOS. GSH alone lightly decreased SOS in controls but had no effect in patients either alone or combined with Vit C. Conclusion: In “early” lung cancers, SOS are comparable or lower than for healthy persons. The role of Vitamins varies with gender, cancer type, and metastases. This suggests that an eventual supplementation should be performed on a per-patient basis to evidence any effect. Full article
Open AccessReview The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications
Diseases 2016, 4(3), 24; doi:10.3390/diseases4030024
Received: 30 March 2016 / Revised: 20 June 2016 / Accepted: 23 June 2016 / Published: 11 July 2016
Cited by 1 | PDF Full-text (3446 KB) | HTML Full-text | XML Full-text
Abstract
Obesity and diabetes is generally accompanied by a chronic state of oxidative stress, disequilibrium in the redox balance, implicated in the development and progression of complications such as micro- and macro-angiopathies. Disorders in the inner layer of blood vessels, the endothelium, play an
[...] Read more.
Obesity and diabetes is generally accompanied by a chronic state of oxidative stress, disequilibrium in the redox balance, implicated in the development and progression of complications such as micro- and macro-angiopathies. Disorders in the inner layer of blood vessels, the endothelium, play an early and critical role in the development of these complications. Blunted endothelium-dependent relaxation and/or contractions are quietly associated to oxidative stress. Thus, preserving endothelial function and oxidative stress seems to be an optimization strategy in the prevention of vascular complications associated with diabetes. Diet is a major lifestyle factor that can greatly influence the incidence and the progression of type 2 diabetes and cardiovascular complications. The notion that foods not only provide basic nutrition but can also prevent diseases and ensure good health and longevity is now attained greater prominence. Some dietary and lifestyle modifications associated to antioxidative supply could be an effective prophylactic means to fight against oxidative stress in diabesity and complications. A significant benefit of phytochemicals (polyphenols in wine, grape, teas), vitamins (ascorbate, tocopherol), minerals (selenium, magnesium), and fruits and vegetables in foods is thought to be capable of scavenging free radicals, lowering the incidence of chronic diseases. In this review, we discuss the role of oxidative stress in diabetes and complications, highlight the endothelial dysfunction, and examine the impact of antioxidant foods, plants, fruits, and vegetables, currently used medication with antioxidant properties, in relation to the development and progression of diabetes and cardiovascular complications. Full article
Figures

Open AccessReview The Role of Glucosinolate Hydrolysis Products from Brassica Vegetable Consumption in Inducing Antioxidant Activity and Reducing Cancer Incidence
Diseases 2016, 4(2), 22; doi:10.3390/diseases4020022
Received: 11 March 2016 / Revised: 31 May 2016 / Accepted: 3 June 2016 / Published: 17 June 2016
Cited by 2 | PDF Full-text (612 KB) | HTML Full-text | XML Full-text
Abstract
The bioactivity of glucosinolates (GSs), and more specifically their hydrolysis products (GSHPs), has been well documented. These secondary metabolites evolved in the order Brassicales as plant defense compounds with proven ability to deter or impede the growth of several biotic challenges including insect
[...] Read more.
The bioactivity of glucosinolates (GSs), and more specifically their hydrolysis products (GSHPs), has been well documented. These secondary metabolites evolved in the order Brassicales as plant defense compounds with proven ability to deter or impede the growth of several biotic challenges including insect infestation, fungal and bacterial infection, and competition from other plants. However, the bioactivity of GSHPs is not limited to activity that inhibits these kingdoms of life. Many of these compounds have been shown to have bioactivity in mammalian systems as well, with epidemiological links to cancer chemoprevention in humans supported by in vitro, in vivo, and small clinical studies. Although other chemopreventive mechanisms have been identified, the primary mechanism believed to be responsible for the observed chemoprevention from GSHPs is the induction of antioxidant enzymes, such as NAD(P)H quinone reductase (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutathione S transferases (GSTs), through the Keap1-Nrf2-ARE signaling pathway. Induction of this pathway is generally associated with aliphatic isothiocyanate GSHPs, although some indole-derived GSHPs have also been associated with induction of one or more of these enzymes. Full article
Open AccessReview Targeting MicroRNA in Cancer Using Plant-Based Proanthocyanidins
Diseases 2016, 4(2), 21; doi:10.3390/diseases4020021
Received: 29 February 2016 / Revised: 11 April 2016 / Accepted: 22 April 2016 / Published: 28 April 2016
PDF Full-text (1353 KB) | HTML Full-text | XML Full-text
Abstract
Proanthocyanidins are oligomeric flavonoids found in plant sources, most notably in apples, cinnamon, grape skin and cocoa beans. They have been also found in substantial amounts in cranberry, black currant, green tea, black tea and peanut skins. These compounds have been recently investigated
[...] Read more.
Proanthocyanidins are oligomeric flavonoids found in plant sources, most notably in apples, cinnamon, grape skin and cocoa beans. They have been also found in substantial amounts in cranberry, black currant, green tea, black tea and peanut skins. These compounds have been recently investigated for their health benefits. Proanthocyanidins have been demonstrated to have positive effects on various metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. Another upcoming area of research that has gained widespread interest is microRNA (miRNA)-based anticancer therapies. MicroRNAs are short non-coding RNA segments, which plays a crucial role in RNA silencing and post-transcriptional regulation of gene expression. Currently, miRNA based anticancer therapies are being investigated either alone or in combination with current treatment methods. In this review, we summarize the current knowledge and investigate the potential of naturally occurring proanthocyanidins in modulating miRNA expression. We will also assess the strategies and challenges of using this approach as potential cancer therapeutics. Full article
Open AccessReview Effect of Dietary Bioactive Compounds on Mitochondrial and Metabolic Flexibility
Diseases 2016, 4(1), 14; doi:10.3390/diseases4010014
Received: 29 December 2015 / Revised: 25 February 2016 / Accepted: 7 March 2016 / Published: 10 March 2016
Cited by 3 | PDF Full-text (1623 KB) | HTML Full-text | XML Full-text
Abstract
Metabolic flexibility is the capacity of an organism to adequately respond to changes in the environment, such as nutritional input, energetic demand, etc. An important player in the capacity of adaptation through different stages of metabolic demands is the mitochondrion. In this context,
[...] Read more.
Metabolic flexibility is the capacity of an organism to adequately respond to changes in the environment, such as nutritional input, energetic demand, etc. An important player in the capacity of adaptation through different stages of metabolic demands is the mitochondrion. In this context, mitochondrial dysfunction has been attributed to be the onset and center of many chronic diseases, which are denoted by an inability to adapt fuel preferences and induce mitochondrial morphological changes to respond to metabolic demands, such as mitochondrial number, structure and function. Several nutritional interventions have shown the capacity to induce changes in mitochondrial biogenesis/degradation, oxidative phosphorylation efficiency, mitochondrial membrane composition, electron transfer chain capacity, etc., in metabolic inflexibility states that may open new target options and mechanisms of action of bioactive compounds for the treatment of metabolic diseases. This review is focused in three well-recognized food bioactive compounds that modulate insulin sensitivity, polyphenols, ω-3 fatty acids and dietary fiber, by several mechanism of action, like caloric restriction properties and inflammatory environment modulation, both closely related to mitochondrial function and dynamics. Full article
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Open AccessReview Uric Acid for Cardiovascular Risk: Dr. Jekyll or Mr. Hide?
Diseases 2016, 4(1), 12; doi:10.3390/diseases4010012
Received: 22 December 2015 / Revised: 18 February 2016 / Accepted: 19 February 2016 / Published: 26 February 2016
Cited by 3 | PDF Full-text (494 KB) | HTML Full-text | XML Full-text
Abstract
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this
[...] Read more.
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this biomarker behaves like other antioxidants, which can shift from the physiological antioxidant action to a pro-oxidizing effect according to their level and to microenvironment conditions. However, data on patients (general population or CAD cohorts) are controversial, so the debate on the role of hyperuricemia as a causative factor for CVD is still ongoing. Increasing evidence indicates UA as more meaningful to assess CVD in women, even though this aspect needs deeper investigation. It will be important to identify thresholds responsible for UA “biological shift” from protective to harmful effects in different pathological conditions, and according to possible gender-related differences. In any case, UA is a low-tech and inexpensive biomarker, generally performed at patient’s hospitalization and, therefore, easily accessible information for clinicians. For these reasons, UA might represent a useful additive tool as much as a CV risk marker. Thus, in view of available evidence, progressive UA elevation with levels higher than 6 mg/dL could be considered an “alarm” for increased CV risk. Full article
Open AccessFeature PaperReview Antioxidants and Cardiovascular Risk Factors
Diseases 2016, 4(1), 11; doi:10.3390/diseases4010011
Received: 15 December 2015 / Revised: 3 February 2016 / Accepted: 5 February 2016 / Published: 17 February 2016
Cited by 1 | PDF Full-text (204 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease (CVD), the world’s primary cause of death and disability, represents a global health problem and involves a great public financial commitment in terms of both inability to work and pharmaceutical costs. CVD is characterized by a cluster of disorders, associated with
[...] Read more.
Cardiovascular disease (CVD), the world’s primary cause of death and disability, represents a global health problem and involves a great public financial commitment in terms of both inability to work and pharmaceutical costs. CVD is characterized by a cluster of disorders, associated with complex interactions between multiple risk factors. The early identification of high cardiovascular risk subjects is one of the main targets of primary prevention in order to reduce the adverse impact of modifiable factors, from lifestyle changes to pharmacological treatments. The cardioprotective effect of food antioxidants is well known. Indeed, a diet rich in fruits and vegetables results in an increase in serum antioxidant capacity and a decrease in oxidative stress. In contrast, studies on antioxidant supplementation, even those that are numerically significant, have revealed no clear benefit in prevention and therapy of CVD. Both short- and long-term clinical trials have failed to consistently support cardioprotective effects of supplemental antioxidant intake. The aim of this review is to evaluate the antioxidant effects on the main cardiovascular risk factors including hypertension, dyslipidemia, diabetes. Full article
Open AccessReview Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer
Diseases 2016, 4(1), 6; doi:10.3390/diseases4010006
Received: 27 November 2015 / Revised: 14 January 2016 / Accepted: 15 January 2016 / Published: 22 January 2016
Cited by 3 | PDF Full-text (694 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to
[...] Read more.
Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated. Full article
Open AccessArticle Phytoconstituents with Radical Scavenging and Cytotoxic Activities from Diospyros shimbaensis
Diseases 2016, 4(1), 3; doi:10.3390/diseases4010003
Received: 10 December 2015 / Revised: 30 December 2015 / Accepted: 30 December 2015 / Published: 15 January 2016
Cited by 1 | PDF Full-text (966 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As part of our search for natural products having antioxidant and anticancer properties, the phytochemical investigation of Diospyros shimbaensis (Ebenaceae), a plant belonging to a genus widely used in East African traditional medicine, was carried out. From its stem and root barks the
[...] Read more.
As part of our search for natural products having antioxidant and anticancer properties, the phytochemical investigation of Diospyros shimbaensis (Ebenaceae), a plant belonging to a genus widely used in East African traditional medicine, was carried out. From its stem and root barks the new naphthoquinone 8,8′-oxo-biplumbagin (1) was isolated along with the known tetralones trans-isoshinanolone (2) and cis-isoshinanolone (3), and the naphthoquinones plumbagin (4) and 3,3′-biplumbagin (5). Compounds 2, 4, and 5 showed cytotoxicity (IC50 520–82.1 μM) against MDA-MB-231 breast cancer cells. Moderate to low cytotoxicity was observed for the hexane, dichloromethane, and methanol extracts of the root bark (IC50 16.1, 29.7 and > 100 μg/mL, respectively), and for the methanol extract of the stem bark (IC50 59.6 μg/mL). The radical scavenging activity of the isolated constituents (15) was evaluated on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The applicability of the crude extracts and of the isolated constituents for controlling degenerative diseases is discussed. Full article

2015

Jump to: 2017, 2016

Open AccessReview Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?
Diseases 2015, 3(3), 193-204; doi:10.3390/diseases3030193
Received: 7 July 2015 / Accepted: 21 August 2015 / Published: 2 September 2015
Cited by 4 | PDF Full-text (731 KB) | HTML Full-text | XML Full-text
Abstract
Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be
[...] Read more.
Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management. Full article

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Comprehensive Review
Title
: The role of glucosinolates and their hydrolysis products from Brassica vegetable consumption in inducing antioxidant activity and reduction of cancer incidence
Authors:
Talon M.Becker and John A. Juvik
Affiliations:
Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801-3838, IL, United States
Abstract:
The bioactivity of glucosinolates (GSs), and more specifically their hydrolysis products (GSHPs), has been well documented.These secondary metabolites evolved in the order Brassicales as plant defense compounds with proven ability to deter or impede the growth the several biotic factors including insects, fungi , bacteria, and even other plants.  However, the bioactivity of GSs is not limited to these kingdoms of life.  Many of these compounds have been shown to have bioactivity in mammalian systems as well, with epidemiological links to cancer chemoprevention in humans supported by in vitro, in vivo, and small clinical studies. The primary mechanism that is believed to be responsible for the observed chemoprevention is the induction of antioxidant enzymes, such as NAD(P)H quinone reductase (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL), and glutathione S transferases (GSTs), through the Keap1-Nrf2-ARE signalling pathway. Induction of this pathway is generally associated with aliphatic isothiocyanate GSHPs.

Type of Paper: Review
Title: Protective effect of antioxidants consumption on diabetes and vascular complications
Authors: Stéphanie DAL and Séverine SIGRSIT
Affiliation: Centre Européen d’Etude du Diabète, boulevard René Leriche, 67200 Strasbourg, France
Abstract: Today, WHO draws attention to the similarity of trends in obesity and diabetes in the World. The term “diabesity” is commonly used today to describe this epidemic or pandemic with exponential dramatic growth observed in all countries. Our change of lifestyle to a sedentary attitude and massive industrialization with access from an early age to food and beverages rich in energy, fat and/or sugar, would be partly the cause of millions of obese and diabetic people. Despite the range of tools available to fight against the disease - effective medications, advanced technology, and education strategies continuously improved prevention - we are losing the fight to protect people from diabetes and its disabling complications and potentially fatal. In fact, diabetes is a silent disease and sneaky. Therefore, it is associated with many complications. Cardiovascular diseases are the first cause of death and disability among diabetic people, particularly for woman who lost cardiovascular protection afforded by the classically female sex. Diabetic vascular complications are an important pathological issue in diabetes that leads to the further functional deterioration of several organs and caused micro- and macro-angiopathy. Endothelial dysfunction, the loss of a balance between vasodilators and vasoconstrictors factors in the blood vessels, has largely been associated in several regions of the vasculature in T2D.
One of the common points to all these cardio-metabolic disorders is the appearance of oxidative stress. Oxidative stress is due to an imbalance between antioxidants (enzymes, vitamins, proteins) and pro-oxidants (UV radiations, alcohol, smoking…). Oxidative stress along with chronic lowgrade inflammation may initiate changes in cardiovascular structure and function such as endothelial dysfunction, cardiac hypertrophy, cardiac fibrosis, and ventricular contractile dysfunction. Many studies have shown that diabetic patients undergoing chronic oxidative stress, particularly due to hyperglycemia. Thus, a strategy focus on both, oxidative stress and endothelial function, could help to prevent and / or delay the onset of vascular-related type 2 diabetes complications.
Much evidence shows that consumption of natural source substances confers chemopreventive and cytoprotectant activities. In fact, epidemiological studies suggest that consumption of fruits, vegetables and plants may be associated with a reduced risk of diabetes or a protective effect. In fact, strongest evidence exists for a beneficial effect of cocoa on endothelial function and insulin sensitivity or green tea on LDL-cholesterol even if long-term randomized trials need to confirm these. Green leafy vegetables (spinaches), dark yellow vegetables (carrots) or citrus fruit are some fruit and vegetables inversely associated with diabetes. Their consumption brings several exogenous antioxidants and vitamins, increasing the antioxidant status of the organism. Same observations have also revealed an inverse relationship between the risk of cardiovascular mortality and morbidity and the consumption of polyphenol-rich products (red wine, cacao and tea) attributable at least in part to their direct effect on blood vessels and in particular on the endothelium.
Many plants are also used for their benefits in traditional medicines. Some of them are at the origin of the development of drugs such as biguanide metformin, antidiabetic drug, through Galega officinalis. In developed countries, traditional, complementary and alternative medicines are becoming increasingly popular and they are commonly used to treat or prevent chronic diseases and improving the quality of life.
So, we will see through this review that many compounds surrounding us can be a real asset in the prevention of ‘diabesity’ but also a valuable aid in addition to current treatments to prevent the occurrence of such complications. We will also discuss the appeal for the use of single molecules to the detriment of total extracts thereby promoting molecular synergy. Finally, we will complete the rise of food supplements that are increasingly important in our daily lives.

Type of Paper: Review
Title: Food Bioactives in Prevention of Cardiovascular Diseases and Human Cancers
Authors: Nagisa Nosrati, Marica Bakovic, Gopinadhan Paliyath
Affiliations: -Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, N1G 2W1,Canada
-Department of Plant Agriculture, University of Guelph, Guelph, ON, N1G 2W1, Canada
Abstract: Nutraceuticals are bioactive ingredients in functional foods. A common feature of several functional ingredients is their antioxidant function. Plant based food materials have higher levels of antioxidants than animal based foods. Antioxidants with a wide range of chemical structure and function provide different health benefits beyond basic nutrition helping the prevention of chronic diseases. Functional food ingredients modulate the signal transduction and gene expression increasing the antioxidant status in addition to their ability to scavenge ROS, and detoxifying reactive oxygen and nitrogen species, capable of protecting and repairing DNA damage. A major pathway that is affected by functional food ingredients is the anti-inflammatory pathway, via down-regulation of NF-κB and pro-inflammatory cytokines. Through their antioxidant function bioactive compounds can reduce cardiovascular disease risk factors, such as cholesterol, LDL, triglycerides and oxidized LDL. The role and mechanisms of nutrigenetics, nutrigenomics and epigenomics on cardiovascular disease development is poorly understood. The present review summarizes the importance of nutrients and their role in gene expression, and how epigenetic changes and micro RNAs (miRNAs) can alter cellular signaling in response to nutrients that may help prevent the development of cardiovascular diseases or Cancers.

Title: Polyphenols of Grapevine as Chemopreventive Agents to Counteract Carcinogenesis
Authors: Pauline Chalons 1,2 Laetitia Nivelle 3 Flavie Courtaut 1,2 Emeric Limagne 1,2 Michel Tarpin 3 Laurent Martiny 3 Antonio Leon-Gonzalez 4 Valérie Schini-Kerth 4 Virginie Aires 1,2 and Dominique Delmas 1,2
Affiliations: 1 University of Burgundy, Dijon, F-21000, France
2 Inserm Research Center U866 – Chemotherapy, Lipid Metabolism and Antitumoral Immune Response Team, Dijon, F-21000, France
3 Université de Reims Champagne Ardenne, UMR CNRS/URCA 7369 MEDyC, Laboratoire SiRMa UFR SEN, Moulin de la Housse, BP 1037, 51687 Reims Cedex, France
4 Université de Strasbourg, UMR CNRS 7213 - Biophotonique et Pharmacologie, Faculté de Pharmacie, 67401 Illkirch, France
Abstract: A wide variety of plant-derived compounds, including polyphenols and flavonoids, is present in the human diet and may protect against vascular diseases, cancers and associated inflammatory effects. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that showed protective effects of plant-based diets on cardiovascular diseases and cancers. Among these compounds, polyphenols produced by grapevine seem to be good candidates for chemoprevention against various degenerative diseases. In this review, we focus on the potential protective effects of red wine extract and polyphenols content in carcinogenesis and more particularly in intestinal cancer. The different signaling pathways contributing to tumor development and progression, including reactive oxygen species and cytokine production, cell cycle regulation, apoptosis, were analyzed in relation with the different polyphenol found in grapevine. Especially, we highlight that some polyphenols have synergistic effect to counteract tumor development and, at the inverse, some polyphenols have an antagonist action. Furthermore, isolation and used of pure polyphenol alone or in combination with therapeutically drugs could constitute a potential tools for new therapeutic strategies against cancer by acting on various therapeutic cellular targets.

Type of Paper: Short communication or research paper
Tentative Title: Coffee Reduces KRAS Expreesion in Human Colon Carcinoma, Caco-2 Cells
Authors: Takuya Nakayama and Hiroomi Tamura
Affiliation: School of Pharmaceutical Sciences, Keio University, Tokyo, Japan
Abstract: Recent epidemiological studies have shown that a moderate coffee consumption is associated with a lower risk of certain types of cancers, particularly colon cancer. To elucidate the molecular basis for the preventive action of coffee, we investigated the effect of coffee on Caco-2 cells. Low concentration coffee (<5%) inhibited proliferation of Caco-2 cells without affecting cell viability. We found that coffee reduced KRAS gene expression in a coffee-dose dependent manner. Analysis of miRNAs revealed that coffee induced the expression of miR-30c and miR-96 genes both of which target KRAS gene. Major constituents such as caffeine, caffeic acid, chlorogenic acid and trigonelline did not exhibit such effect. Increasing roasting degree of coffee beans enhanced the reduction in KRAS expression suggested that the active components emerge during roasting process. Our data suggest that daily coffee consumption may reduce the KRAS activity and thereby prevent malignant growth of colon cells.

Type of the paper: Review
Tentative title:
Chemopreventive Properties of Ellagic Acid and Its Derivatives
Authors:
Andrade, JC1 and Silva FAM1,2
Affiliations:
1 CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
2
CIQ-UP, Centro de Investigação em Química da Universidade do Porto, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal
Abstract:
Chemoprevention/treatment through the use of naturally occurring phytochemicals has been considered a valuable approach for cancer management. Ellagic acid (EA) is a dietary polyphenol that attracted much attention in recent years due to its multiple biological activities including antioxidant, anti-inflammatory and anti-tumorigenic. EA occurs, mainly in the form of ellagitannins (ETs), in strawberries, raspberries, blackberries, pomegranates, walnuts and oak-aged wines. Under physiological conditions, ETs are hydrolyzed to EA which is metabolized by the intestinal microbiota to produce different types of urolithins. This review presents a comprehensive outlook for the potential chemopreventive properties of EA and ETs and their derivate metabolites.

Type of the paper: Review
Tentative title: The cardiovascular effects of cocoa polyphenols-an overview
Authors: Aprotosoaie Ana Clara 1, Anca Miron 1, Adriana Trifan 1, Vlad Simon Luca 1, Irina Iuliana Costache 2
Affiliations: 1 Department of Pharmacognosy, Faculty of Pharmacy, University of Medicine and Pharmacy Grigore T.Popa-Iasi, Iasi, Romania; 2 Department of Cardiology, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa-Iasi, Iasi, Romania; “Sf. Spiridon” University Hospital Iasi, Romania
Abstract: Cocoa is a rich source of high quality antioxidant polyphenols. They comprise mainly catechins (29-38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%-65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function. This paper reviews the role of cocoa polyphenols in cardiovascular protection, with a special focus on mechanisms of action, clinical relevance and correlation between antioxidant activity and cardiovascular health.

Type of the paper: Review
Title: Dietary antioxidants and cancer risk factors: functions and structural insights
Authors: Khaled A. Selim 1, Ahmed Tawila 2, Mohamed Aboel-Magd 3 and Hend Abdel-Rasoul 4
Affiliations: 1 Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls Universität Tübingn, Germany; 2 Pharmacognosy Department, Pharmaceutical and drug industries research division, National Research Centre; 3 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, USA; 4 Institute of Immunology, Ulm University, Germany
Abstract: Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and generated in response to several environmental stress conditions. Some of them are playing important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses. The oxidative stress of redundant free radicals production can lead to oxidative denaturation of cellular macromolecules including proteins, lipids and DNA. Moreover, the oxidative damage is one of major causes of DNA mutations, replication errors and genomic abnormalities result in either inhibition or induction of transcription, ended with disturbance of signal transduction pathways. Among affected signaling pathways are redox-sensitive kinases. The stimulation of these kinases induces several transcription factors through the phosphorylation of their module proteins. The activation of such pathways induces proliferation and cellular transformation. Diet rich in antioxidant compounds have potential health benefits, and there is a growing interest on the role of natural antioxidants in nutrition for prevention and cure of cancer diseases. In term of mechanisms of action, the naturally antioxidant agents can be classified into enzymatic and non- enzymatic antioxidants. The first type can act by stimulation of antioxidant enzyme systems (GSH reductase, superoxide dismutase and catalase), while the non-enzymatic antioxidants exert their action through inhibition of free radical formation, free radical scavenging activity and direct reducing power. These activities can be attributed to the vast accumulation of antioxidant components present in natural products including polyphenolics, flavonoids, isoprenoids, vitamins and minerals. A controversy has risen regarding the relation between antioxidants and the significant decrease in the risk of cancer incidence. In this review, we will focus on redox-sensitive kinases signaling pathways, with highlighting the effects of dietary antioxidant on the prevention, incidence, prognosis or even treatment of human cancers. Besides, we will emphasis on the chemical classes of food antioxidants as well as their underlying mechanisms of action.

Tentative Title: The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases.
Authors: Robert E. Smith 1, Kevin Tran 1, Cynthia Smith 1, Miranda McDonald 1, Pushkar Shejwalkar 2, Kenji Hara 2
Affiliations: 1 FDA, Lenexa, KS 66214, USA; 2 Tokyo University of Technology, Tokyo, Japan
Abstract: The circulatory system was once thought to be like plumbing in a well-regulated machine. Cardiovascular diseases were thought to be caused when one’s arteries became clogged with cholesterol. However, it is now widely accepted that smoldering inflammation caused by reactive oxygen species (ROS) occurs first. For a long time, it was thought that dietary antioxidants could help prevent cardiovascular diseases by reacting with ROS and destroying them directly. Several fruits became known as super foods, since they contained relatively high concentrations of antioxidants. The U.S. Department of Agriculture even maintained a website that listed the total *in vitro* antioxidant potentials of many foods and spices. However, the website was taken down after it became apparent that consuming large quantities of dietary antioxidants had no apparent therapeutic value. Since then, it has become apparent that not all dietary antioxidants are equal. Some, like curcumin, turmeric and epigallocatechin gallate (EGCG) activate a transcription factor, nuclear erythroid-2 like factor-2 (Nrf2), which activates antioxidant response elements (ARE). When the Nrf2/ARE signaling system is properly activated, it can help prevent smoldering inflammation and cardiovascular diseases. However, when over-activated, the Nrf2/ARE system can cause cardiovascular diseases and multidrug resistant cancers. The mechanisms behind the activation and control of the Nrf2/ARE system will be reviewed.

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