Current Pharmaceutical Design - Volume 23, Issue 19, 2017

Background: Glucosinolates (GLSs) are dietary plant secondary metabolites occurring in the order Brassicales with potential health effects, in particular as anti-carcinogenic compounds. GLSs are converted into a variety of breakdown products (BPs) upon plant tissue damage and by the gut microbiota. GLS biological activity is related to BPs rather than to GLSs themselves. Methods: we have reviewed the most recent scientific literature on the metabolic fate and the biological effect of GLSs with particular emphasis on the epidemiological evidence for health effect and evidence from clinical trials. An overview of potential molecular mechanisms underlying GLS biological effect is provided. The potential toxic or anti-nutritional effect has also been discussed. Results: Epidemiological and human in vivo evidence point towards a potential anti-cancer effect for sulforaphane, indole-3-carbinol and 3,3-diindolylmethane. A number of new human clinical trials are on-going and will likely shed further light on GLS protective effect towards cancer as well as other diseases. BPs biological effect is the results of a plurality of molecular mechanisms acting simultaneously which include modulation of xenobiotic metabolism, modulation of inflammation, regulation of apoptosis, cell cycle arrest, angiogenesis and metastasis and regulation of epigenetic events. BPs have been extensively investigated for their protective effect towards cancer but in recent years the interest also includes other diseases. Conclusion: It appears that certain BPs may protect against and may even represent a therapeutic strategy against several forms of cancer. Whether this latter effect can be achieved through diet or supplements should be investigated more thoroughly.

Background: Dietary supplements have been widely used among the United States of America (USA) and the European Union (EU) population not only as a form of nutrition but also for medicinal purposes. Still, the legislation regulating these supplements remains unclear due to the fact that they can be considered as foodstuffs and/or medicinal products depending on various factors. Methods: The present review article intends to provide information concerning the variations on the definition of dietary supplements, the allowable substances on it, as well as the marketing and labelling requirements among the USA and the EU legislation. Results/Conclusions: In fact, several discrepancies can be found between regulations in the USA (mainly regulated by the Food and Drugs Administration) and in the EU (principally regulated by the Food Supplements Directive or by the Directive 2001/83/EC), and even between the different Member States of the EU, with the main differences observed in new products marketing requirements.

Background: Eating behaviours are closely related to some medical conditions potentially leading to death such as cancer, cardiovascular disease and diabetes. Healthy eating practices, maintaining a normal weight, and regular physical activity could prevent up to 80% of coronary heart disease, 90% of type-2 diabetes and onethird of all cancers [1]. Method: Over the last two decades, the food industry has invested much effort in research and development of healthier, more nutritious foods. These foods are frequently designated “functional” when they contain nutritional components required for healthy living or “nutraceuticals” when intended to treat or prevent disease or disorders through a variety of bioactive (e.g., antioxidant, antimicrobial, immunomodulatory, hypocholesterolaemic) functions that are performed by functional enzymes, probiotics, prebiotics, fibres, phytosterols, peptides, proteins, isoflavones, saponins or phytic acid, among other substances. Results: Some agricultural and industrial residues have proven to be excellent choices as raw materials for producing bioactive compounds and have been proposed as potentially safe natural sources of antimicrobials and/or antioxidants for the food industry. Functional food ingredients containing bioactive compounds could be used as plant extracts by pharmaceutical and food industries. Conclusion: Bioactive food components influence health outcomes.

Background: Interest in protein-phenol interactions in biological systems has grown substantially in recent decades. Methods: The interest has focused largely on food systems in response to reports on the prominent roles of phenolic compounds in nutrition and health. Results: Phenolic compounds can have both favourable and adverse nutritional effects. Polyphenols are widely known for their antioxidant, anti-inflammatory, anticancer and antiaging properties; however, they have also been ascribed anti-nutritional effects resulting from interactions with some proteins and enzymes. Interactions between proteins and polyphenols can additionally influence food quality by altering some physical–chemical and sensory properties of foods. These effects may be useful to develop new products in food science and technology provided the nature of physical–chemical interactions between proteins and phenols is accurately elucidated. In this paper, we review the different possible modes of interaction between selected food proteins and phenolic compounds. Conclusion: Existing knowledge on the mechanisms behind polyphenol–protein reactions, the structures of the resulting products and their potential uses is reviewed.

Background: The exact mechanism(s) of atherosclerosis in humans remains elusive, but one theory hypothesizes that this deleterious process results from the oxidative modification of low-density lipoprotein (LDL). Research suggests that foods rich in dietary phenolic compounds with antioxidant activity can mitigate the extent of LDL oxidation in vivo. With regard to the different classes of flavonoids, there appears to be a structurefunction relationship between the various moieties/constituents attached to the flavonoids' three ring system and their impact at retarding LDL oxidation. Methods: This article summarizes the findings to date of both in vitro and in vivo studies using foods or phenolic extracts isolated from foodstuffs at inhibiting the incidence of LDL oxidation. Three bases: SCOPUS, Web Science, and PubMed were used for search. Results: An often used method for the determination of antioxidant properties of natural phenolic compounds is the LDL oxidation assay. LDLs are isolated from human plasma and their oxidation is induced by Cu2+ ions or 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The sample is incubated with a phenolic extract or individual/isolated phenolic compounds. LDL oxidation is then monitored by various chemical methods (e.g., measurement of the generation of conjugated dienes and trienes). This technique confirmed the antioxidant properties of several extracts as obtained from plant material (e.g., grapes, berries, orange, grapefruit, coffee, tea, chocolate, olives, nuts) as well as the individual phenolic compounds (e.g., luteolinidin, apigenidin, caffeic acid, chlorogenic acid, catechin, quercetin, rutin). Several studies in vivo confirmed protective effects of phenolic compounds against LDL oxidation. They covered the healthy subjects with hyperlipidaemia, overweight, obesity, metabolic syndrome, heavy smokers, patients receiving haemodialysis, patients with peripheral vascular disease, and subjects at high cardiovascular risk. The studies comprise individuals of all ages, and the number of participants in the different experiments varied widely. Conclusion: Properly designed double-blind, placebo-controlled randomised clinical trials offer stronger evidence as to the impact of dietary phenolics consumption at retarding LDL oxidation. More such clinical trials are needed to strengthen the hypothesis that foods rich in dietary phenolic compounds with antioxidant activity can mitigate the extent of LDL oxidation in vivo.

Background: In recent years, a growing interest has developed in the field of biological activity of plant metabolites. Research in this area considering antimicrobial, antioxidant, cytotoxic, anti-inflammatory, and other properties, is currently expanding, reporting various species to possess such biological effects. Among them, Centaurea species are well known to be used in ethnomedicine. The Centaurea genus (Asteraceae) is represented by more than 500 species, mostly located in the Mediterranean region and Western Asia. Methods: The current revision focuses on up-to-date literature on the isolation, structural elucidation and biological properties of sesquiterepene lactones from Centaurea species, regarding antimicrobial, antitumour, antiviral, anti-inflammatory and cytotoxic properties. The methods for extraction, isolation and identification are also pointed out and the bioactivity of lactones as purified compounds discussed. Several general ideas about the structural requirements for activity, based on the in vitro bioassays and the in silico prediction of their ADME properties are discussed. Results: Investigations of chemical analyses and biological potential exhibited that flavonoids and sesquiterpene lactones, in particular germacranolides, eudesmanolides, elemanolides, and guaianolides, are compounds responsible for the biological potential of plants. Sesquiterpene lactones represent a group of compounds responsible for the medicinal characteristics of Centaurea species. Discussion: Investigation of structure-activity relationships of all data helps the understanding of the bioactivity resulting from chemical aspects. All activities are discussed profoundly, paying special attention to molecular mechanisms involved in the implication of the health-beneficial effects of these compounds and in order to point them out as candidates for new drug discovery, and as safe natural agents.

Background: Nowadays, the functional foods represent one the most promising, interesting and innovative areas in the food industry. Various components are being added to foods in order to render them functional. Methods: One example of these components are plant naturally occurring phenolic compounds, which are associated with a high antioxidant capacity and thus with benefits in relation to human health. Results: However, despite the huge number of scientific studies and patents on this topic and their natural presence in foods, namely in the ones from plant origin, there are still few marketable products enriched with these compounds. The commercialization of this type of functional products needs to go through various regulations, proving that they are safe and present the ascribed health benefits, conquering the target audience. In this review the growing interest of industry and consumers’ appetence for functional foods and nutraceuticals is highlighted, focusing especially on phenolic compounds. Conclusion: Although several published works show the multitude of bioactive properties of these compounds, ensuring their use as bioactive ingredients in food, they present inherent stability issues needing to be solved. However, considerable research is presently ongoing to overcome this problem, making viable the development of new products to be launched in the market.

Background: The mushroom Agaricus blazei has evoked considerable scientific and practical interest in several fields, especially those linked to its medicinal properties. This review aims to summarize and evaluate the past decade findings related to nutritional and therapeutic uses of A. blazei, with especial emphasis on the most recent discoveries regarding its chemical composition and clinical investigations. Methods: The specialized literature was searched for basic and clinical studies. The main isolated and identified compounds or fractions are described and confronted with their corresponding bioactivities. Results: Basic research of high quality using ex vivo and in vivo conditions are quite abundant in the specialized literature, but ony 17 clinical studies and two case reports were found. A great number of active molecules have been identified, and they can be divided into three categories, (1) hydrophilic small molecules (e.g., phenolics), (2) lipophilic or partially lipophilic small molecules (e.g., agarol) (3) and macromolecules (e.g., β-glucans). At least the following bioactivities can be considered as being supported by experimental evidence: antioxidant activity (in aging or disease), immunomodulation and cell signaling, anti-inflammatory activity, antiparasitic actions, antimicrobial activity, anticancer effects and tumor growth inhibiting effects, antimutagenic activity, hepatoprotection against chemical or viral infection and antidiabetic activity. Conclusion: The amount and quality of the evidence that has been accumulating during the last decade strongly speaks in favor of the health benefits of the ingestion of A.blazei or derived products. However, there are many uncertainties and limitations when attempts are made to extrapolate or to demonstrate their biological effects in the human organism in health or disease. Clearly, more clinical trials, using reliable statistical methods and standardized preparations are needed to establish the efficacy of A. blazei as a therapeutic agent.

Background: It is known that insufficient consumption of fiber in Western societies is directly linked to certain diseases. The required daily fiber intake can be obtained from foods such as fruits and vegetables, whole grains, legumes, nuts and others, or by eating foods enriched with fiber as a functional ingredient. Objective: This review studies certain fiber compounds such as oligosaccharides (namely α-galactosides and fructans), arabinoxylans and β-glucans. Results: The European regulatory body governing nutrition and health claims aims to protect consumers' right to receive truthful information about food by verifying statements on "nutrition", "content", "health claims" and "reducing the risk of disease". Some of these foods and functional ingredients can be considered as "novel foods". Conclusions: This paper describes the state of the art of certain fiber compounds and their effect on human health; the different requirements for fiber components used as functional or novel food ingredients; and the response of the European authorities to the use of this ingredient and its related health claims in terms of food labelling. After EFSA approval, these claims can be used in food labelling as an added value for consumer health, which may also improve their success in the market.

Background: Trends in modern pharmaceutical science show an increase in demand for new drugs and diet supplements derived from natural products, while during the last decades, great research is conducted regarding the natural compounds and their medicinal and bioactive properties. Organosulfur compounds are present in many plants and their bioactive properties have been used in folk and traditional medicine throughout the centuries. Not until recently, modern science confirmed and revealed the chemical compounds that are responsible for these properties, the chemistry involved in their biosynthesis and the main mechanisms of action. Objective: In the present review, the organosulfur compounds of vegetable origin and their health effects are presented, focusing on the chemical composition of their main compounds, their biosynthesis and the mechanisms involved in their health effects. Sulfur compound sources presented include mainly vegetable species belonging to Allium genus and Brassicaceae family. Conclusion: Organosulfur compounds of vegetable sources are very important in human diet, and their regular consumption has a beneficial contribution to health and well-being. Moreover, their medicinal properties and therapeutic effects have been described thousands of years ago, while they constitute an important ingredient in traditional medicines and preparations. However, not until recently, the mechanisms of action of organosulfur compounds have started to unravel, with promising results for further exploitation of these significant bioactive compounds in drug development and novel nutraceutical products. This review reveals the numerous biological activities of organosulfur compounds of vegetable origin, while it also presents the results of recent clinical studies and trials.

Background: Green tea is traditionally known to induce mental clarity, cognitive function, physical activation and relaxation. Recently, a special green tea, matcha tea, is rapidly gaining popularity throughout the world and is frequently referred to as a mood- and brain food. Matcha tea consumption leads to much higher intake of green tea phytochemicals compared to regular green tea. Previous research on tea constituents caffeine, L-theanine, and epigallocatechin gallate (EGCG) repeatedly demonstrated benefits on mood and cognitive performance. These effects were observed when these phytochemicals were consumed separately and in combination. Methods: A review was conducted on 49 human intervention studies to summarize the research on acute psychoactive effects of caffeine, L-theanine, and EGCG on different dimensions of mood and cognitive performance. Conclusion: Caffeine was found to mainly improve performance on demanding long-duration cognitive tasks and self-reported alertness, arousal, and vigor. Significant effects already occurred at low doses of 40 mg. L-theanine alone improved self-reported relaxation, tension, and calmness starting at 200 mg. L-theanine and caffeine combined were found to particularly improve performance in attention-switching tasks and alertness, but to a lesser extent than caffeine alone. No conclusive evidence relating to effects induced by EGCG could be given since the amount of intervention studies was limited. These studies provided reliable evidence showing that L-theanine and caffeine have clear beneficial effects on sustained attention, memory, and suppression of distraction. Moreover, L-theanine was found to lead to relaxation by reducing caffeine induced arousal.