Bacterial folate biosynthesis and colorectal cancer risk: more than just a gut feeling

Abstract

Folate is a B-vitamin with an important role in health and disease. The optimal folate status with regard to human health remains controversial. A low intake of natural folate as well as excessive intake of synthetic folic acid, were previously linked to an increased risk of colorectal cancer or with aberrant molecular pathways related to carcinogenesis in some studies. Importantly, most studies conducted so far, solely focused on dietary intake or circulating levels of folate in relation to cancer risk. Notably, diet or dietary supplements are not the only sources of folate. Several bacteria in the gastrointestinal tract can synthesize B-vitamins, including folate, in quantities that resemble dietary intake. The impact of bacterial folate biosynthesis concerning human health and disease remains unexplored. This review highlights current insights into folate biosynthesis by intestinal bacteria and its implications for processes relevant to cancer development, such as epigenetic DNA modifications and DNA synthesis. Moreover, we will reflect on the emerging question whether food-grade or intestinal bacteria can be considered a potential target to ensure sufficient levels of folate in the gastrointestinal tract and, hence the relevance of bacterial folate biosynthesis for disease prevention or treatment.     

Management of hyperuricemia through dietary polyphenols as a natural medicament: A comprehensive review

Hyperuricemia, a condition due to high serum uric acid level and is notorious to health. It is considered to be a potent risk factor for gout and dramatically associated in the development of many chronic diseases such as malignant tumor, cardiovascular disorders and renal failure. Modern innovative medicinal and therapeutic interventions are underlying these days to combat hyperuricemia. Previously reported studies revealed the significant impact of dietary polyphenols (e.g. anthocyanins, phenolic acids, flavonoids etc.) against hyperurecemia disorder. Dietary plant polyphenols, unlike anti- hyperuricemic agents, are not reported to have any side effects in curing hyperuricemia. The current comprehensive review figure outs the use of dietary polyphenols as a natural remedy for the management of hyperuricemia. The sources, affiliated pathways, mode of actions and factors affecting their efficiency to prevent hyperuricemia are deeply discussed in this article. Additionally, limitations and suggestions regarding previously reported studies are also highlighted.     

A critical review of the relationship between dietary components,the gut microbe Akkermansia muciniphila,and human health

Abstract

The human gut contains trillions of microorganisms with a great diversity that are associated with various health benefits. Recent studies have reported an increasing correlation between diet, gut microbiota, and human health, indicating rapid development in the field of gut health. Diet is an important factor that determines the gut microbiota composition. The gut comprises great diversities of microbes involved in immune modulation and other functions. In particular, Akkermansia muciniphila is a mucin-degrading bacterium is believed to have several health benefits in humans. Several studies have evaluated the prebiotic effects of various dietary components on A. muciniphila and their association with various ailments, such as diabetes mellitus, atherosclerosis, and cancer. Hence, this review aims to provide a plausible mechanistic basis for the interactions between dietary components, and A. muciniphila and for the therapeutic benefits of this interaction on various illnesses.     

Immunity: Plants as Effective Mediators

In the domain of nutrition, exploring the diet–health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.     

Dietary fibre and colorectal cancer: a model for environment--gene interactions

As environmental factors are clearly associated with risk for colorectal cancer, we set out to model how dietary fibre, or the effects of its ingestion, might impact upon the complex events that characterise colorectal oncogenesis. The diverse nature of dietary fibre and its resultant fate in the gut is outlined. The evidence indicates that different types of fibre create different conditions in different regions of the gut. This is reflected in different effects on oncogenesis especially in animal models. Data from animal models show that insoluble fibre is protective. Evidence from human studies are not consistent, especially considering the interventional studies. However, all such studies have been dependent on biomarkers short of cancer formation, for measurement of an effect. The biological and molecular events characteristic of colorectal oncogenesis are reviewed in an effort to identify how fibre ingestion might regulate oncogenesis. While several mechanisms might account for protection, the results of fermentation and especially butyrate production provide examples of how genomic instability might be controlled. Activation of apoptosis and cell cycle arrest seem likely to be mechanisms that would enable correction of genomic events that drive oncogenesis. Butyrate itself can regulate gene expression by both epigenetic and direct effects.     

Dietary phenolics against colorectal cancer—From promising preclinical results to poor translation into clinical trials: Pitfalls and future needs

Colorectal cancer (CRC) remains a major cause of cancer death worldwide. Over 70% of CRC cases are sporadic and related to lifestyle. Epidemiological studies inversely correlate CRC incidence with the intake of fruits and vegetables but not with their phenolic content. Preclinical studies using in vitro (cell lines) and animal models of CRC have reported anticancer effects for dietary phenolics through the regulation of different markers and signaling pathways. Herein, we review and contrast the evidence between preclinical studies and clinical trials (patients with CRC or at risk, familial adenopolyposis or aberrant crypt foci) investigating the protective effects of curcumin, resveratrol, isoflavones, green tea extracts (epigallocatechin gallate), black raspberry powder (anthocyanins and ellagitannins), bilberry extract (anthocyanins), ginger extracts (gingerol derivatives), and pomegranate extracts (ellagitannins and ellagic acid). To date, curcumin is the most promising polyphenol as possible future adjuvant in CRC management. Overall, the clinical evidence of dietary phenolics against CRC is still weak and the amounts needed to exert some effects largely exceed common dietary doses. We discuss here the possible reasons behind the gap between preclinical and clinical research (inconsistence of results, lack of clinical endpoints, etc.), and provide an outlook and a roadmap to approach this topic.     

Impact of plant extracts upon human health: A review

Abstract

With the increase in evidences directly linking diet and health, several foodstuffs, such as phenolic rich fruits and vegetables, have emerged as possessing potential health benefits. Plants, given their fiber and phenolic content (and their intrinsic biological potential), have long been considered as contributing to health promotion. Therefore, the present work aimed to review the existing evidences regarding the various potential benefits of plant extracts’ and plant extract-based products’ consumption, with emphasis on in vivo works and epidemiological studies whenever available. Overall, the information available supports that, while there are indications of the potential benefits of plant extracts’ consumption, further human-based studies are still needed to establish a true cause-effect.     

The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

Current focus in colorectal cancer (CRC) management is on reducing overall mortality by increasing the number of early-stage cancers diagnosed and treated with curative intent. Despite the success of screening programs in down-staging CRC, interval cancer rates are substantial and other strategies are desirable. Sporadic CRC is largely associated with lifestyle factors including diet. Polyphenols are phytochemicals ingested as part of a normal diet, which are abundant in plant foods including fruits/berries and vegetables. These may exert their anti-carcinogenic effects via the modulation of inflammatory pathways. Key signal transduction pathways are fundamental to the association of inflammation and disease progression including those mediated by NF-κB and STAT, PI3K and COX. Our aim was to examine the evidence for the effect of dietary polyphenols intake on tumor and host inflammatory responses to determine if polyphenols may be effective as part of a dietary intervention. There is good epidemiological evidence of a reduction in CRC risk from case-control and cohort studies assessing polyphenol intake. It would be premature to suggest a major public health intervention to promote their consumption; however, dietary change is safe and feasible, emphasizing the need for further investigation of polyphenols and CRC risk.     

Dietary plant materials reduce acrylamide formation in cookie and starch-based model systems

BACKGROUND: Dietary plant materials have attracted much attention because of their health benefits to humans. Acrylamide is found in various heated carbohydrate‐rich foods. Our previous results showed that crude aqueous extracts from diverse dietary plants and some phenolic compounds could mitigate acrylamide formation in an asparagine–glucose model system. Based on our previous study, several plant materials were selected to further investigate their inhibitory effects on acrylamide formation in cookies and starch‐based model systems. RESULTS: Addition of raw powders from selected dietary plants and their crude aqueous extracts could considerably reduce acrylamide formation in both cookie and potato starch‐based models. Aqueous extracts of clove at 4% caused the largest reduction (50.9%) of acrylamide in cookies, whereas addition of 2% proanthocyanidins from grape seeds gave the greatest acrylamide reduction (62.2%) in a starch‐based model system. CONCLUSION: It may be feasible to use some of the tested dietary plant materials to reduce acrylamide formation in cookies and other starchy foods. Copyright © 2011 Society of Chemical Industry     

Anti-inflammatory properties of hydroalcoholic extracts of Argentine Puna plants

The aim of this study is to evaluate the activity of thirteen hydroalcoholic extracts obtained from aerial parts of plants from the Argentine Puna on pro-inflammatory enzymes and inflammatory mediators.Eleven extracts were non-cytotoxic on RAW 264.7. Data obtained suggest the capacity of these Argentine Puna plant extracts to inhibit the production of inflammatory mediators (nitric oxide and prostaglandin) at different levels. The plant extracts can affect enzyme expression and/or enzyme activity, and they can also act by NO scavenging. Each extract exerts its anti-inflammatory effect through different mechanisms. The inhibitory ability on pro-inflammatory enzymes by these hydroalcoholic extracts supports their potential use as sources of natural anti-inflammatory agents. Moreover, all extracts were non-toxic on Artemia salina toxicity test. The consumption of dietary supplements prepared with these plant species could be used to prevent the development of chronic inflammatory pathologies.     

Determination of herb authenticity by low-field NMR

The safe use of herbal medicines requires prior authentication of the raw materials used to make them. This is an important step, since the ingestion of herbal preparations or extracts can cause serious health problems. Among the different analytical techniques, nuclear magnetic resonance (NMR) spectroscopy has the advantage of being non-invasive and therefore suitable for the characterization of natural products such as medicinal plants. This work presents a characterisation study of the samples of the popular plant Maytenus ilicifolia, obtained from different commercial producers. This plant is used for the treatment of gastrointestinal disorders, as it possesses antitumorigenic, analgesic, anti-inflammatory and antioxidant properties. The differences in the chemical structure and molecular organisation detected by thermogravimetric analysis (TGA), infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) were also investigated by proton nuclear magnetic resonance relaxometry, in particular by fast field cycling (FFC) relaxometry, and relaxometry in the rotating frame. All results confirmed the similarity between the control sample and only one of the plant investigated. The differences detected between the samples could be related to their non-authenticity, due to the non recognise the plant due to the leaves similarity among plants from the same family and/or contamination, due to addition of similar other plants parts to the commercial ones, as they are mixed together this difficulties the acceptation of the plant.     

Are the proposed benefits of melatonin-rich foods too hard to swallow?

Melatonin has been proposed as a potent anti-oxidant, and its presence in many plants and foods has been suggested to be beneficial for health. Indeed, the concentrations of melatonin in blood and the melatonin metabolite 6 sulphatoxymelatonin in urine have been found to increase significantly after ingestion of melatonin-rich foods. In this review, the studies have been critically evaluated in light of the reported plant melatonin concentrations and our knowledge of pharmacokinetics of orally administered pure melatonin. In the case of studies involving measurement of plasma melatonin following ingestion of beer or fruits, the reported increase in melatonin is not consistent with the amount of melatonin ingested. Similarly, the amount of melatonin metabolite excreted following ingestion of melatonin-rich foods greatly exceeded the amount of melatonin ingested. It is concluded that studies reporting the appearance of melatonin in blood and its metabolites in urine following ingestion of melatonin-rich foods are flawed. While there may be health benefits for certain foods, it is difficult to accept that these are due to their low melatonin content.     

Dietary nutrition and gut microflora: A promising target for treating diseases

BackgroundThe human gastrointestinal tract harbors hundreds of millions of microorganisms, which create a unique environment for each individual. The relationship between gut microflora and human health is being increasingly recognized, and the influence of gut microbiota on the host is well characterized, including maintenance of the body's energy metabolism and immune system. Gut microbiota have been found to be closely linked to obesity, allergy, diabetes, cancer or even some mental diseases. Diet can strongly affect human health, partly by modulating gut microbial composition and quantity.Scope and ApproachIn this review, the relationship between diseases and gut microbes and the effect of different dietary components on gut microflora are summarized. This paper mainly focused on how different diet structure such as high intake of dietary fiber, fat, protein and alcohol etc. may exert impact on specific diseases via gut microflora.Key findings and conclusionsSpecific diseases can be strongly affected by gut microflora and dietary nutrition plays an important role in affecting the composition of gut microflora for individuals since their birth. A bridge between diets and multiple diseases via gut microbiota is built in this review, hopefully to provide references for further investigation of how the diets affect human health via gut microflora and for development of functional foods targeting on gut microflora to solve some health problems.     

Chemoprevention: Insights into biological mechanisms and promising food factors

Abstract

Chemoprevention with food phytochemical is currently regarded as one of the noticeable scientific fields. A large body of data from epidemio‐logic and rodent studies has demonstrated that ingestion of vegetables and fruits is occasionally beneficial for reduction of cancer risks in humans. Recent clinical trials using ubiquitous antioxidants such as α‐carotene, however, have yet to show their cancer preventive effect despite the fact that they have been reported to be chemopreventive agents in rodent models. One of the goals of this review is to address useful and reliable methodology to detect promising chemopreventive agents from edible plants by highlighting molecular mechanisms of multistage carcinogenesis.     

Mass spectrometry-based approaches to assess the botanical authenticity of dietary supplements

Dietary supplements are legally considered foods despite frequently including medicinal plants as ingredients. Currently, the consumption of herbal dietary supplements, also known as plant food supplements (PFS), is increasing worldwide and some raw botanicals, highly demanded due to their popularity, extensive use, and/or well-established pharmacological effects, have been attaining high prices in the international markets. Therefore, botanical adulteration for profit increase can occur along the whole PFS industry chain, from raw botanicals to plant extracts, until final PFS. Besides the substitution of high-value species, unintentional mislabeling can happen in morphologically similar species. Both cases represent a health risk for consumers, prompting the development of numerous works to access botanical adulterations in PFS. Among different approaches proposed for this purpose, mass spectrometry (MS)-based techniques have often been reported as the most promising, particularly when hyphenated with chromatographic techniques. Thus, this review aims at describing an overview of the developments in this field, focusing on the applications of MS-based techniques to targeted and untargeted analysis to detect botanical adulterations in plant materials, extracts, and PFS.     

Functional Foods: Their Role in Health Promotion and Disease Prevention

ABSTRACT: The effect of food factors on health status has been recognized since antiquity. More recently, epide-miological studies have led to fundamental research for unraveling the chemistry and mechanism of action of dietary phytochemicals and bioactives. Functional foods and natural health products encompass a wide range of food and ingredients, with a variety of bioactives responsible for their efficacy in health promotion and disease prevention. Phenolic and polyphenolic compounds constitute an important class of secondary plant metabolites that act as free radical scavengers and inhibitors of LDL cholesterol oxidation and DNA breakage, among others. Thus, the role of food phenolics and polyphenolics in the prevention of cardiovascular disease and certain types of cancer is well recognized. In addition, certain marine foods have often been considered as "heart food" because of their omega-3 constituents which are known to lower blood triacylglycerol and, possibly, cholesterol levels. Thus, food factors from both plants and animals may be participating in human health promotion.     

Chemopreventive functions of sulforaphane: A potent inducer of antioxidant enzymes and apoptosis

Epidemiological and dietary studies have revealed an association between high intake of cruciferous vegetables and decreased cancer risk cancer. Sulforaphane, a phytochemical constituent of cruciferous vegetables, has received much attention as a potential cancer chemopreventive compound. Recent advances in the cellular and molecular biology of cancer have shed light on components of intracellular signaling cascades that can be molecular targets of chemoprevention by various anti-cancer agents. Metallothionein (MT), a primary antioxidant enzyme involved in the metabolism and detoxification of heavy metal, has been recognized as a molecular target for chemoprevention by natural anti-cancer agents, but the cellular signaling mechanisms that associate MT gene regulation are not yet clearly understood. Recent studies suggest that Nrf2-mediated signaling, which controls the expression of many of genes responsible for carcinogen detoxification and protection against oxidative stress, is regulated by sulforaphane. This contribution focuses on Nrf2-mediated signaling pathways, particularly in relation to MT gene induction and the apoptosis-inducing effects of sulforaphane.     

Benzoxazinoids: Cereal phytochemicals with putative therapeutic and health‐protecting properties

Benzoxazinoids (BXs) are a group of natural chemical compounds with putative pharmacological and health‐protecting properties. BXs were formerly identified in and isolated from selected dicot medicinal plants and young cereal plants. Recently, BXs were found to be present in mature cereal grains and bakery products, such that knowledge about the pharmacological properties of BXs, which until now have unknowingly been consumed through the daily bread and breakfast cereals, has come into new focus. This review discusses published results from in vitro studies and a few human and animal model studies on the health effects and pharmacological responses of various BX compounds. Many of these studies have reported antimicrobial, anticancer, reproductive system stimulatory, central nervous system stimulatory, immunoregulatory, and appetite‐ and weight‐reducing effects of BXs and/or BX derivatives. The health benefits of wholegrain intake may be associated with the solitary and/or overlapping biological effects of fibers, lignans, phenolic acids, alkylresorcinols, BXs, and other bioactive compounds. In the context of BXs as dietary ingredients, further comprehensive investigations are required to understand their biological functions, to elucidate the underlying mechanisms, to explore their potential contribution on the health effects associated with wholegrain consumption, and to examine their potential as functional food ingredients.     

Chemistry,natural sources,dietary intake and pharmacokinetic properties of ferulic acid: A review

Ferulic acid (FA) is an abundant dietary antioxidant which may offer beneficial effects against cancer, cardiovascular disease, diabetes and Alzheimer’s disease. The impact of FA on health depends on its intake and pharmacokinetic properties. In this article, the literature pertaining to chemistry, natural sources, dietary intake and pharmacokinetic properties of FA is critically reviewed. High levels of FA are found in both free and bound forms in vegetables, fruits, cereals, and coffee. We have estimated that consumption of these foods may result in approximately 150–250 mg/day of FA intake. FA can be absorbed along the entire gastrointestinal tract and metabolized mainly by the liver. The absorption and metabolism of FA seem to be dose dependent at least in experimental settings. Further pharmacokinetic and pharmacodynamic studies are required to characterize the impact of FA on human health.