Marine Polyphenols Research Articles

Marine Polyphenols in Cardiovascular Health: Unraveling Structure-Activity Relationships, Mechanisms, and Therapeutic Implications.

Cardiovascular diseases (CVDs) are responsible for significant mortality rates globally that have been raised due to the limitation of the available treatments and prevalence of CVDs. The innovative research and identification of potential preventives for CVDs are essential to alleviate global deaths and complications. The marine environment is a rich source of bioactive substances and provides a unique chemical arsenal against numerous ailments due to its unrivaled biodiversity. Marine polyphenolic compounds (MPCs) are unique because of their structural variety and biologically significant activity. Further, MPCs are well-reported for their valuable biological activities, such as anti-inflammatory, cardioprotective, and antioxidant, demonstrating encouraging results in preventing and treating CVDs. Therefore, investigation of the structure-activity relationship (SAR) between MPCs and CVDs provides insights that reveal how the structural components of these compounds affect their effectiveness. Further, comprehending this correlation is essential for advancing medications and nutraceuticals sourced from marine sources, which could transform the strategy for treating and preventing cardiovascular diseases. Therefore, this study provides a comprehensive analysis of existing research by emphasizing the role of MPCs in CVD treatments and evaluating the SAR between MPCs and CVDs with challenges and future directions.

Investigating the Potential Anti-Alzheimer's Disease Mechanism of Marine Polyphenols: Insights from Network Pharmacology and Molecular Docking.

Marine polyphenols, including eckol(EK), dieckol(DK), and 8,8'-bieckol(BK), have attracted attention as bioactive ingredients for preventing Alzheimer's disease (AD). Since AD is a multifactorial disorder, the present study aims to provide an unbiased elucidation of unexplored targets of AD mechanisms and a systematic prediction of effective preventive combinations of marine polyphenols. Based on the omics data between each compound and AD, a protein-protein interaction (PPI) network was constructed to predict potential hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to provide further biological insights. In the PPI network of the top 10 hub genes, AKT1, SRC, EGFR, and ESR1 were common targets of EK and BK, whereas PTGS2 was a common target of DK and BK. GO and KEGG pathway analysis revealed that the overlapped genes between each compound and AD were mainly enriched in EGFR tyrosine kinase inhibitor resistance, the MAPK pathway, and the Rap1 and Ras pathways. Finally, docking validation showed stable binding between marine polyphenols and their top hub gene via the lowest binding energy and multiple interactions. The results expanded potential mechanisms and novel targets for AD, and also provided a system-level insight into the molecular targets of marine polyphenols against AD.

Therapeutic Potential of Polyphenols and Other Micronutrients of Marine Origin.

Polyphenols are compounds found in various plants and foods, known for their antioxidant and anti-inflammatory properties. Recently, researchers have been exploring the therapeutic potential of marine polyphenols and other minor nutrients that are found in algae, fish and crustaceans. These compounds have unique chemical structures and exhibit diverse biological properties, including anti-inflammatory, antioxidant, antimicrobial and antitumor action. Due to these properties, marine polyphenols are being investigated as possible therapeutic agents for the treatment of a wide variety of conditions, such as cardiovascular disease, diabetes, neurodegenerative diseases and cancer. This review focuses on the therapeutic potential of marine polyphenols and their applications in human health, and also, in marine phenolic classes, the extraction methods, purification techniques and future applications of marine phenolic compounds.

Marine Macroalgae Polyphenols as Potential Neuroprotective Antioxidants in Neurodegenerative Diseases

Polyphenols are beneficial natural compounds with antioxidant properties that have recently gain a lot of interest for their potential therapeutic applications. Marine polyphenols derived from marine macroalgae have been discovered to possess interesting antioxidant properties; therefore, these compounds can be included in several areas of drug development. Authors have considered the use of polyphenol extracts from seaweeds as neuroprotective antioxidants in neurodegenerative diseases. Marine polyphenols may slow the progression and limit neuronal cell loss due to their antioxidant activity; therefore, the use of these natural compounds would improve the quality of life for patients affected with neurodegenerative diseases. Marine polyphenols have distinct characteristics and potential. Among seaweeds, brown algae are the main sources of polyphenols, and present the highest antioxidant activity in comparison to red algae and green algae. The present paper collects the most recent in vitro and in vivo evidence from investigations regarding polyphenols extracted from seaweeds that exhibit neuroprotective antioxidant activity. Throughout the review, oxidative stress in neurodegeneration and the mechanism of action of marine polyphenol antioxidant activity are discussed to evidence the potential of algal polyphenols for future use in drug development to delay cell loss in patients with neurodegenerative disorders.

Acute and Repeated Dose 28-Day Oral Toxicity Studies of Phlorotannin Rich Fraction of <i>Sargassum tenerrimum</i>, A Marine Brown Algae

Sargassum tenerrimum is a marine brown algae rich in phlorotannins, a class of marine polyphenols with significant biological activities. The present study aimed to prepare a phlorotannin-rich fraction from S. tenerrimum (PST) and evaluate its acute and subacute oral toxicity in Wistar albino rats according to the procedures and methods of the OECD test guidelines for acute and repeated dose 28-day oral toxicity studies. S. tenerrimum powder was extracted with ethanol and further fractionated with ethylacetate, 1-butanol, and water. The ethyl acetate fraction was found to have the highest total phlorotannin concentration and was evaluated for its safety. In the acute oral toxicity study, a single dose of PST at 2000 mg/kg body weight did not result in any treatment-related clinical symptoms of toxicity or mortality. Therefore, the median lethal dose (LD50) of PST was identified as greater than 2000 mg/kg. The subacute oral toxicity investigation at 200, 400, and 800 mg/kg doses administered for 28 days with a 14-day recovery period revealed no treatment-related adverse clinical symptoms or mortality/morbidity. The treated animals exhibited normal weight gain, feed intake and did not result in clinically significant toxicity as measured by clinical blood chemistry and hematological markers. Gross and histological examinations of selected tissues did not reveal any notable adverse alterations associated with the intervention. Under the study's findings, the LD50 for PST was determined to be >2000 mg/kg b.wt. and No Observed Adverse Effect Level (NOAEL) to be 800 mg/kg rat b.wt.

Marine Polyphenol Phlorotannins as a Natural Sleep Aid for Treatment of Insomnia: A Review of Sedative-Hypnotic Effects and Mechanism of Action.

Insomnia is a common sleep disorder. Natural sleep aids are gaining worldwide popularity as alternatives to prescription drugs for improving sleep. Recently, numerous studies have investigated the sedative-hypnotic effects of the polyphenols of terrestrial plants. The hypnotic effects of marine polyphenols have also been studied in recent years. Phlorotannins are marine polyphenols that are found only in brown algae. Phlorotannins exert sedative-hypnotic effects via the gamma-aminobutyric acid type A-benzodiazepine receptor. In addition, the brown seaweed Ecklonia cava supplement containing phlorotannins has been approved by the Ministry of Food and Drug Safety as a health-functional ingredient that helps improve sleep quality. Currently, it is meaningful to deal with the sedative-hypnotic effects of phlorotannins as natural sleep aids. The current review comprehensively presents the sedative-hypnotic effects in animal models and human clinical trials as well as their mechanism of action, extraction, purification, and safety.

Facile synthesis of fluorescent mesoporous nanocarriers with pH-sensitive controlled release of naturally derived dieckol

Dieckol is a marine polyphenol found in the brown algae Ecklonia cava and has been actively studied because it has various biological activities such as antioxidant, anti-inflammatory, and antibacterial. Herein, fluorescent mesoporous silica nanoparticles (FMSNs) were synthesized for the efficient delivery of naturally derived Die molecules. The Die-loaded FMSNs (FMSNs-Die) were further coated with polyethylene glycol (PEG) and graphene oxide (GO) nanosheets, termed as FMSNs-Die@PEG and FMSNs-Die@PEG@GO, respectively. The release kinetics was investigated using Fickian-type exponential and Kosmeyer-Peppas relaxation models. Overall, the FMSN-based nanocarriers exhibited a faster release at pH 4.5 than at pH 7.4. The release rate at pH 7.4 decreased in the following order: FMSNs-Die > FMSNs-Die@PEG > FMSNs-Die@PEG@GO. In contrast, the release rate at pH 4.5 exhibited a somewhat different order of FMSNs-Die@PEG ≥ FMSNs-Die > FMSNs-Die@PEG@GO. Notably, the difference of the release rates at these pH values was most pronounced for the PEG-coated FMSNs, signifying the strong pH-responsive release behavior of Die molecules. Within the pH ranges (pH 4.5 – 7.4), double-layer-coated FMSNs exhibited the significantly delayed release rates as compared to coating-free and single-layer-coated analogs. Our nanocarriers demonstrated pH-sensitive controlled release of Die, suggesting as a smart drug delivery system for natural product-derived drugs.

In vitro correlation studies of antidiabetic, antioxidant activity and HPLC-ESI-MS/MS analysis of marine seaweeds from Gulf of Mannar

Marine seaweeds are known to exhibit potential biological activity, which possess a variety of biological functions. The important pharmacological aspect of using marine polyphenols as a strong natural antioxidant has been suggested to play a vital role in the alleviation of diabetes mellitus. The present study aims to investigate the antioxidant potential of four green marine seaweeds namely Chaetomorpha crassa, Caulerpa racemosa, Caulerpa verticillata and Caulerpa scalpelliformis in the management of Type 2 diabetes mellitus. In vitro evaluation of the antioxidant activity was assessed by employing ABTS, Phosphomolybdenum, and metal chelation activity methods. The results showed that among four marine seaweeds, the ethanolic extracts of C. verticillata have recorded the highest total flavonoid content (66.19 ± 0.002 mg QE/g) and antioxidant activity in ABTS (96.95 ± 0.411 %), Phosphomolybdenum assay (323.28±0.006μM), and Metal chelation activity (71.92 ± 0.48%). The IC50 values of C verticillata were found to be 0.42 mg/ml for ABTS and 0.78 mg/ml for Metal chelation activity respectively. Also, ethanolic extracts of C verticillata showed highly significant inhibition of α-amylase (70.64 ± 0.39% with IC50 of 0.420 mg/ml) and α-Glucosidase (64.07 ± 0.33% with IC50 of 0.068 mg/ml) in a dose-dependent manner. The resultant principal component analysis had showed the effective association between the antioxidant and antidiabetic potential of the marine seaweeds. It is clear, that C. verticillata could be a good choice to reduce the hyperglycemic condition by inhibiting the carbohydrate hydrolyzing enzymes and maintain tolerable oxidative stress.

Diphlorethohydroxycarmalol Isolated from Ishige okamurae Exerts Vasodilatory Effects via Calcium Signaling and PI3K/Akt/eNOS Pathway.

Nitric oxide (NO) is released by endothelial cells in the blood vessel wall to enhance vasodilation. Marine polyphenols are known to have protective effects against vascular dysfunction and hypertension. The present study is the first to investigate how diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae affects calcium levels, resulting in enhanced vasodilation. We examined calcium modulation with the well-known receptors, acetylcholine receptor (AchR) and vascular endothelial growth factor 2 (VEGFR2), which are related to NO formation, and further confirmed the vasodilatory effect of DPHC. We confirmed that DPHC stimulated NO production by increasing calcium levels and endothelial nitric oxide synthase (eNOS) expression. DPHC affected AchR and VEGFR2 expression, thereby influencing transient calcium intake. Specific antagonists, atropine and SU5416, were used to verify our findings. Furthermore, based on the results of in vivo experiments, we treated Tg(flk:EGFP) transgenic zebrafish with DPHC to confirm its vasodilatory effect. In conclusion, the present study showed that DPHC modulated calcium transit through AchR and VEGFR2, increasing endothelial-dependent NO production. Thus, DPHC, a natural marine component, can efficiently ameliorate cardiovascular diseases by improving vascular function.

Phenolic-Enriched Collagen Fibrillar Coatings on Titanium Alloy to Promote Osteogenic Differentiation and Reduce Inflammation.

The adsorption of biomolecules on biomaterial surfaces can promote their integration with surrounding tissue without changing their bulk properties. For biomaterials in bone reconstruction, the promotion of osteogenic differentiation and reduction of inflammation are desirable. Fibrillar coatings are interesting because of fibrils’ high surface area-volume ratio, aiding adsorption and adhesion. Fibrils also serve as a matrix for the immobilization of biomolecules with biological activity, such as the phenolic compound phloroglucinol (PG), the subunit of marine polyphenols. The aim of this work was to investigate the influence of PG coatings on fibroblast- and osteoblast-like cells to increase the osseointegration of titanium implants. Collagen fibril coatings, containing PG at low and high concentrations, were produced on titanium alloy (Ti6Al4V) scaffolds generated by additive manufacturing (AM). These coatings, especially PG-enriched coatings, reduced hydrophobicity and modulated the behavior of human osteosarcoma SaOS-2 and mouse embryonic fibroblast 3T3 cell lines. Both osteoblastic and fibroblastic cells spread and adhered well on PG-enriched coatings. Coatings significantly reduced the inflammatory response. Moreover, osteogenic differentiation was promoted by collagen coatings with a high PG concentration. Thus, the enrichment of collagen fibril coatings with PG is a promising strategy to improve Ti6Al4V implants for bone contact in orthopedics and dentistry and is worthy of further investigation.

해양 폴리페놀 복합음료 섭취가 역도선수들의 체간 근기능에 미치는 영향

해양 폴리페놀 복합음료 섭취가 역도선수들의 체간 근기능에 미치는 영향

Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor.

We had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABAA-benzodiazepine (BZD) receptor. Among the constituents of phlorotannin, dieckol is a major marine polyphenol from the brown alga Ecklonia cava. Although phlorotannins are known to exert hypnotic effects, the sleep-enhancing effect of dieckol has not yet been determined. We evaluated the effect of dieckol on sleep-wake state of mice by analyzing electroencephalograms (EEGs) and electromyograms. Flumazenil, a GABAA-BZD antagonist, was used to investigate the molecular mechanism underlying the effects of dieckol on sleep. The polygraphic recordings and corresponding hypnograms revealed that dieckol accelerated the initiation of non-rapid eye movement sleep (NREMS); it shortened sleep latency and increased NREMS duration. According to the change in time-course, dieckol showed sleep-enhancing effects by increasing the amount of NREMS and decreasing wakefulness during the same hours. Additionally, sleep quality was evaluated by analyzing the EEG power density, and dieckol was found to not affect sleep intensity while zolpidem was found to reduce it. Finally, we treated mice with zolpidem or dieckol in combination with flumazenil and found the latter to inhibit the sleep-enhancing effect of dieckol and zolpidem, thereby indicating that dieckol exerts sleep-enhancing effects by activating the GABAA-BZD receptor, similar to zolpidem. These results implied that dieckol can be used as a promising herbal sleep aid with minimal side effects, unlike the existing hypnotics.

Targeting acquired oncogenic burden in resilient pancreatic cancer: a novel benefit from marine polyphenols

The upsurge of marine-derived therapeutics for cancer treatment is evident, with many drugs in clinical use and in clinical trials. Seaweeds harbor large amounts of polyphenols and their anti-cancer benefit is linear to their anti-oxidant activity. Our studies identified three superlative anti-cancer seaweed polyphenol drug candidates (SW-PD). We investigated the acquisition of oncogenic burden in radiation-resilient pancreatic cancer (PC) that could drive tumor relapse, and elucidated the efficacy of SW-PD candidates as adjuvants in genetically diverse in vitro systems and a mouse model of radiation-residual disease. QPCR profiling of 88 oncogenes in therapy-resilient PC cells identified a 'shared' activation of 40 oncogenes. SW-PD pretreatment inflicted a significant mitigation of acquired (shared) oncogenic burden, in addition to drug- and cell-line-specific repression signatures. Tissue microarray with IHC of radiation-residual tumors in mice signified acquired cellular localization of key oncoproteins and other critical architects. Conversely, SW-PD treatment inhibited the acquisition of these critical drivers of tumor genesis, dissemination, and evolution. Heightened death of resilient PC cells with SW-PD treatment validated the translation aspects. The results defined the acquisition of oncogenic burden in resilient PC and demonstrated that the marine polyphenols effectively target the acquired oncogenic burden and could serve as adjuvant(s) for PC treatment.

Abstract 2074: Bioactive marine drugs target acquired oncogenic burden in resilient pancreatic cancer

Abstract The upsurge of marine-derived therapeutics for cancer treatment is evident, with many drugs in clinical use and in clinical trials. Seaweeds harbor large amounts of polyphenols and their anti-cancer benefit is linear to their anti-oxidant activity. Our studies identified three superlative anti-cancer seaweed polyphenol drug candidates (SW-PD). We investigated the acquisition of oncogenic burden in radiotherapy-resilient pancreatic cancer (PC) that could drive tumor relapse, and elucidated the efficacy of SW-PD candidates as adjuvants in genetically diverse in vitro systems (Panc-1, Panc-3.27, BxPC-3, MiaPaCa-2) and a mouse model of radiation-residual disease. For residual PC studies, PC xenografts developed in nude mice were selectively exposed to clinically relevant fractionated irradiation, (2 Gy/day for 5 days per week for a total of 3 weeks), to a total dose of 30 Gy. QPCR profiling of custom archived 88 oncogenes in therapy-resilient PC cells identified a ‘shared’ activation of 40 oncogenes. SW-PD pre-treatment inflicted a significant mitigation of acquired (shared) oncogenic burden, in addition to drug- and cell-line-specific repression signatures. Tissue-microarray with IHC of radiation-residual tumors in mice signified acquired cellular localization of key oncoproteins (Fosb, cFos, Fra2, cMYC, MYB, NF2) and other critical architects (SELE, CD73, Cytokeratins, Col3, Decorin, and Sulf2). Conversely, SW-PD treatment inhibited the acquisition of these critical drivers of tumor genesis, dissemination, and evolution. Heightened death of resilient PC cells with SW-PD treatment validated the translation aspects. The results defined the acquisition of oncogenic burden in resilient PC and demonstrated that the marine polyphenols effectively target the acquired oncogenic burden and could serve as adjuvant(s) for PC treatment. Citation Format: Sheeja Aravindan, Somasundaram T. Somasundaram, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan. Bioactive marine drugs target acquired oncogenic burden in resilient pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2074.

An assessment of temporal variation in the low molecular weight phlorotannin profiles in four intertidal brown macroalgae

Phlorotannins are a group of highly bioactive marine polyphenols found exclusively in brown algae (Phaeophyceae) where they play an integral role in chemical defence. Owing to their high degree of reactivity, phlorotannins have attracted recent commercial interest with potential for application in areas such as pharma-, nutra- and cosmeceuticals. However, to date, little is known regarding their biosynthesis and the factors that drive their natural variability, particularly in relation to their chemical properties such as polymerisation and isomerisation - two factors which directly influence their degree of activity. Low molecular weight (LMW; <3.5 kDa) phlorotannin-enriched fractions have exhibited a high level of antioxidant activity yet their degree of natural variability within macroalgae is not known. This study aimed to, for the first time, assess the temporal variation of LMW phlorotannin chemical profiles of four intertidal brown macroalgae dominant along the west coast of Ireland – Pelvetia canaliculata, Fucus vesiculosus, Ascophyllum nodosum and Himanthalia elongata. Samples were collected at six different time points over two years (2014–2015) and assessed for temporal shifts in the chemical profile, content and antioxidant activity. Species-specific profiles were detected, with each species displaying varying degrees of polymerisation and isomerisation, which were linked to the in vitro antioxidant activity observed. While some temporal shifts were observed in the molecular weight composition of the LMW phlorotannin profiles, they, along with the degree of isomerisation, did not appear to correspond with large-scale temporal changes in irradiance or temperature regime of Galway Bay. The results emphasise the strong degree of natural variability associated with phlorotannin profiles which, in situ, are likely to be influenced by several parameters synergistically; future studies should investigate small-scale effects of physio-chemical parameters, as well as biological factors, at microhabitat level, which could be aided by a laboratory-based assessment of individual parameters.

Ameliorative effect of dieckol-enriched extraction from Laminaria japonica on hepatic steatosis induced by a high-fat diet via β-oxidation pathway in ICR mice

An increasing number of studies indicate that dietary polyphenols are beneficial to non-alcoholic fatty liver (NAFL) disease. However, the published reports about marine polyphenols are still limited. In this work, the ameliorative effect of polyphenols from Laminaria (L.) japonica on NAFL was investigated in vivo. According to the spectral analyses, dieckol was identified from L. japonica. After NAFL was induced by a high-fat diet, the ICR mice were administered dieckol-enriched extract (DEE) (50 mg/kg/day) for 4 weeks. Compared with the normal diet (ND) group, significant (P < 0.05) improvements in body weight gain, liver index, visceral fat index, plasma lipid profiles, and hepatic fat deposition were observed in ND + DEE group. Moreover, DEE supplementation selectively ameliorated levels of phosphorylated-AMP-activated protein kinase, carnitine palmitoyltransferase-1, and peroxisome proliferator-activated receptor-α in liver. Therefore, polyphenols from L. japonica might have potential ameliorative effect on hepatic steatosis via stimulating hepatic fatty acid β-oxidation.

Physicochemical characterization and pharmacological evaluation of marine polyphenols from the brown algae Padina pavonica

Background and Aim: Natural products continue to be a primary resource in biomedicine and biotechnology. The marine environment is highly reserve for novel pharmaceutical and medical compounds. The aim of this work was to identify bioactive components from the brown seaweed Padina pavonica with specific pharmacological potential. Methods: In the present study, we investigated the efficacy of polyphenol fraction from Padina pavonica for in vivo anti-inflammatory activity using the carrageen an-induced paw edema model in rats and there in vitro antioxidant activity using two methods: DPPH radical scavenging assay and ferric reducing antioxidant power (FRAP) [8]. Results: The polyphenol-rich fraction from the brown seaweed Padina pavonica exhibits a significant anti-inflammatory activity at the dose of 100 and 200 mg/kg and the maximum reduction of the edema was observed at the third hour with 53.49% and 58.6% of inhibition, respectively. Along with, we were interested in the investigation of the antioxidant activity. The DPPH radical-scavenging assay shows that the polyphenol fractions have an interesting cavenging activity at a low concentration (0.25 mg/mL). In addition, the Ferric reducing antioxidant power (FRAP) method reveals an antioxidant activity with IC50 = 0.4 mg/mL. Conclusions: These findings indicate that the polyphenol fraction of Padina pavonica is a promising bio source of compounds with anti-inflammatory and antioxidant potential; this may be useful as a candidate for the developing of potential therapeutic products. Keywords: Brown Seaweeds; Padina pavonica; Anti-Inflammatory Activity; Antioxidant Activity

Triphlorethol A, a Dietary Polyphenol from Seaweed, Decreases Sleep Latency and Increases Non-Rapid Eye Movement Sleep in Mice.

In our previous studies, we have demonstrated that marine polyphenol phlorotannins promote sleep through the benzodiazepine site of the gamma-aminobutyric acid type A (GABAA) receptors. In this follow-up study, the sleep-promoting effects of triphlorethol A, one of the major phlorotannin constituents, were investigated. The effect of triphlorethol A on sleep-wake architecture and profiles was evaluated based on electroencephalogram and electromyogram data from C57BL/6N mice and compared with the well-known hypnotic drug zolpidem. Oral administration of triphlorethol A (5, 10, 25, and 50 mg/kg) dose-dependently decreased sleep latency and increased sleep duration during pentobarbital-induced sleep in imprinting control region mice. Triphlorethol A (50 mg/kg) significantly decreased sleep latency and increased the amount of non-rapid eye movement sleep (NREMS) in C57BL/6N mice, without affecting rapid eye movement sleep (REMS). There was no significant difference between the effects of triphlorethol A at 50 mg/kg and zolpidem at 10 mg/kg. Triphlorethol A had no effect on delta activity (0.5–4 Hz) of NREMS, whereas zolpidem significantly decreased it. These results not only support the sleep-promoting effects of marine polyphenol phlorotannins, but also suggest that the marine polyphenol compound triphlorethol A is a promising structure for developing novel sedative hypnotics.

Phlorotannin extracts from Fucales: Marine polyphenols as bioregulators engaged in inflammation-related mediators and enzymes

Phlorotannins are widely recognized as an inexhaustible family of naturally occurring molecules, with great potential in food and pharmaceutical industries. The present work explores the anti-inflammatory activity of phlorotannins from different Fucus species native from the Northern Atlantic coast, and from Fucus vesiculosus Linnaeus grown in an integrated multi-trophic aquaculture (IMTA) system, all scarcely studied regarding these compounds. Purified phlorotannin extracts were evaluated for their toxicity and anti-inflammatory potential in both cell (RAW 264.7 macrophages) and cell-free systems [lipoxygenase (LOX) inhibition and nitric oxide radical (NO) scavenging activity]. Phlorotannin content ranged between 110.28 and 288.36μgofphloroglucinol equivalents(PGE)/100mg dry purified extract (DE), wild species presenting higher content than those from IMTA. Regarding LOX, a strong correlation (r=−0.9118; p<0.0001) between the IC50 values and total phlorotannin content was found, Fucus guiryi G.I. Zardi, K.R. Nicastro, E.S. Serrão & G.A. Pearson exhibiting the best inhibitory capacity (IC50=82.10μg/mL), while F. vesiculosus from IMTA was the less effective (IC50>500μg/mL). Correlation was also observed for NO scavenging (r=−0.6363; p=0.0108). The anti-inflammatory capacity of phlorotannin extracts was further evaluated using RAW 264.7 macrophages stimulated with bacterial lipopolysaccharide, as model of inflammation. The extracts studied were not toxic at the tested concentrations (31.25–500μg/mL). F. vesiculosus from wild origin was the most effective in reducing NO in cell culture medium (IC25=56.52μg/mL), closely followed by other seaweed species under study. The IMTA species was the less effective one (IC25=317.41μg/mL). According to the results obtained, phlorotannin extracts from Fucales arise as potentially beneficial in inflammation-related conditions, effectively acting upon enzymatic and non-enzymatic inflammatory targets.

Do marine algal polyphenols have antidiabetic, antihyperlipidemic or anti-inflammatory effects in humans? A systematic review

ABSTRACTCardiovascular disease and type 2 diabetes are leading causes of morbidity and mortality globally. Marine algal polyphenols have potential to reduce the risk of these conditions, however, little is known about their impact in humans. This systematic review investigates the antidiabetic, antihyperlipidemic and anti-inflammatory effects of marine polyphenols in humans. Scopus, Medline, PsychInfo, Embase and Cochrane Library databases were searched in November 2016. Eligible studies included (1) human adults, (2) marine polyphenol intervention, (3) blood lipid, glucose, insulin or inflammatory marker outcomes, and (4) were a randomized-controlled trial. One postprandial cross-over trial and four parallel design trials were included involving 271 adults. Analysis across studies was performed using Cohen's d effect sizes. Supplementation with polyphenol-rich extracts had small-to-medium positive effects on fasting blood glucose, total cholesterol and LDL-cholesterol; however, there is inadequate evidence as yet to confirm if these are consistent effects. Further randomized-controlled trials should investigate polyphenols from Ecklonia cava and other macroalgal sources, to determine if there is a role for marine polyphenols in reducing the risk factors of chronic disease in humans.(PROSPERO registration number CRD42015016890)