Applications of Antioxidant Secondary Metabolites of Sargassum spp.

Sargassum is one of the largest and most diverse genus of brown seaweeds, comprising of around 400 taxonomically accepted species. Many species of this genus have long been a part of human culture with applications as food, feed, and remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of natural antioxidant compounds of great interest, including polyphenols, carotenoids, meroterpenoids, phytosterols, and several others. Such compounds provide a valuable contribution to innovation that can translate, for instance, into the development of new ingredients for preventing product deterioration, particularly in food products, cosmetics or biostimulants to boost crops production and tolerance to abiotic stress. This manuscript revises the chemical composition of Sargassum seaweeds, highlighting their antioxidant secondary metabolites, their mechanism of action, and multiple applications in fields, including agriculture, food, and health.

Overview of Phlorotannins' Constituents in Fucales.

Fucales are an order within the Phaeophyceae that include most of the common littoral seaweeds in temperate and subtropical coastal regions. Many species of this order have long been a part of human culture with applications as food, feedand remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of multiple bioactive compounds with great industrial interest. Among them, phlorotannins, a unique and diverse class of brown algae-exclusive phenolics, have gathered much attention during the last few years due to their numerous potential health benefits. However, due to their complex structural features, combined with the scarcity of standards, it poses a great challenge to the identification and characterization of these compounds, at least with the technology currently available. Nevertheless, much effort has been taken towards the elucidation of the structural features of phlorotannins, which have resulted in relevant insights into the chemistry of these compounds. In this context, this review addresses the major contributions and technological advances in the field of phlorotannins extraction and characterization, with a particular focus on Fucales.

Impact of Gastrointestinal Digestion on the Anti-Inflammatory Properties of Phlorotannins from Himanthalia elongata.

A phlorotannin extract was obtained from Himanthalia elongata, revealing a profile rich in fucophlorethol-type and carmalol-type compounds. When subjected to simulated gastrointestinal digestion, its levels of total phlorotannins and antioxidant activity, measured in vitro via NO● and O2●- scavenging assays, were reduced, thus suggesting that these compounds' integrity and bioactivity are negatively affected by the digestive process. Nevertheless, when undigested vs. digested extracts were used on lipopolysaccharide-stimulated Raw 264.7 macrophages, both showed a strong inhibitory effect on the cellular NO● production. In fact, although not statistically significant, the digested extract revealed a tendentially stronger effect compared to its undigested counterpart, suggesting that even though there is a decrease in the phlorotannins' concentration after digestion, with a consequent loss of their scavenging properties, the possible degradation products being formed may exert their effects through the modulation of the intracellular signaling mechanisms. Overall, this study not only contributes to a better understanding of the phlorotannins' composition of the species H. elongata, but also shows that, although the digestive process may affect the integrity and concentration of these compounds, this does not necessarily translate into loss of bioactivity, in particular the anti-inflammatory activity, probably owing to the bioactive effects that the degradation products of these phenolics may have at an intracellular level.

Impact of Circular Brewer's Spent Grain Flour after In Vitro Gastrointestinal Digestion on Human Gut Microbiota.

Brewer's spent grain (BSG) solid residues are constituted by dietary fibre, protein, sugars, and polyphenols, which can have potential effects on human health. In this study, for the first time, the flours obtained from solid residues of solid-liquid extraction (SLE) and ohmic heating extraction (OHE) were applied throughout the gastrointestinal digestion simulation (GID), in order to evaluate their prebiotic potential and in vitro human gut microbiota fermentation. The results showed that the digestion of BSG flours obtained by the different methods lead to an increase throughout the GID of total phenolic compounds (SLE: from 2.27 to 7.20 mg gallic acid/g BSG-60% ethanol:water (v/v); OHE: 2.23 to 8.36 mg gallic acid/g BSG-80% ethanol:water (v/v)) and consequently an increase in antioxidant activity (ABTS-SLE: from 6.26 to 13.07 mg ascorbic acid/g BSG-80% ethanol:water (v/v); OHE: 4.60 to 10.60 mg ascorbic acid/g BSG-80% ethanol:water (v/v)-ORAC-SLE: 3.31 to 14.94 mg Trolox/g BSG-80% ethanol:water (v/v); OHE: from 2.13 to 17.37 mg Trolox/g BSG-60% ethanol:water (v/v)). The main phenolic compounds identified included representative molecules such as vanillic and ferulic acids, vanillin and catechin, among others being identified and quantified in all GID phases. These samples also induced the growth of probiotic bacteria and promoted the positive modulation of beneficial strains (such as Bifidobacterium spp. and Lactobacillus spp.) present in human faeces. Moreover, the fermentation by human faeces microbiota also allowed the production of short chain fatty acids (acetic, propionic, and butyric). Furthermore, previous identified polyphenols were also identified during fecal fermentation. This study demonstrates that BSG flours obtained from the solid residues of SLE and OHE extractions promoted a positive modulation of gut microbiota and related metabolism and antioxidant environment associated to the released phenolic compounds.

Phlorotannins of the Brown Algae Sargassum vulgare from the Mediterranean Sea Coast.

Brown seaweeds are a good source of bioactive compounds, particularly of phlorotannins, which may exert a wide spectrum of pharmacological properties. In the present study, phlorotannins of S. vulgare were extracted using a 70% acetone solution and the crude extract was further purified through liquid-liquid partition, giving rise to n-hexane, ethyl acetate and aqueous residue fractions. The crude extract and the purified fractions were evaluated for potential antioxidant abilities as well as for inhibitory potential towards the digestive enzymes α-amylase and pancreatic lipase, and anti-inflammatory potential through the hindering of albumin denaturation. Overall, the ethyl acetate fraction was the richest in phlorotannins (9.4 ± 0.03 mg PGE/g) and was also the most promising regarding the tested bioactive properties. Of note, its inhibitory potential towards α-amylase was about nine times that of the commercial drug acarbose and its inhibitory activity against high temperature-induced protein denaturation was superior to that of the non-steroidal drug ketoprofen. According to UHPLC-DAD-ESI-MS/MS analysis, this fraction contained a range of phlorotannins with at least six units of phloroglucinol, including dibenzodioxine-1,3,6,8-tetraol, fuhalol, pentaphlorethol, fucopentaphlorethol and dihydroxypentafuhalol, in addition to several less common phlorotannin sulfate derivatives.

Pharmacological Properties of Bergapten: Mechanistic and Therapeutic Aspects.

Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and in vitro studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition, beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.

Impact of Phlorotannin Extracts from Fucus vesiculosus on Human Gut Microbiota.

Recent studies indicate that plant polyphenols could be pointed as potential prebiotic candidates since they may interact with the gut microbiota, stimulating its growth and the production of metabolites. However, little is known about the fate of brown seaweeds' phlorotannins during their passage throughout the gastrointestinal tract. This work aimed to evaluate the stability and bioaccessibility of Fucus vesiculosus phlorotannins after being submitted to a simulated digestive process, as well as their possible modulatory effects on gut microbiota and short-chain fatty acids production following a fermentation procedure using fecal inoculates to mimic the conditions of the large intestine. The stability of phlorotannins throughout the gastrointestinal tract was reduced, with a bioaccessibility index between 2 and 14%. Moreover, slight alterations in the growth of certain commensal bacteria were noticed, with Enterococcus spp. being the most enhanced group. Likewise, F. vesiculosus phlorotannins displayed striking capacity to enhance the levels of propionate and butyrate, which are two important short-chain fatty acids known for their role in intestinal homeostasis. In summary, this work provides valuable information regarding the behavior of F. vesiculosus phlorotannins along the gastrointestinal tract, presenting clear evidence that these compounds can positively contribute to the maintenance of a healthy gastrointestinal condition.

Antitumor Activity of Fucus vesiculosus-Derived Phlorotannins through Activation of Apoptotic Signals in Gastric and Colorectal Tumor Cell Lines.

Seaweeds are one of the largest producers of biomass in the marine environment and a source of multiple bioactive metabolites with valuable health benefits. Among these, phlorotannins have been widely recognized for their promising bioactive properties. The potential antitumor capacity of Fucus vesiculosus-derived phlorotannins remains, however, poorly explored, especially in gastrointestinal tract-related tumors. Therefore, this work aimed to evaluate the cytotoxic properties and possible mechanisms by which F. vesiculosus crude extract (CRD), phlorotannin-rich extract (EtOAc), and further phlorotannin-purified fractions (F1-F9) trigger cell death on different tumor cell lines of the gastrointestinal tract, using flow cytometry. The results indicate that F. vesiculosus samples exert specific cytotoxicity against tumor cell lines without affecting the viability of normal cells. Moreover, it was found that, among the nine different phlorotannin fractions tested, F5 was the most active against both Caco-2 colorectal and MKN-28 gastric cancer cells, inducing death via activation of both apoptosis and necrosis. The UHPLC-MS analysis of this fraction revealed, among others, the presence of a compound tentatively identified as eckstolonol and another as fucofurodiphlorethol, which could be mainly responsible for the promising cytotoxic effects observed in this sample. Overall, the results herein reported contribute to a better understanding of the mechanisms behind the antitumor properties of F. vesiculosus phlorotannin-rich extracts.

Brown Algae Phlorotannins: A Marine Alternative to Break the Oxidative Stress, Inflammation and Cancer Network.

According to the WHO, cancer was responsible for an estimated 9.6 million deaths in 2018, making it the second global leading cause of death. The main risk factors that lead to the development of this disease include poor behavioral and dietary habits, such as tobacco use, alcohol use and lack of fruit and vegetable intake, or physical inactivity. In turn, it is well known that polyphenols are deeply implicated with the lower rates of cancer in populations that consume high levels of plant derived foods. In this field, phlorotannins have been under the spotlight in recent years since they have shown exceptional bioactive properties, with great interest for application in food and pharmaceutical industries. Among their multiple bioactive properties, phlorotannins have revealed the capacity to interfere with several biochemical mechanisms that regulate oxidative stress, inflammation and tumorigenesis, which are central aspects in the pathogenesis of cancer. This versatility and ability to act either directly or indirectly at different stages and mechanisms of cancer growth make these compounds highly appealing for the development of new therapeutical strategies to address this world scourge. The present manuscript revises relevant studies focusing the effects of phlorotannins to counteract the oxidative stress-inflammation network, emphasizing their potential for application in cancer prevention and/or treatment.

Microwave-Assisted Extraction of Phlorotannins from Fucus vesiculosus.

Microwave-assisted extraction (MAE) was carried out to maximize the extraction of phlorotannins from Fucus vesiculosus using a hydroethanolic mixture as a solvent, as an alternative to the conventional method with a hydroacetonic mixture. Optimal MAE conditions were set as ethanol concentration of 57% (v/v), temperature of 75 °C, and time of 5 min, which allowed a similar recovery of phlorotannins from the macroalgae compared to the conventional extraction. While the phlorotannins richness of the conventional extract was slightly superior to that of MAE (11.1 ± 1.3 vs. 9.8 ± 1.8 mg PGE/g DWextract), both extracts presented identical phlorotannins constituents, which included, among others, tetrafucol, pentafucol, hexafucol, and heptafucol structures. In addition, MAE showed a moderate capacity to scavenge ABTS•+ (IC50 of 96.0 ± 3.4 µg/mL) and to inhibit the activity of xanthine oxidase (IC50 of 23.1 ± 3.4 µg/mL) and a superior ability to control the activity of the key metabolic enzyme α-glucosidase compared to the pharmaceutical drug acarbose.

Phlorotannins from Fucus vesiculosus: Modulation of Inflammatory Response by Blocking NF-κB Signaling Pathway.

Due to their large spectrum of bioactive properties, much attention has recently been drawn to phlorotannins-i.e., phenolic compounds characteristic from brown macroalgae. This study aimed to evaluate the antioxidant and anti-inflammatory properties of F. vesiculosus phlorotannin extracts and purified fractions. Overall, the crude extract and its ethyl acetate fraction (EtOAc) showed good radical scavenging activity, particularly towards nitric oxide (NO•). Subsequent subfractions of EtOAc (F1 to F9) with different molecular weights were then shown to inhibit lipopolysaccharide-induced NO• production in macrophages, with stronger effects being observed for fractions of lower MWs. Of the three intracellular markers analyzed, inducible NO• synthase showed the highest sensitivity to almost all the phlorotannin-rich samples, followed by interleukin 1ß and cyclooxygenase 2, which was only inhibited by F2. Furthermore, this subfraction inhibited the phosphorylation and degradation of inhibitory protein κBα, thus preventing the activation of NF-κB and blocking the inflammatory cascade at the transcriptional level. This sample was characterized by the presence of a major compound with a deprotonated molecular ion at m/z 507 with a fragmentation pattern coherent with that of a phlorotannin derivative. Overall, this work unveiled some of the mechanistic aspects behind the anti-inflammatory capacity of phlorotannins from F. vesiculosus, endorsing its use as a possible natural source of anti-inflammatory compounds.

Brown Macroalgae as Valuable Food Ingredients.

Due to the balanced nutritional value and abundance of bioactive compounds, seaweeds represent great candidates to be used as health-promoting ingredients by the food industry. In this field, Phaeophyta, i.e., brown macroalgae, have been receiving great attention particularly due to their abundance in complex polysaccharides, phlorotannins, fucoxanthin and iodine. In the past decade, brown algae and their extracts have been extensively studied, aiming at the development of well-accepted products with the simultaneous enhancement of nutritional value and/or shelf-life. However, the reports aiming at their bioactivity in in vivo models are still scarce and need additional exploration. Therefore, this manuscript revises the relevant literature data regarding the development of Phaeophyta-enriched food products, namely those focused on species considered as safe for human consumption in Europe. Hopefully, this will create awareness to the need of further studies in order to determine how those benefits can translate to human beings.

Optimization of Phlorotannins Extraction from Fucus vesiculosus and Evaluation of Their Potential to Prevent Metabolic Disorders.

Phlorotannins are phloroglucinol-based phenolic compounds, occurring particularly in brown macroalgae, that have been recognized for their promising bioactive properties. In this study, the extraction of phlorotannins from Fucus vesiculosus was evaluated with particular emphasis on the influential parameters, including the solvent concentration, solvent-solid ratio, extraction temperature and extraction time, using a single-factor design followed by a Box-Behnken design. The maximum total phlorotannin content, determined using the 2,4-dimethoxybenzaldehyde (DMBA) method, corresponded to 2.92 ± 0.05 mg of phloroglucinol equivalents/g dry seaweed (mg PGE/g DS), and was achieved for extracts carried out with acetone 67% (v/v), a solvent-solid ratio of 70 mL/g and temperature at 25 °C. This crude extract, together with a semi-purified phlorotannin fraction, were further evaluated for their anti-enzymatic capacity against α-glucosidase, α-amylase and pancreatic lipase, both showing promising inhibitory effects, particularly against α-glucosidase for which a greater inhibitory effect was observed compared to the pharmaceutical drug acarbose (IC50 = 4.5 ± 0.8 and 0.82 ± 0.3 µg/mL, respectively, against 206.6 ± 25.1 µg/mL). Additionally, the ultra-high-pressure liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis carried out on the ethyl acetate fraction revealed the presence of fucols, fucophlorethols, fuhalols and several other phlorotannin derivatives. Moreover, possible new phlorotannin compounds, including fucofurodiphlorethol, fucofurotriphlorethol and fucofuropentaphlorethol, have been tentatively identified in this extract. Overall, this study provides evidence that F. vesiculosus phlorotannin-rich extracts hold potential for the management of the activity of α-glucosidase, α-amylase and pancreatic lipase, which are well known to be linked to metabolic disorders such as diabetes and obesity.

Salvia elegans, Salvia greggii and Salvia officinalis Decoctions: Antioxidant Activities and Inhibition of Carbohydrate and Lipid Metabolic Enzymes.

Salvia elegans Vahl., Salvia greggii A. Gray, and Salvia officinalis L. decoctions were investigated for their health-benefit properties, in particular with respect to antioxidant activity and inhibitory ability towards key enzymes with impact in diabetes and obesity (α-glucosidase, α-amylase and pancreatic lipase). Additionally, the phenolic profiles of the three decoctions were determined and correlated with the beneficial properties. The S. elegans decoction was the most promising in regard to the antioxidant effects, namely in the scavenging capacity of the free radicals DPPH•, NO• and O2•⁻, and the ability to reduce Fe3+, as well as the most effective inhibitor of α-glucosidase (EC50 = 36.0 ± 2.7 µg/mL vs. EC50 = 345.3 ± 6.4 µg/mL and 71.2 ± 5.0 µg/mL for S. greggii and S. officinalis, respectively). This superior activity of the S. elegans decoction over those of S. greggii and S. officinalis was, overall, highly correlated with its richness in caffeic acid and derivatives. In turn, the S. officinalis decoction exhibited good inhibitory capacity against xanthine oxidase activity, a fact that could be associated with its high content of flavones, in particular the glycosidic forms of apigenin, scutellarein and luteolin.

Minerals from Macroalgae Origin: Health Benefits and Risks for Consumers.

Seaweeds are well-known for their exceptional capacity to accumulate essential minerals and trace elements needed for human nutrition, although their levels are commonly very variable depending on their morphological features, environmental conditions, and geographic location. Despite this variability, accumulation of Mg, and especially Fe, seems to be prevalent in Chlorophyta, while Rhodophyta and Phaeophyta accumulate higher concentrations of Mn and I, respectively. Both red and brown seaweeds also tend to accumulate higher concentrations of Na, K, and Zn than green seaweeds. Their valuable mineral content grants them great potential for application in the food industry as new ingredients for the development of numerous functional food products. Indeed, many studies have already shown that seaweeds can be used as NaCl replacers in common foods while increasing their content in elements that are oftentimes deficient in European population. In turn, high concentrations of some elements, such as I, need to be carefully addressed when evaluating seaweed consumption, since excessive intake of this element was proven to have negative impacts on health. In this regard, studies point out that although very bioaccessible, I bioavailability seems to be low, contrarily to other elements, such as Na, K, and Fe. Another weakness of seaweed consumption is their capacity to accumulate several toxic metals, which can pose some health risks. Therefore, considering the current great expansion of seaweed consumption by the Western population, specific regulations on this subject should be laid down. This review presents an overview of the mineral content of prevalent edible European macroalgae, highlighting the main factors interfering in their accumulation. Furthermore, the impact of using these marine vegetables as functional ingredients or NaCl replacers in foods will be discussed. Finally, the relationship between macroalgae's toxic metals content and the lack of European legislation to regulate them will be addressed.

Phycochemical Constituents and Biological Activities of Fucus spp.

Seaweeds are known to be a good supply of key nutrients including carbohydrates, protein, minerals, polyunsaturated lipids, as well as several other health-promoting compounds capable of acting on a wide spectrum of disorders and/or diseases. While these marine macroalgae are deeply rooted in the East Asian culture and dietary habits, their major application in Western countries has been in the phycocolloid industry. This scenario has however been gradually changing, since seaweed consumption is becoming more common worldwide. Among the numerous edible seaweeds, members of the genus Fucus have a high nutritional value and are considered good sources of dietary fibers and minerals, especially iodine. Additionally, their wealth of bioactive compounds such as fucoidan, phlorotannins, fucoxanthin and others make them strong candidates for multiple therapeutic applications (e.g., antioxidant, anti-inflammatory, anti-tumor, anti-obesity, anti-coagulant, anti-diabetes and others). This review presents an overview of the nutritional and phytochemical composition of Fucus spp., and their claimed biological activities, as well as the beneficial effects associated to their consumption. Furthermore, the use of Fucus seaweeds and/or their components as functional ingredients for formulation of novel and enhanced foods is also discussed.

Plant Growth Modulates Metabolites and Biological Activities in Retama raetam (Forssk.) Webb.

This work focuses on the variability of Retama raetam (Forssk.) Webb bioactive compounds as a function of the plant cycle. The main results showed that it exhibited the highest percentage of polyunsaturated fatty acids, along with superior levels of vitamin C and total phenolic compounds (66.49%, 645.6 mg·100 g-¹ FW and 23.9 mg GAE·g-¹, respectively) at the vegetative stage. Instead, at the flowering and mature fruiting stages, R. raetam (Forssk.) Webb exhibited notable contents of proline (25.4 µmol·g-¹ DW) and carotenoids (27.2 µg·g-¹ FW), respectively. The gathered data concerning the antioxidant activity highlighted the effectiveness of the vegetative stage in comparison to the other periods. Actually, IC50 and EC50 values of the hydromethanolic extract obtained from the plant shoots at the vegetative stage were of 23, 380, 410, 1160 and 960 µg·mL-1 (DPPH• and ABTS•+ radicals scavenging activity, reducing power, chelating power and ß-carotene bleaching activity, respectively). Furthermore, the four studied stages showed appreciable antibacterial capacities against human pathogens with a higher efficiency of the vegetative stage extract. Finally, the LC-DAD-ESI/MSn analysis revealed the predominance of isoflavonoids as main class of phenolic compounds and demonstrates that individual phenolic biosynthesis was clearly different as a function of plant growth. These findings highlight that reaching the optimum efficiency of R. raetam (Forssk.) Webb is closely linked to the physiological stage.

Antioxidant and anti-inflammatory activities of Geranium robertianum L. decoctions.

Geranium robertianum L., commonly known as Herb Robert, is an herbaceous plant popularly known for its functional properties including antioxidant and anti-inflammatory activities. In this study, the phenolic profile of leaf and stem decoctions of Geranium robertianum L. was elucidated by UHPLC-DAD-ESI-MSn analysis, and their antioxidant and anti-inflammatory potentials were assessed in vitro. Importantly, and envisaging the use of these extracts in human diets, the potential toxicity of bioactive concentrations was also addressed in macrophages and hepatocytes. Both extracts revealed high amounts of ellagitannins, although a slight prevalence of these compounds was observed in that originating from leaves. High radical scavenging activities against DPPH˙, ABTS˙+ and OH˙ were observed either for the leaf or the stem extract, as well as good activities towards ferric reducing antioxidant power, lipid peroxidation and oxygen radical absorbance capacity. In addition, both extracts were very effective at scavenging NO˙, as measured in a chemical model, while only the stem extract was able to decrease the production of this radical by stimulated macrophages. On the other hand, none of the extracts was able to modulate the activity of lipoxygenase or the expression of the inducible nitric oxide synthase. Overall, these data allowed us to conclude that G. robertianum L. stem and leaf decoctions are particularly rich in tannins. The strong scavenging effects displayed by the stem extract suggest that its anti-inflammatory activity may partially result from its anti-radical capacities towards NO˙.

Fucaceae: A Source of Bioactive Phlorotannins.

Fucaceae is the most dominant algae family along the intertidal areas of the Northern Hemisphere shorelines, being part of human customs for centuries with applications as a food source either for humans or animals, in agriculture and as remedies in folk medicine. These macroalgae are endowed with several phytochemicals of great industrial interest from which phlorotannins, a class of marine-exclusive polyphenols, have gathered much attention during the last few years due to their numerous possible therapeutic properties. These compounds are very abundant in brown seaweeds such as Fucaceae and have been demonstrated to possess numerous health-promoting properties, including antioxidant effects through scavenging of reactive oxygen species (ROS) or enhancement of intracellular antioxidant defenses, antidiabetic properties through their acarbose-like activity, stimulation of adipocytes glucose uptake and protection of ß-pancreatic cells against high-glucose oxidative stress; anti-inflammatory effects through inhibition of several pro-inflammatory mediators; antitumor properties by activation of apoptosis on cancerous cells and metastasis inhibition, among others. These multiple health properties render phlorotannins great potential for application in numerous therapeutical approaches. This review addresses the major contribution of phlototannins for the biological effects that have been described for seaweeds from Fucaceae. In addition, the bioavailability of this group of phenolic compounds is discussed.

Antioxidant capacities of flavones and benefits in oxidative-stress related diseases.

Flavonoids, a group of secondary metabolites widely distributed in the plant kingdom, have been acknowledged for their interesting medicinal properties. Among them, natural flavones, as well as some of their synthetic derivatives, have been shown to exhibit several biological activities, including antioxidant, anti-inflammatory, antitumor, anti-allergic, neuroprotective, cardioprotective and antimicrobial. The antioxidant properties of flavones allow them to demonstrate potential application as preventive and attenuating agents in oxidative stress, i.e., a biological condition that is closely associated to aging process and several diseases. Some flavones interfere in distinct oxidative-stress related events by directly reducing the levels of intracellular free radicals (hydroxyl, superoxide and nitric oxide) and/or of reactive species (e.g. hydrogen peroxide, peroxynitrite and hypochlorous acid) thus preventing their amplification and the consequent damage of other biomolecules such as lipids, proteins and DNA. Flavones can also hinder the activity of central free radical-producing enzymes, such as xanthine oxidase and nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) or inducible nitric oxide synthase (iNOS) and can even modulate the intracellular levels of pro-oxidant and/or antioxidant enzymes. The evaluation of flavones antioxidant ability has been extensively determined in chemical or biological in vitro models, but in vivo therapy with individual flavones or with flavones-enriched extracts has also been reported. The present manuscript revises relevant studies focusing the preventive effects of flavones on stress-related diseases, namely the neurological and cardiovascular diseases, and diabetes and its associated complications.