Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

From Ocean to Medicine: Harnessing Seaweed's Potential for Drug Development.

Seaweed, a miscellaneous group of marine algae, has long been recognized for its rich nutritional composition and bioactive compounds, being considered nutraceutical ingredient. This revision delves into the promising role of seaweed-derived nutrients as a beneficial resource for drug discovery and innovative product development. Seaweeds are abundant sources of essential vitamins, minerals, polysaccharides, polyphenols, and unique secondary metabolites, which reveal a wide range of biological activities. These bioactive compounds possess potential therapeutic properties, making them intriguing candidates for drug leads in various medical applications and pharmaceutical drug development. It explores their pharmacological properties, including antioxidant, anti-inflammatory, antimicrobial, and anticancer activities, shedding light on their potential as therapeutic agents. Moreover, the manuscript provides insights into the development of formulation strategies and delivery systems to enhance the bioavailability and stability of seaweed-derived compounds. The manuscript also discusses the challenges and opportunities associated with the integration of seaweed-based nutrients into the pharmaceutical and nutraceutical industries. Regulatory considerations, sustainability, and scalability of sustainable seaweed sourcing and cultivation methods are addressed, emphasizing the need for a holistic approach in harnessing seaweed's potential. This revision underscores the immense potential of seaweed-derived compounds as a valuable reservoir for drug leads and product development. By bridging the gap between marine biology, pharmacology, and product formulation, this research contributes to the critical advancement of sustainable and innovative solutions in the pharmaceutical and nutraceutical sectors.

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.

Algae Food Products as a Healthcare Solution.

Diseases such as obesity; cardiovascular diseases such as high blood pressure, myocardial infarction and stroke; digestive diseases such as celiac disease; certain types of cancer and osteoporosis are related to food. On the other hand, as the world's population increases, the ability of the current food production system to produce food consistently is at risk. As a result, intensive agriculture has contributed to climate change and a major environmental impact. Research is, therefore, needed to find new sustainable food sources. One of the most promising sources of sustainable food raw materials is macroalgae. Algae are crucial to solving this nutritional deficiency because they are abundant in bioactive substances that have been shown to combat diseases such as hyperglycemia, diabetes, obesity, metabolic disorders, neurodegenerative diseases and cardiovascular diseases. Examples of these substances include polysaccharides such as alginate, fucoidan, agar and carrageenan; proteins such as phycobiliproteins; carotenoids such as ß-carotene and fucoxanthin; phenolic compounds; vitamins and minerals. Seaweed is already considered a nutraceutical food since it has higher protein values than legumes and soy and is, therefore, becoming increasingly common. On the other hand, compounds such as polysaccharides extracted from seaweed are already used in the food industry as thickening agents and stabilizers to improve the quality of the final product and to extend its shelf life; they have also demonstrated antidiabetic effects. Among the other bioactive compounds present in macroalgae, phenolic compounds, pigments, carotenoids and fatty acids stand out due to their different bioactive properties, such as antidiabetics, antimicrobials and antioxidants, which are important in the treatment or control of diseases such as diabetes, cholesterol, hyperglycemia and cardiovascular diseases. That said, there have already been some studies in which macroalgae (red, green and brown) have been incorporated into certain foods, but studies on gluten-free products are still scarce, as only the potential use of macroalgae for this type of product is considered. Considering the aforementioned issues, this review aims to analyze how macroalgae can be incorporated into foods or used as a food supplement, as well as to describe the bioactive compounds they contain, which have beneficial properties for human health. In this way, the potential of macroalgae-based products in eminent diseases, such as celiac disease, or in more common diseases, such as diabetes and cholesterol complications, can be seen.

Call the Eckols: Present and Future Potential Cancer Therapies.

In recent years, an increased interest in marine macroalgae bioactive compounds has been recorded due to their benefits to human health and welfare. Several of their bioactivities have been demonstrated, such as anti-inflammatory, antioxidant, anticarcinogenic, antibacterial and antiviral behavior. However, there still lacks a clear definition regarding how these compounds exert their bioactive properties. Of all the bioactive compounds derived from marine macroalgae, attention has been focused on phenolic compounds, specifically in phlorotannins, due to their potential for biomedical applications. Phlorotannins are a diverse and wide group of phenolic compounds, with several structural variations based on the monomer phloroglucinol. Among the diverse phlorotannin structures, the eckol-family of phlorotannins demonstrates remarkable bioactivity, notably their anti-tumoral properties. However, the molecular mechanisms by which this activity is achieved remain elusive and sparse. This review focuses on the described molecular mechanisms of anti-tumoral effects by the eckol family of compounds and the future prospects of these molecules for potential application in oncology therapies.

Fillet Fish Fortified with Algal Extracts of Codium tomentosum and Actinotrichia fragilis, as a Potential Antibacterial and Antioxidant Food Supplement.

With respect to the potential natural resources in the marine environment, marine macroalgae or seaweeds are recognized to have health impacts. Two marine algae that are found in the Red Sea, Codium tomentosum (Green algae) and Actinotrichia fragilis (Red algae), were collected. Antibacterial and antioxidant activities of aqueous extracts of these algae were evaluated in vitro. Polyphenols from the extracts were determined using HPLC. Fillet fish was fortified with these algal extracts in an attempt to improve its nutritional value, and sensory evaluation was performed. The antibacterial effect of C. tomentosum extract was found to be superior to that of A. fragilis extract. Total phenolic contents of C. tomentosum and A. fragilis aqueous extract were 32.28 ± 1.63 mg/g and 19.96 ± 1.28 mg/g, respectively, while total flavonoid contents were 4.54 ± 1.48 mg/g and 3.86 ± 1.02 mg/g, respectively. Extract of C. tomentosum demonstrates the highest antioxidant activity, with an IC50 value of 75.32 ± 0.07 µg/mL. The IC50 of L-ascorbic acid as a positive control was 22.71 ± 0.03 µg/mL. The IC50 values for inhibiting proliferation on normal PBMC cells were 33.7 ± 1.02 µg/mL and 51.0 ± 1.14 µg/mL for C. tomentosum and A. fragilis, respectively. The results indicated that both algal aqueous extracts were safe, with low toxicity to normal cells. Interestingly, fillet fish fortified with C. tomentosum extract demonstrated the greatest overall acceptance score. These findings highlight the potential of these seaweed species for cultivation as a sustainable and safe source of therapeutic compounds for treating human and fish diseases, as well as effective food supplements and preservatives instead of chemical ones after performing in vivo assays.

Chondracanthus teedei var. lusitanicus: The Nutraceutical Potential of an Unexploited Marine Resource.

Presently, there is a high demand for nutritionally enhanced foods, so it is a current challenge to look at new raw food sources that can supplement beneficially the human diet. The nutritional profile and key secondary metabolites of red seaweeds (Rhodophyta) are gaining interest because of this challenge. In this context, the possible use of the red seaweed Chondracanthus teedei var. lusitanicus (Gigartinales) as a novel nutraceutical source was investigated. As a result, we highlight the high mineral content of this seaweed, representing 29.35 g 100 g-1 of its dry weight (DW). Despite the low levels of calcium and phosphorus (0.26 and 0.20 g 100 g-1 DW, respectively), this seaweed is an interesting source of nitrogen and potassium (2.13 and 2.29 g-1 DW, accordingly). Furthermore, the high content of carbohydrates (56.03 g 100 g-1 DW), which acts as dietary fibers, confers a low caloric content of this raw food source. Thus, this study demonstrates that C. teedei var. lusitanicus is in fact an unexploited potential resource with the capability to provide key minerals to the human diet with promising nutraceutical properties.

On the Health Benefits vs. Risks of Seaweeds and Their Constituents: The Curious Case of the Polymer Paradigm.

To exploit the nutraceutical and biomedical potential of selected seaweed-derived polymers in an economically viable way, it is necessary to analyze and understand their quality and yield fluctuations throughout the seasons. In this study, the seasonal polysaccharide yield and respective quality were evaluated in three selected seaweeds, namely the agarophyte Gracilaria gracilis, the carrageenophyte Calliblepharis jubata (both red seaweeds) and the alginophyte Sargassum muticum (brown seaweed). It was found that the agar synthesis of G. gracilis did not significantly differ with the seasons (27.04% seaweed dry weight (DW)). In contrast, the carrageenan content in C. jubata varied seasonally, being synthesized in higher concentrations during the summer (18.73% DW). Meanwhile, the alginate synthesis of S. muticum exhibited a higher concentration (36.88% DW) during the winter. Therefore, there is a need to assess the threshold at which seaweed-derived polymers may have positive effects or negative impacts on human nutrition. Furthermore, this study highlights the three polymers, along with their known thresholds, at which they can have positive and/or negative health impacts. Such knowledge is key to recognizing the paradigm governing their successful deployment and related beneficial applications in humans.

Environmental Impact on Seaweed Phenolic Production and Activity: An Important Step for Compound Exploitation.

Seaweeds are a potential source of bioactive compounds that are useful for biotechnological applications and can be employed in different industrial areas in order to replace synthetic compounds with components of natural origin. Diverse studies demonstrate that there is a solid ground for the exploitation of seaweed bioactive compounds in order to prevent illness and to ensure a better and healthier lifestyle. Among the bioactive algal molecules, phenolic compounds are produced as secondary metabolites with beneficial effects on plants, and also on human beings and animals, due to their inherent bioactive properties, which exert antioxidant, antiviral, and antimicrobial activities. The use of phenolic compounds in pharmaceutical, nutraceutical, cosmetics, and food industries may provide outcomes that could enhance human health. Through the production of healthy foods and natural drugs, bioactive compounds from seaweeds can help with the treatment of human diseases. This review aims to highlight the importance of phenolic compounds from seaweeds, the scope of their production in nature and the impact that these compounds can have on human and animal health through nutraceutical and pharmaceutical products.

Invasive Seaweeds in the Iberian Peninsula: A Contribution for Food Supply.

The introduction of exotic organisms in marine ecosystems can lead to economic and ecological losses. Globally, seaweeds represent a significant part of these non-indigenous species (NIS), with 407 introduced algal species. Furthermore, the presence of NIS seaweeds has been reported as a major concern worldwide since the patterns of their potential invasion mechanisms and vectors are not yet fully understood. Currently, in the Iberian Peninsula, around 50 NIS seaweeds have been recorded. Some of these are also considered invasive due to their overgrowth characteristic and competition with other species. However, invasive seaweeds are suitable for industrial applications due to their high feedstock. Hence, seaweeds' historical use in daily food diet, allied to research findings, showed that macroalgae are a source of nutrients and bioactive compounds with nutraceutical properties. The main goal of this review is to evaluate the records of NIS seaweeds in the Iberian Peninsula and critically analyze the potential of invasive seaweeds application in the food industry.

Antitumour Potential of Gigartina pistillata Carrageenans against Colorectal Cancer Stem Cell-Enriched Tumourspheres.

Gigartina pistillata is a red seaweed common in Figueira da Foz, Portugal. Here, the antitumour potential of G. pistillata carrageenan, with a known variable of the life cycle, the female gametophyte (FG) and tetrasporophyte (T) was evaluated against colorectal cancer stem cell (CSC) -enriched tumourspheres. FTIR-ATR analysis of G. pistillata carrageenan extracts indicated differences between life cycle phases, being FG a κ/ι hybrid carrageenan and T a ʎ/ξ hybrid. Both carrageenan extracts presented IC50 values inferior to 1 µg/mL in HT29-derived CSC-enriched tumourspheres, as well as reduced tumoursphere area. The two extracts were also effective at reducing cellular viability in SW620- and SW480-derived tumourspheres. These results indicate that carrageenans extracted from two G. pistillata life cycle phases have antitumour potential against colorectal cancer stem-like cells, specially the T carrageenan.

Seaweed Phenolics: From Extraction to Applications.

Seaweeds have attracted high interest in recent years due to their chemical and bioactive properties to find new molecules with valuable applications for humankind. Phenolic compounds are the group of metabolites with the most structural variation and the highest content in seaweeds. The most researched seaweed polyphenol class is the phlorotannins, which are specifically synthesized by brown seaweeds, but there are other polyphenolic compounds, such as bromophenols, flavonoids, phenolic terpenoids, and mycosporine-like amino acids. The compounds already discovered and characterized demonstrate a full range of bioactivities and potential future applications in various industrial sectors. This review focuses on the extraction, purification, and future applications of seaweed phenolic compounds based on the bioactive properties described in the literature. It also intends to provide a comprehensive insight into the phenolic compounds in seaweed.

Effect of Carrageenans on Vegetable Jelly in Humans with Hypercholesterolemia.

Changes in lipid profile constitute the main risk factor for cardiovascular diseases. Algae extracted carrageenans are long-chain polysaccharides and their ability to form gels provides for the formation of vegetable jelly. The objective was to evaluate the bioactive potential of carrageenan (E407) in the lipid profile, after ingestion of jelly. A total of 30 volunteers of both sexes, aged 20-64 years and with total cholesterol (TC) values ≥200 mg/dL, who ingested 100 mL/day of jelly for 60 days, were studied. All had two venous blood collections: before starting the jelly intake and after 60 days. At both times, TC, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG), were evaluated using commercial kits and spectrophotometer. The statistics were performed using the SPSS 25.0 software and p < 0.05 were considered statistically significant. Serum values after 60 days of jelly intake revealed a statistically significant decrease in TC levels (5.3%; p = 0.001) and LDL-C concentration (5.4%; p = 0.048) in females. The daily intake of vegetable jelly for 60 days showed a reduction in serum TC and LDL-C levels in women, allowing us to conclude that carrageenan has bioactive potential in reducing TC concentration.

Seaweed Proteins: A Step towards Sustainability?

This review delves into the burgeoning field of seaweed proteins as promising alternative sources of protein. With global demand escalating and concerns over traditional protein sources' sustainability and ethics, seaweed emerges as a viable solution, offering a high protein content and minimal environmental impacts. Exploring the nutritional composition, extraction methods, functional properties, and potential health benefits of seaweed proteins, this review provides a comprehensive understanding. Seaweed contains essential amino acids, vitamins, minerals, and antioxidants. Its protein content ranges from 11% to 32% of dry weight, making it valuable for diverse dietary preferences, including vegetarian and vegan diets. Furthermore, this review underscores the sustainability and environmental advantages of seaweed protein production compared to traditional sources. Seaweed cultivation requires minimal resources, mitigating environmental issues like ocean acidification. As the review delves into specific seaweed types, extraction methodologies, and functional properties, it highlights the versatility of seaweed proteins in various food products, including plant-based meats, dairy alternatives, and nutritional supplements. Additionally, it discusses the potential health benefits associated with seaweed proteins, such as their unique amino acid profile and bioactive compounds. Overall, this review aims to provide insights into seaweed proteins' potential applications and their role in addressing global protein needs sustainably.

Antioxidant and Antidiabetic Activity of Algae.

Currently, algae arouse a growing interest in the pharmaceutical and cosmetic area due to the fact that they have a great diversity of bioactive compounds with the potential for pharmacological and nutraceutical applications. Due to lifestyle modifications brought on by rapid urbanization, diabetes mellitus, a metabolic illness, is the third largest cause of death globally. The hunt for an efficient natural-based antidiabetic therapy is crucial to battling diabetes and the associated consequences due to the unfavorable side effects of currently available antidiabetic medications. Finding the possible advantages of algae for the control of diabetes is crucial for the creation of natural drugs. Many of algae's metabolic processes produce bioactive secondary metabolites, which give algae their diverse chemical and biological features. Numerous studies have demonstrated the antioxidant and antidiabetic benefits of algae, mostly by blocking carbohydrate hydrolyzing enzyme activity, such as α-amylase and α-glucosidase. Additionally, bioactive components from algae can lessen diabetic symptoms in vivo. Therefore, the current review concentrates on the role of various secondary bioactive substances found naturally in algae and their potential as antioxidants and antidiabetic materials, as well as the urgent need to apply these substances in the pharmaceutical industry.

Modified Atmosphere Packaging (MAP) for Seaweed Conservation: Impact on Physicochemical Characteristics and Microbiological Activity.

Conventional conservation techniques such as drying, salting or freezing do not allow for preserving the original characteristics of seaweeds. The present work aims to study the impact of minimal processing, in particular "Modified Atmosphere Packaging" (MAP), on the physicochemical characteristics and food safety of two seaweed species, "laver" (Porphyra umbilicalis) and "sea-lettuce" (Ulva lactuca), stored at 6 °C for 15 days. Different parameters were evaluated using analytical methods, namely the composition of headspace gases, color, texture, microorganisms, and volatile organic compounds (VOCs). The main findings of this study were that the MAP treatment was able to inhibit the respiration rate of minimally processed seaweeds, also preserving their color and texture. There was a remarkable reduction in the microbial load for P. umbilicalis treated under modified and vacuum atmospheres, and U. lactuca exhibited relatively steady values with no notable differences between the treatments and the control. Therefore, during the 15-day study period, both seaweeds met the requirements for food safety. GC-TOF-MS allowed to conclude that both MAP and vacuum treatments were more efficient in maintaining the odor characteristics of U. lactuca compared to P. umbilicalis with no significant differences throughout the storage days. Metabolic responses to diverse sources of abiotic stress seemed to account for most of the changes observed.

Seaweeds' pigments and phenolic compounds with antimicrobial potential.

Recently, there has been increased interest in the development of novel antimicrobial compounds for utilization in a variety of sectors, including pharmaceutical, biomedical, textile, and food. The use, overuse, and misuse of synthetic compounds or derivatives have led to an increase of pathogenic microorganisms gaining resistance to the traditional antimicrobial therapies, which has led to an increased need for alternative therapeutic strategies. Seaweed are marine organisms that can be cultivated sustainably, and they are a source of polar molecules, such as pigments and phenolic compounds, which demonstrated antimicrobial potential. This review focuses on current knowledge about pigments and phenolic compounds isolated from seaweeds, their chemical characteristics, antimicrobial bioactivity, and corresponding mechanism of action.

Marine macroalgae in a circular economy context: A comprehensive analysis focused on residual biomass.

The accumulation of Marine Macroalgal Waste (MMW) - drifted marine macroalgae - is a growing phenomenon. The lack of appropriate management protocols for this residual biomass leaves it mostly unmanaged or disposed of in landfills. Such inappropriate solutions lead to negative environmental impacts, health concerns and coastal degradation, representing an opportunity to develop the bioeconomy. Although a relevant number of studies exists on the use of edible marine macroalgae for several purposes, there is generally a lack of information concerning MMW valorisation, at both local and global scales. This review thus explores the ecological and biotechnological potential for the establishment of a new approach for MMW valorisation based in the circular and blue economies. It is supported in literature on the use of residual biomass whenever possible and also includes studies with fresh biomass to extrapolate, considering known characteristics of MMW; consequently, a roadmap for its utilisation is provided. The review includes characteristics of various seaweeds, MMW accumulation worldwide and traditional uses, together with the development of alternative and integrated valorisation strategies. By analysing a large number of studies, it was possible to perceive a clear potential to explore MMW to obtain renewable fuels, especially biogas and bioethanol and for use in agricultural activities. Allied to this, the extraction of value-added compounds, such as lipids, pigments, phenolic compounds and specific polysaccharides is highlighted, aiming to contribute to the development of an economically feasible zero-waste biorefinery approach.

Marine macroalgae as a feasible and complete resource to address and promote Sustainable Development Goals (SDGs).

Because the world's population is increasing, science-based policies are needed to promote sustainable global development. It is important to maintain and restore the environment and help human society overcome the risks from industrialization and unsustainable exponential growth. In recent years, many studies have highlighted that macroalgae represent a key marine resource for ecological and sustainable living, thus helping to address today's global problems, such as water pollution, ocean acidification, and global warming. Macroalgae show the potential to provide innovative, ecofriendly, and nutritious food sources and natural compounds for various industries, such as biomedical, food, agricultural, and pharmaceutical industries. This review discusses how macroalgae can help us today and how they can promote a more sustainable way of life in the future. It also discusses the potential danger for ecosystems and the global population if these organisms are not part of the solution but part of the problem. Integr Environ Assess Manag 2022;18:1148-1161. © 2022 SETAC.

Seaweeds as Valuable Sources of Essential Fatty Acids for Human Nutrition.

The overexploitation of terrestrial habitats, combined with the ever-growing demand for food, has led to the search for alternative food sources. The importance of seaweeds as food sources has been growing, and their potential as sources of fatty acids (FA) make seaweeds an interesting feedstock for the food and nutraceutical industries. The aim of this study is to assess the potential of five red seaweeds (Asparagospis armata, Calliblepharis jubata, Chondracanthus teedei var. lusitanicus, Gracilaria gracilis, and Grateloupia turuturu) and three brown seaweeds (Colpomenia peregrina, Sargassum muticum and Undaria pinnatifida), harvested in central Portugal, as effective sources of essential FA for food or as dietary supplements. FA were extracted from the biomass, transmethylated to methyl esters, and analyzed through gas chromatography-mass spectrometry. G. gracilis presented the highest content of saturated fatty acids (SFA) (41.49 mg·g-1), whereas C. jubata exhibited the highest content of highly unsaturated fatty acids (HUFA) (28.56 mg·g-1); the three G. turuturu life cycle stages presented prominent SFA and HUFA contents. Omega-6/omega-3 ratios were assessed and, in combination with PUFA+HUFA/SFA ratios, it is suggested that C. jubata and U. pinnatifida may be the algae with highest nutraceutical potential, promoting health benefits and contributing to a balanced dietary intake of fatty acids.