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.

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.

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.

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.