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.

Omega-3 enriched chick diet reduces the foraging areas of breeders in two closely related shearwaters from contrasting marine environments.

Seabirds have evolved several life-history characteristics to help buffer environmental stochasticity. However, particularly during the breeding season, seabirds may be affected by reductions in prey availability and localised oceanographic conditions caused by variations in the environment. The increase in sea surface temperature, triggered by accelerated global warming, is impairing phytoplankton production of omega-3 fatty acids (FAs). Here, we assessed the ecological role of omega-3 FAs on chick development and subsequently on breeder foraging behaviour in two closely related shearwater species foraging in contrasting marine environments. We supplemented chicks with omega-3 FA pills or with control placebo pills and monitored chick growth, chick health status and breeder at-sea foraging behaviour using global positioning system devices. We found that omega-3 chick supplementation reduced the 95% kernel utilization distribution of short trips of Cape Verde shearwaters, but overall, breeders kept a similar foraging pattern between treatments, potentially influenced by predictable prey patches off the West African coast. In contrast, for Cory's shearwaters, the parents of the omega-3 group greatly reduced the foraging effort. This suggests that the proximity to productive prey patches around the colony may help birds to adjust their effort and, therefore, energy expenditure, to changes in the development of their offspring, as driven by their nutritional status. Overall, our results suggest a link between a chick diet enriched in omega-3 FAs and parental foraging effort, providing insight into their ability to cope with a changing and increasingly stochastic marine environment.

Algal Phycocolloids: Bioactivities and Pharmaceutical Applications.

Seaweeds are abundant sources of diverse bioactive compounds with various properties and mechanisms of action. These compounds offer protective effects, high nutritional value, and numerous health benefits. Seaweeds are versatile natural sources of metabolites applicable in the production of healthy food, pharmaceuticals, cosmetics, and fertilizers. Their biological compounds make them promising sources for biotechnological applications. In nature, hydrocolloids are substances which form a gel in the presence of water. They are employed as gelling agents in food, coatings and dressings in pharmaceuticals, stabilizers in biotechnology, and ingredients in cosmetics. Seaweed hydrocolloids are identified in carrageenan, alginate, and agar. Carrageenan has gained significant attention in pharmaceutical formulations and exhibits diverse pharmaceutical properties. Incorporating carrageenan and natural polymers such as chitosan, starch, cellulose, chitin, and alginate. It holds promise for creating biodegradable materials with biomedical applications. Alginate, a natural polysaccharide, is highly valued for wound dressings due to its unique characteristics, including low toxicity, biodegradability, hydrogel formation, prevention of bacterial infections, and maintenance of a moist environment. Agar is widely used in the biomedical field. This review focuses on analysing the therapeutic applications of carrageenan, alginate, and agar based on research highlighting their potential in developing innovative drug delivery systems using seaweed phycocolloids.

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.

An Overview on Antimicrobial Potential of Edible Terrestrial Plants and Marine Macroalgae Rhodophyta and Chlorophyta Extracts.

Antibiotics are used to prevent and treat bacterial infections. After a prolonged use of antibiotics, it may happen that bacteria adapt to their presence, developing antibiotic resistance and bringing up health complications. Nowadays, antibiotic resistance is one of the biggest threats to global health and food security; therefore, scientists have been searching for new classes of antibiotic compounds which naturally express antimicrobial activity. In recent decades, research has been focused on the extraction of plant compounds to treat microbial infections. Plants are potential sources of biological compounds that express several biological functions beneficial for our organism, including antimicrobial activity. The high variety of compounds of natural origin makes it possible to have a great bioavailability of antibacterial molecules to prevent different infections. The antimicrobial activity of marine plants, also called seaweeds or macroalgae, for both Gram-positive and Gram-negative, and several other strains infective for humans, has been proven. The present review presents research focused on the extraction of antimicrobial compounds from red and green macroalgae (domain Eukarya, kingdom Plantae). Nevertheless, further research is needed to verify the action of macroalgae compounds against bacteria in vitro and in vivo, to be involved in the production of safe and novel antibiotics.

Antiviral Activity and Mechanisms of Seaweeds Bioactive Compounds on Enveloped Viruses-A Review.

In the last decades, the interest in seaweed has significantly increased. Bioactive compounds from seaweed's currently receive major attention from pharmaceutical companies as they express several interesting biological activities which are beneficial for humans. The structural diversity of seaweed metabolites provides diverse biological activities which are expressed through diverse mechanisms of actions. This review mainly focuses on the antiviral activity of seaweed's extracts, highlighting the mechanisms of actions of some seaweed molecules against infection caused by different types of enveloped viruses: influenza, Lentivirus (HIV-1), Herpes viruses, and coronaviruses. Seaweed metabolites with antiviral properties can act trough different pathways by increasing the host's defense system or through targeting and blocking virus replication before it enters host cells. Several studies have already established the large antiviral spectrum of seaweed's bioactive compounds. Throughout this review, antiviral mechanisms and medical applications of seaweed's bioactive compounds are analyzed, suggesting seaweed's potential source of antiviral compounds for the formulation of novel and natural antiviral drugs.

An Overview of Potential Seaweed-Derived Bioactive Compounds for Pharmaceutical Applications.

Nowadays, seaweeds are widely involved in biotechnological applications. Due to the variety of bioactive compounds in their composition, species of phylum Ochrophyta, class Phaeophyceae, phylum Rhodophyta and Chlorophyta are valuable for the food, cosmetic, pharmaceutical and nutraceutical industries. Seaweeds have been consumed as whole food since ancient times and used to treat several diseases, even though the mechanisms of action were unknown. During the last decades, research has demonstrated that those unique compounds express beneficial properties for human health. Each compound has peculiar properties (e.g., antioxidant, antimicrobial, antiviral activities, etc.) that can be exploited to enhance human health. Seaweed's extracted polysaccharides are already involved in the pharmaceutical industry, with the aim of replacing synthetic compounds with components of natural origin. This review aims at a better understanding of the recent uses of algae in drug development, with the scope of replacing synthetic compounds and the multiple biotechnological applications that make up seaweed's potential in industrial companies. Further research is needed to better understand the mechanisms of action of seaweed's compounds and to embrace the use of seaweeds in pharmaceutical companies and other applications, with the final scope being to produce sustainable and healthier products.

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.

An Overview to the Health Benefits of Seaweeds Consumption.

Currently, seaweeds are gaining major attention due to the benefits they give to our health. Recent studies demonstrate the high nutritional value of seaweeds and the powerful properties that seaweeds' bioactive compounds provide. Species of class Phaeophyceae, phylum Rhodophyta and Chlorophyta possess unique compounds with several properties that are potential allies of our health, which make them valuable compounds to be involved in biotechnological applications. In this review, the health benefits given by consumption of seaweeds as whole food or by assumption of bioactive compounds trough natural drugs are highlighted. The use of seaweeds in agriculture is also highlighted, as they assure soils and crops free from chemicals; thus, it is advantageous for our health. The addition of seaweed extracts in food, nutraceutical, pharmaceutical and industrial companies will enhance the production and consumption/usage of seaweed-based products. Therefore, there is the need to implement the research on seaweeds, with the aim to identify more bioactive compounds, which may assure benefits to human and animal health.

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.

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.

Diverse Applications of Marine Macroalgae.

The aim of this paper is to review the multiplicity of the current uses of marine macroalgae. Seaweeds are already used in many products and for different purposes, from food products to medicine. They are a natural resource that can provide a number of compounds with beneficial bioactivities like antioxidant, anti-inflammatory, anti-aging effects, among others. Despite studies directed in prospecting for their properties and the commodities already marketed, they could, surely, be even more researched and sustainably explored.

Impacts of S-metolachlor and terbuthylazine in fatty acid and carbohydrate composition of the benthic clam Scrobicularia plana.

S-metolachlor (SMOC) and terbuthylazine (TBA) are herbicides that commonly appear as active ingredients (a.i.) in the composition of plant protection products. In a previous work, experimental bioassays were performed using those chemicals to find suitable molecular biomarkers to assess its toxicity to the non-target species Scrobicularia plana. The results obtained showed that the pollutants produce mortality and biochemical changes at the species, namely in protein contents and enzymatic activity levels. Thus, for a better understanding of the total biochemical impacts of those pollutants in S. plana, the composition of fatty acids (FA) and carbohydrates (CH) of the survival organisms are investigated here. In addition, since this species is edible its biochemical profile is directly related to its nutritious quality, which is analysed in this study. Furthermore, the analyses were performed in two types of tissue - the muscle and visceral mass of each survival organism. The greatest changes in FA composition are observable in small size class, being the most sensitive size class both at the toxicological and biochemical level. FA contents are higher in small organisms, both at the field and under laboratory conditions, being the disparity between size classes higher in visceral masses than in muscles. Indeed, muscles adequately represent the FA profile since those molecules appear in higher content in this tissue compared to visceral masses, becoming the better indicator tissue of biochemical changes. Besides, using muscles, less amount of biomass is needed, so it turns out to be the most cost-effective tissue to be used as endpoint in future studies. FA profiles observed at SMOC and TBA exposure are different, organisms from TBA exposure presenting a lower nutritious quality, in terms of FA abundance and diversity, than the organisms exposed to SMOC. Still, SMOC produces reductions of HUFA, essential fatty acids that cannot be synthesized by the species. Moreover, HUFA (mostly EPA and DHA) occupied the greatest part of the FA composition of organisms exposed to the control treatments and to TBA; however, the decreases of HUFA caused by the SMOC exposure change the profiles and make SFA the most dominant group. These findings represent a risk of low occurrence of essential fatty acids in entire aquatic environments exposed to the chemicals studied. Regarding CH, glucose is the only monosaccharide found in S. plana which was expected since glycogen is the main polysaccharide in animal tissues. In general, the glucose content increases with a concentration of pollutants, whereas the glycogen concentration decreases, suggesting that the glucose is being released as a response to chemical stress. Thus, this work presents tools to assess biochemical impacts of S-metolachlor and terbuthylazine in aquatic systems and to goes deeper in the knowledge of these pollutants' toxicity to non-target species to predict its propagation through aquatic trophic webs.

Effects of a herbicide and copper mixture on the quality of marine plankton.

Pesticides and metals are often used in agriculture and are therefore often simultaneously discharged to nearby estuarine and marine areas. The effects of this organic-inorganic chemical mixture on food quality of aquatic organisms are currently unknown. In this study we test if a mixture of copper (inorganic) and the herbicide Primextra® Gold TZ (organic) affects the quality of the diatom Thalassiosira weissflogii and the copepod Acartia tonsa - two key species that fuel the local food-web. We quantified quality (i.e. energy content as food for the next trophic level) in terms of fatty acids, proteins and thiobarbituric acid reacting substances. We found non-additive effects (positive and negative) of the metal-herbicide mixture on the diatom and copepod species. In general, nutritionally important biochemical parameters of Acartia tonsa were most sensitive to the chemical stressors.

The antagonist and synergist potential of cholinium-based deep eutectic solvents.

The design of environmentally friendlier solvents has gained increasing relevance in the last decade. Deep eutectic solvents (DES) have recently emerged, with advantages like low-cost and putative lower environmental impact. However, information about DES toxicity is still scarce. This work aims to contribute to profiling the ecotoxicity of DES based on cholinium chloride ([Chol]Cl). Six DES were addressed, combining [Chol]Cl (as hydrogen bond acceptor - HBA) with ethylene glycol, glycerol, 1,2-propanediol, propionic acid, 1-propanol, and urea as hydrogen bond donors (HBD), in different molar ratios. The Microtox® Acute Toxicity Test, was used for assessing their toxicity towards the marine bacteria Allivibrio fischeri . Because the dissociation of DES in water is expected, analysis appraising the mixtures toxicity theory should be considered, which is a step forward in this field. This analysis suggested that [Chol]Cl and all HBD with the exception of propionic acid:[Chol]Cl 1:2 and 4:1 behave antagonistically, which is contrary to what has been suggested previously. The most extreme cases are Urea:[Chol]Cl and 1-Propanol:[Chol]Cl, with EC50 values higher than their starting materials dosed singly, configuring very promising and biocompatible alternative solvents. Toxicity was found to be dependent on DES composition, as well as on molar proportions of the starting materials.

Ecotoxicity analysis of cholinium-based ionic liquids to Vibrio fischeri marine bacteria.

Cholinium-based ionic liquids are quaternary ammonium salts with a wide range of potential industrial applications. Based on the fact that the cholinium is a complex B vitamin and widely used as food additive, the cholinium-based ionic liquids are generically regarded as environmentally "harmless" and thus, accepted as "non-toxic", although their ecotoxicological profile is poorly known. This work provides new ecotoxicological data for ten cholinium-based salts and ionic liquids, aiming to extend the surprisingly restricted body of knowledge about the ecotoxicity of this particular family and to gain insight on the toxicity mechanism of these compounds. The results reported here show that not all the cholinium tested can be considered harmless towards the test organism adopted. Moreover, the results suggest that the cholinium family exhibits a different mechanism of toxicity as compared to the imidazolium ionic liquids previously described in the literature.

Sustainable design for environment-friendly mono and dicationic cholinium-based ionic liquids.

Cholinium-based ionic liquids are receiving crescent interest in diverse areas of application given their biological compatibility and potential for industrial application. In this work, mono and dicationic cholinium ionic liquids as well as cholinium derivatives were synthesized and their toxicity assessed using the luminescent bacteria Vibrio fischeri. A range of cholinium derivatives was synthesized, using different amines and the correspondent brominated derivatives, through the alkylation of the amine with the halide in MeCN. The results indicate that their toxicity is highly dependent on the structural modifications of the cholinium cation, mainly related to the alkyl side or linkage chain length, number of hydroxyethyl groups and insertion of carbon-carbon multiple bonds. The data indicated that it is possible to perform environmentally advantageous structural alterations, namely the addition of double bonds, which would not negatively affect V. fischeri. Moreover, the dicationic compounds revealed a significantly lower toxicity than the monocationic counterparts. The picture emerging from the results supports the idea that cholinium derivatives are promising ionic liquids with a low environmental impact, emphasizing the importance of a careful and directed design of ionic liquid structures.

Toxicity of two pesticides in binary mixture on survival and enzymatic response of Cerastoderma edule - The warming influence.

Pesticide application increased by about 1 million tonnes in the last 3 decades. Pesticides' overuse, coupled with the need for several pesticides to control different pests in the same crop, and its application many times per year, results in dangerous chemical cocktails that enter in aquatic systems, with impacts to the ecosystems and its communities. Climatic changes are currently another great concern, is predicted by the end of the 21st century, the earth's surface temperature will increase by about 4 °C. Bivalve species are reported as essential to the ecosystems' balance. However, they are also indicated as the organisms that will suffer the most serious effects of the temperature increase. So, this work intends to: a) verify the harm of the sub-lethal concentrations of two worldwide used pesticides, oxyfluorfen and copper (Cu), when combined, to Cerastoderma edule at 15 °C and 20 °C; b) assess the changes in the antioxidant defence system, the activity of the neurological enzyme acetylcholinesterase and the nutritive value of C. edule, after exposure to sub-lethal concentrations of oxyfluorfen and Cu, single and in the mixture, at 15 °C and 20 °C; c) observe the interaction between Cu and oxyfluorfen, considering the different biomarkers. Bivalves were exposed to oxyfluorfen and Cu, single and combined, for 96 h, at 15 °C and 20 °C. Results showed lethal effects to the organisms exposed at 20 °C when exposed to the highest binary mixture concentrations. Biochemical effects were observed on the organisms exposed to 15 °C, despite not observing any lethal effects. Briefly, there was a reported increase in oxidative stress and a decrease in protein content, regardless of the increase in the activity of antioxidant enzymes. These results suggest the potentially dangerous effects of the chemicals' mixture combined with the temperature, on this species and its consumers, impacting the trophic chain, and consequently, the community structure and function.

Designing ionic liquids: the chemical structure role in the toxicity.

Ionic liquids (ILs) are a novel class of solvents with interesting physicochemical properties. Many different applications have been reported for ILs as alternatives to organic solvents in chemical and bioprocesses. Despite the argued advantage of having low vapor pressure, even the most hydrophobic ILs show some degree of solubility in water, allowing their dispersion into aquatic systems and raising concerns on its pollutant potential. Moreover, nowadays most widespread notion concerning the ILs toxicity is that there is a direct relationship with their hydrophobicity/lipophilicity. This work aims at enlarging the currently limited knowledge on ILs toxicity by addressing negative impacts in aquatic ecosystems and investigating the possibility of designing hydrophobic ILs of low ecotoxicity, by the manipulation of their chemical structures. The impact of aromaticity on the toxicity of different cations (pyridinium, piperidinium, pyrrolidinium and imidazolium) and hydrophobic anions (bis(trifluoromethylsulfonyl)imide [NTf(2)] and hexafluorophosphate [PF(6)]) was analysed. Concomitantly, several imidazolium-based ILs of the type [C( n )C( m )C( j )im][NTf(2)] were also studied to evaluate the effects of the position of the alkyl chain on the ILs' toxicity. For that purpose, standard assays were performed using organisms of different trophic levels, Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna, allowing to evaluate the consistency of the structure-activity relationships across different biological targets. The results here reported suggest the possibility of designing ILs with an enhanced hydrophobic character and lower toxicity, by elimination of their aromatic nature.