A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives

Many studies have been conducted with regard to free radicals, oxidative stress and antioxidant activity of food, giving antioxidants a prominent beneficial role, but, recently many authors have questioned their importance, whilst trying to understand the mechanisms behind oxidative stress. Many scientists defend that regardless of the quantity of ingested antioxidants, the absorption is very limited, and that in some cases prooxidants are beneficial to human health. The detection of antioxidant activity as well as specific antioxidant compounds can be carried out with a large number of different assays, all of them with advantages and disadvantages. The controversy around antioxidant in vivo benefits has become intense in the past few decades and the present review tries to shed some light on research on antioxidants (natural and synthetic) and prooxidants, showing the potential benefits and adverse effects of these opposing events, as well as their mechanisms of action and detection methodologies. It also identifies the limitations of antioxidants and provides a perspective on the likely future trends in this field.Fundação para a Ciência e a Tecnologia (FCT, Portugal) and COMPETE/QREN/EU for financial support to CIMO (strategic project PEst-OE/AGR/UI0690/2011)

Neurocognitive improvement through plant food bioactives: A particular approach to Alzheimer's disease

Alzheimer’s disease (AD) is currently one of the most prevalent neurodegenerative disorders, directly related to increasing rates of morbidity and autonomy impairment between worldwide citizens. Social and demographical changes are direct contributors; notwithstanding, modern lifestyle, oxidative stress and its related diseases, and, consequently, premature aging are also important triggering factors (Sun et al. 2008; Ngo and Li 2013). Numerous drugs have been developed mainly to act as symptomatic agents, despite the serious side effects and increasing evidences of lack of effectiveness. Most of them were derived from plant-mimetic synthesis, but tenuous differences on their chemical structure and also the occurrence of synergisms in the pool of the whole plant phytochemicals are sufficient to provide considerable influences on the final biological potential (Ngo and Li 2013; Katalini et al. 2014; Ahmed et al. 2015). The use of medicinal plants, mainly through botanical preparations, is a millenary practice, which has been effectively used for a multitude of health conditions (Vanaclocha and Cañigueral 2003; Murray 2004; Murray and Pizzorno 2012). The interest for natural matrices is still increasing, not only to confirm its bioactive potential, but also to deepen knowledge on the modes of action, metabolism, bioavailability, bioefficacy, and active concentrations, aiming to develop upcoming and safer alternatives to the current ones. Among them, plant phytochemicals have shown to have promissory neurocognitive properties. In this sense, the present chapter aims to provide systematic information about the use of plant-food-derived bioactive molecules with evident in vitro and in vivo neuroprotective and neuroregenerative effects.info:eu-repo/semantics/publishedVersio

Phytochemicals and their effects on human health

The knowledge about the medicinal properties of natural products, including their action as healthy diet promotors, is widely recognized. Currently, the evidences that natural matrices possess specific bioactive properties, afforded by their chemical constituents, have become increasingly clear for the scientific community. Nevertheless, evidences from clinical trials and epidemiologic observations are still demanded namely regarding the ideal time of the treatment and doses of the selected species. Regardless of the increasing recognition of natural matrices health evidences, a higher prevalence of chronic and degenerative diseases have been observed as a direct consequence of the undergoing socioeconomic improvement. The fact that natural matrices are a source of bioactive compounds, such as polyphenols, vitamins, carotenoids and unsaturated fatty acids, stimulates its usage in several areas. In addition to the benefits associated with its direct use in the food industry, they may be used as ingredients in the formulation of functional foods, nutraceuticals and in the pharmaceutical industry, for the production of natural drugs (representing a significant portion of the global pharmaceutical market production). Due to the chemical, nutritional and medicinal properties of these matrices, in recent years there has been an increasing interest in exploiting their applications in health disorders conventionally treated with chemically synthesized products. These therapeutic properties associated to the fact that natural products have fewer adverse or side effects have triggered various scientific studies aiming to validate the use of biologically active substances that can be extracted from these valuable natural sources and justify the worthiness of the ongoing and future research in this field.info:eu-repo/semantics/publishedVersio

The role of phenolic compounds in the fight against cancer – a review

Cancer is a worldwide scourge; it’s the leading cause of death in developed countries and is increasing in developing countries. Mankind has been trying with effort to find better and cheaper treatments with fewer side effects, to reduce the incidence of the disease and its consequent mortality. For many years, phenolic compounds have been intensely studied for their antitumor, proapoptotic and antiangiogenic effects. In recent years, the usage of these compounds has increased considerably. This manuscript intends to structurally characterize the different phenolic compounds (flavonoids, hydroxycinnamates, hydroxybenzoates, coumarins, xanthones, chalcones, stilbenes, lignins and lignans) and their metabolic pathways as well as review the most important results regarding these compounds and their derivatives in cancer treatment and prevention both in tumor cell lines in vitro, in murine models in vivo and finally some results regarding human trials.Fundação para a Ciência e a Tecnologia (FCT, Portugal) and COMPETE/QREN/EU for research project PTDC/AGR-ALI/110062/2009 and to CIMO (strategic project PEst-OE/AGR/UI0690/2011)

Stress oxidativo, antioxidantes e fitoquímicos

A manutenção do equilíbrio entre a produção de radicais livres e as defesas antioxidantes (enzimas e moléculas não enzimáticas) é uma condição essencial para o funcionamento normal do organismo. Quando este equilíbrio tende para a produção de radicais livres dizemos que o organismo está em stress oxidativo, e nestas situações os radicais livres em excesso podem oxidar e danificar lípidos celulares, proteínas e DNA, inibindo a sua função normal e conduzindo a várias doenças. Em organismos aeróbios, os radicais livres são constantemente produzidos durante o funcionamento normal da célula, na maior parte sob a forma de espécies reactivas de oxigénio (ROS) e de nitrogénio (RNS). A exposição dos organismos a radicais livres, conduziu ao desenvolvimento de mecanismos de defesa endógenos para os eliminar. Estas defesas são a resposta da evolução à inevitabilidade da existência de ROS em condições aeróbias. Alguns produtos naturais com actividade antioxidante, podem auxiliar o sistema protector endógeno. Nesta perspectiva, os antioxidantes presentes na dieta assumem grande importância como possíveis agentes protectores, reduzindo os danos oxidativos. São aqui descritos alguns desses agentes antioxidantes, os fitoquímicos, compostos bioactivos provenientes de diferentes partes de plantas (sementes, cereais, vegetais, frutos, folhas, raízes, especiarias, ervas) envolvidos na redução do risco de doença, como o cancro. Foram já identificados mais de 5000 fitoquímicos, no entanto, grande parte destes compostos é ainda desconhecida, sendo a sua identificação essencial para a compreensão da sua contribuição na saúde, ao serem incluídos na dieta. Maintenance of equilibrium between free radical production and antioxidant defences (enzymatic and non enzymatic) is an essential condition for normal organism functioning. When this equilibrium has a tendency to the production of free radical we say that the organism is in oxidative stress. In this situation, excess free radicals may damage cellular lipids, proteins and DNA, inhibiting his normal function and leading to various diseases. In aerobic organisms, the free radicals are constantly being produced during the normal cellular functioning, mainly in the form of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). Exposition of the organism to free radicals has led to the development of endogenous defence mechanisms to eliminate them. These defences were the response of evolution to the inevitability of ROS production in aerobic conditions. Natural products with antioxidant activity may help the endogenous defence system. In this perspective the antioxidant present on the diet assume a major importance as possible protector agents reducing oxidative damage. Phytochemicals with antioxidant activity, obtained from different plant parts (seeds, cereals, vegetables, fruits, leaves, roots, spices, herbs), and involved in disease risk reduction are review. More than 5000 phytochemicals were already discovered, but most of these compounds remain yet to be discovered. Their identification and the study of their contribution to health is essential

Farnesoid X Receptor as a potential protein target for mushroom LMW compounds: virtual screening using molecular docking

Farnesoid X receptor (FXR) is a nuclear receptor protein involved in controlling several metabolic pathways, with bile acids as his natural ligands. FXR functions as a sensor for bile acids, thus promoting their clearance by controlling expression of genes involved in bile acids transport and metabolism. FXR has been recently regarded as an important target for drug discovery and the research for small molecules, that modulates his interaction with binding co-regulator proteins, is ongoing. Very recently, several reports have shown natural compounds and extracts with activity as, either agonists or antagonists of FXR, notably steroids (1) and polyphenols (2). Mushrooms have been widely recognised as presenting in their chemical constitution polyphenols and steroids in significant amounts, either in quantity and diversity. For this reason we set out to investigate FXR as a potential target for LMW compounds present in mushrooms. To meet this goal we virtually screened a database of 40 compounds, present in mushrooms, against a carefully prepared 3D crystal structure of FXR (PDB code: 1OIV). The molecular docking software used for this virtual screening project was AutoDock Vina (VINA) and the database of LMW compounds were revised and prepared by us. VINA presents the results as predΔG (predicted binding energy), with compounds with the lowest predΔG expected to be the ones with more potent FXR modulating activity. Among the tested compounds, steroids presented the lowest predΔG, with several displaying values below -10 kcal/mol including: Ergosta-4,6,8(14),22-tetraen-3-one (-10,5 kcal/mol), Ganoderic acid A (-10,4 kcal/mol), Ganoderic acid A (-10,3 kcal/mol) and Ergosterol (-10,2 kcal/mol). These results are not unexpected, as FXR natural ligands are in fact bile acids, that belong to the steroid class of compounds. Also, the predΔG values of the top ranked steroids compared well with the predΔG value of a benzamide derivative compound (10,6 kcal/mol), a known inhibitor of FXR that is co-crystallized in the 1OIV crystal structure. In conclusion, this initial study points to FXR as a potential target for mushroom compounds and extracts, especially steroid derivatives or extracts. Although further studies are needed to confirm this hypothesis, this work demonstrates the usefulness of using an in silico approach as a complement for experimental work.info:eu-repo/semantics/publishedVersio

Aditivos antioxidantes

La química entre los radicales libres y antioxidantes se fundamenta en un equilibrio entre ambos. Los radicales libres son compuestos muy reactivos que tienden a captar un electrón de moléculas biológicas estables con el fin de alcanzar su estabilidad electroquímica. Una vez que el radical libre ha conseguido sustraer el electrón que necesita, la molécula estable que se lo cede se convierte, a su vez, en un radical libre al quedarse con un electrón desapareado, iniciándose así una verdadera reacción en cadena. La vida media biológica dei radical libre es de microsegundos, pêro tiene la capacidad de reaccionar con todo lo que este a su alrededor provocando dano molecular en membranas celulares y tejidos. Los radicales libres se pueden definir como "cualquier espécie química con un número impar de electrones, con uno o más electrones desapareados, que se encuentra de forma libre en el médio".info:eu-repo/semantics/publishedVersio

Extraction and detection of mycotoxins in medicinal and aromatic plants: a case studywith Melissa officinalis L.

Plants frequently suffer contaminations by toxigenic fungi, and their mycotoxins can be produced throughout growth, harvest, drying and storage periods. The objective of this work was to validate a method for detection of toxins in medicinal and aromatic plants, through a fast and highly sensitive method, optimizing the joint eo-extraction of aflatoxins (AF: AFB1, AFB2, AFG1 and AFG2) and ochratoxin A (OTA) by using Aloysia citrodora P. (lemon verbena) as a case study. For optimization purposes, samples were spiked (n=3) with standard solutions of a mix of the four AFs and OTA at 10 ng/g for AFB1, AFG1 and OTA, and at 6 ng/g of AFB2 and AFG2. Several extraction procedures were tested: i) ultrasound-assisted extraction in sodium chloride and methanol/water (80:20, v/v) [(OTA+AFs)1]; ii) maceration in methanol/1% NaHC03 (70:30, v/v) [(OTA+AFs)2]; iii) maceration in methanol/1% NaHC03 (70:30, v/v) (OTA1); and iv) maceration in sodium chloride and methanol/water {80:20, v/v) (AF1). AF and OTA were purified using the mycotoxin-specific immunoaffinity columns AflaTest WB and OchraTest WB (VICAM), respectively. Separation was performed with a Merck Chromolith Performance C18 column (100 x 4.6 mm) by reverse-phase HPLC coupled to a fluorescence detector (FLD) and a photochemical derivatization system (for AF). The recoveries obtained from the spiked samples showed that the single-extraction methods (OTA1 and AF1) performed better than eoextraction methods. For in-house validation of the selected methods OTA1 and AF1, recovery and precision were determined (n=6). The recovery of OTA for metl:lod OTA1 was 81%, and intermediate precision (RSDint) was 1.1%. The recoveries of AFB1, AFB2, AFG1 and AFG2 ranged from 64% to 110% for method AF1, with RSDint lower than 5%. Methods OTA1 and AF1 showed precision and recoveries within the legislated values and were found to be suitable for the extraction of OTA and AF for the matrix under study

Medicinal chemistry from fungi and back: discovery of novel anti-fungal drugs and mycotherapy of cancer and other diseases with fungal metabolites

Fungi are important organisms for human population and could find important applications namely, in many pharmaceutical and food industries. A variety of compounds has been isolated from medicinal and edible mushrooms, and their healthbeneficial effects have been reported. On the other hand, it is important to control microfungi as parasites and contaminants since they can provoke, in some cases, serious issues to human health. The following issue is devoted to recent findings in the fields of novel antifungal drugs, mycotherapy of cancer and other diseases with compounds recently isolated from fungi. It is covered by eight hot topic manuscripts from the mentioned relevant fields. A review on antifungal activity of mushrooms (Basidiomycetes) and their isolated compounds including high (e.g. peptides and proteins) and low (e.g. sesquiterpenes and other terpenes, steroids, organic acids, acylcyclopentenediones and quinolines) molecular weight compounds is presented. Furthermore, antioxidant protective effects of mushroom metabolites is presented covering antioxidant features of numerous compounds isolated from mushrooms, such as phenolic compounds, vitamins, polysaccharides, peptides, proteins, organic acids, carotenoids, alkaloids, and nucleotides. Cyclodextrins are usually used in antifungal formulations as auxiliary substances to improve solubility, stability, or other physicochemical properties of the active compound. Nevertheless, recent research and practical use results indicate that cyclodextrins might also act as active compounds in pharmaceutical formulations. Furthermore, Recent advances in synthesis of compounds and their biological evaluation considering antifungal activity is also presented, covering the broad spectrum of compounds from different chemical classes. Therapeutic properties of mushrooms in managing adverse effects in the metabolic syndrome deeply discusses the use of edible mushrooms, their extracts, polysaccharide fractions and isolated compounds as hypoglycaemic agents, as holders of cholesterol and triglyceride lowering ability, hypotensive agents, as well as weight managing holders. New and highly potent antitumor natural products from marine-derived fungi presents recent finding on cytotoxic activities of fungal compounds. Essential oils for the control of fungi and the production of aflatoxins, especially the most toxic aflatoxins B1 and G1, is essential and decisive, therefore highlighting the possibilities of utilizing essential oils in biological control of aflatoxin contamination. The last paper focuses on recent update of cytotoxic and antitumor activity of mushroom extracts and compounds belonging to the heteropolysaccharides, β-glucans, α-glucans, proteins, complexes of polysaccharides with proteins, fatty acids, nucleoside antagonists, terpenoids, sesquiterpenes, lanostanoids, sterols and phenolic compounds. Molecular mechanisms of cytotoxic and antitumor activities are briefly discussed

Chemical composition of Lactarius sp. mushrooms in different maturity stages.

Wild mushrooms are becoming more and more important in our diet for fheir nutritional value, inciuding high pratein and low fat/energy contenfs [1], Dikeman et 01, [2] reported lhe effects of stage o f maturity and cooking on the chemical composition of mushroom species commonly cultivated and consumed in the United Sfates, Nevertheless, there are no detailed studies on the influence in fatty acid and sugars pro flles, partic ularly on mushrooms from Northeast Portugal