Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

The Potential of Algae in the Nutricosmetic Sector.

Seaweeds or algae are marine autotrophic organisms. They produce nutrients (e.g., proteins, carbohydrates, etc.) essential for the survival of living organisms as they participate in biochemical processes and non-nutritive molecules (such as dietary fibers and secondary metabolites), which can improve their physiological functions. Seaweed polysaccharides, fatty acids, peptides, terpenoids, pigments, and polyphenols have biological properties that can be used to develop food supplements and nutricosmetic products as they can act as antibacterial, antiviral, antioxidant, and anti-inflammatory compounds. This review examines the (primary and secondary) metabolites produced by algae, the most recent evidence of their effect on human health conditions, with particular attention to what concerns the skin and hair's well-being. It also evaluates the industrial potential of recovering these metabolites from biomass produced by algae used to clean wastewater. The results demonstrate that algae can be considered a natural source of bioactive molecules for well-being formulations. The primary and secondary metabolites' upcycling can be an exciting opportunity to safeguard the planet (promoting a circular economy) and, at the same time, obtain low-cost bioactive molecules for the food, cosmetic, and pharmaceutical industries from low-cost, raw, and renewable materials. Today's lack of methodologies for recovering bioactive molecules in large-scale processes limits practical realization.

A concise review on marine bromopyrrole alkaloids as anticancer agents.

Natural products have been the most important sources of chemically diverse raw materials that have inspired pharmaceutical discoveries over the past few decades. Many pharmaceutical companies are utilizing plant extracts to develop relatively crude therapeutic formulations. The interesting chemicals identified as natural products are derived from the phenomenon of biodiversity, where the interactions between the organisms and their environment formulate the diverse and complex chemical entities within them that enhance their survival and competitiveness. Marine sponges are rich sources of natural products and have provided an infinite supply of bioactive metabolites. Bromopyrrole alkaloids are a good example of marine metabolites, have a broad range of biological activity, and represent a fascinating example of chemical diversity of secondary metabolites elaborated by marine invertebrates. The isolation and synthesis of this structural class have been investigated, resulting in a series of bromopyrrole alkaloids with potential lead hits. This review presents the detailed isolation and anticancer activity of marine bromopyrrole alkaloids, and will be of interest to the wider research community both in academic and industrial settings.

Bioactive Compounds from Marine Sponges and Algae: Effects on Cancer Cell Metabolome and Chemical Structures.

Metabolomics represent the set of small organic molecules generally called metabolites, which are located within cells, tissues or organisms. This new "omic" technology, together with other similar technologies (genomics, transcriptomics and proteomics) is becoming a widely used tool in cancer research, aiming at the understanding of global biology systems in their physiologic or altered conditions. Cancer is among the most alarming human diseases and it causes a considerable number of deaths each year. Cancer research is one of the most important fields in life sciences. In fact, several scientific advances have been made in recent years, aiming to illuminate the metabolism of cancer cells, which is different from that of healthy cells, as suggested by Otto Warburg in the 1950s. Studies on sponges and algae revealed that these organisms are the main sources of the marine bioactive compounds involved in drug discovery for cancer treatment and prevention. In this review, we analyzed these two promising groups of marine organisms to focus on new metabolomics approaches for the study of metabolic changes in cancer cell lines treated with chemical extracts from sponges and algae, and for the classification of the chemical structures of bioactive compounds that may potentially prove useful for specific biotechnological applications.

Alkaloids in Future Drug Discovery.

Alkaloids are nitrogen-containing compounds, biosynthesized by both marine and terrestrial organisms, often with strong biological properties [...].

Advance research in biomedical applications on marine sulfated polysaccharide.

Marine ecosystem associated organisms are an affluent source of bioactive compounds. Polysaccharides with unique structural and practical entities have gained special studies interest inside the current biomedical zone. Polysaccharides are the main components of marine algae, plants, animals, insects, and microorganisms. In recent times research on seaweed is more persistent for extraction of natural bioactive "Sulfated polysaccharides" (SPs). The considerable amount of SP exists in the algae in the form of fucans, fucoidans, carrageenans, ulvan, etc. Major function of SPs is to act as a defensive lattice towards the infective organism. All SPs possess the high potential and possess a broad range of therapeutic applications as antitumor, immunomodulatory, vaccine adjuvant, anti-inflammatory, anticoagulant, antiviral, antiprotozoal, antimicrobial, antilipemic, therapy of regenerative medicine, also in drug delivery and tissue engineering application. This review aims to discuss the biomedicine applications of sulfated polysaccharides from marine seaweeds.

Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library.

Staphylococcus aureus is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-N-acetylehyl-l-alanine and d-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by S. aureus. Because S. aureus is resistant to most existing antibiotics, it is necessary to develop new inhibitors. In this study, Schrodinger 11.5 Prime homology modeling was selected to prepare the protein model of MurD enzyme, and its structure was optimized. We used a virtual screening program and similarity screening to screen 47163 compounds from three marine natural product libraries to explore new inhibitors of S. aureus. ADME provides analysis of the physicochemical properties of the best performing compounds during the screening process. To determine the stability of the docking effect, a 100 ns molecular dynamics was performed to verify how tightly the compound was bound to the protein. By docking analysis and molecular dynamics analysis, both 46604 and 46608 have strong interaction with the docking pocket, have good pharmacological properties, and maintain stable conformation with the target protein, so they have a chance to become drugs for S. aureus. Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for S. aureus.

Marine organisms: Pioneer natural sources of polysaccharides/proteins for green synthesis of nanoparticles and their potential applications.

Current innovations in the marine bionanotechnology arena are supporting and stimulating developments in other fields, including nanomedicine, pharmaceuticals, sensors, environmental trends, food, and agriculture aspects. Many oceanic creatures, particularly algae, plants, bacteria, yeast, fungi, cyanobacteria, actinomyces, invertebrates, animals and sponges can survive under extreme circumstances. They can biogenerate a broad spectrum of phytochemicals/metabolites, including proteins, peptides, alkaloids, flavonoids, polyphenols, carbohydrate polymers, polysaccharides, sulfated polysaccharides, polysaccharide-protein complexes such as carrageenan, fucoidanase, fucoidan, carboxymethyl cellulose, poly-γ-glutamic acid, sugar residues with proteins, melanin, haemocyanin, etc). These products exhibit exclusive advantages that offer pioneering roles in the eco-friendly fabrication of several nanoparticles (NPs) i.e., Ag, Au, Ru, Fe2O3, Cobalt (III) Oxide (Co2O3), ZnO and Ag@AgCl within a single phase. Importantly, marine organisms can biosynthesize NPs in two modes, namely extracellular and intracellular. Biosynthesized NPs can be characterized using various methodologies among them, ultraviolet-visible spectroscopy, fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Taken together, this review focuses on the green synthesis of metallic, metallic oxides and nonmetallic NPs utilizing extracts/derivatives from marine organisms based on eco-friendly green biogenic procedures. Moreover, significant attention is given to the medicinal and industrial importance of such marine organisms mediated NPs.

An integrated molecular modeling protocol for drug screening based on conceptual density functional theory and chemoinformatics for the study of marine cyclopeptides.

An integrated molecular modeling protocol resulting from the combination of conceptual density functional theory (CDFT) chemical reactivity descriptors with several chemoinformatics tools has been used for the study of the chemical reactivity and bioactivity properties of a group of marine cyclic peptides. CP-CDFT is a branch of computational chemistry and molecular modeling dedicated to the study of peptides. The protocol allowed the estimation of the CDFT-based reactivity indices together with the associated physicochemical parameters that can help to identify the ability of the studied peptides to behave as potential useful drugs. This was complemented with an analysis of the bioactivity and pharmacokinetics parameters related to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. Some examples related to the ability of the CDFT-based chemical reactivity descriptors for the prediction of the pKas of the peptides as well as their potential as AGE inhibitors are also presented.

Jellyfish Collagen: A Biocompatible Collagen Source for 3D Scaffold Fabrication and Enhanced Chondrogenicity.

Osteoarthritis (OA) is a multifactorial disease leading to degeneration of articular cartilage, causing morbidity in approximately 8.5 million of the UK population. As the dense extracellular matrix of articular cartilage is primarily composed of collagen, cartilage repair strategies have exploited the biocompatibility and mechanical strength of bovine and porcine collagen to produce robust scaffolds for procedures such as matrix-induced chondrocyte implantation (MACI). However, mammalian sourced collagens pose safety risks such as bovine spongiform encephalopathy, transmissible spongiform encephalopathy and possible transmission of viral vectors. This study characterised a non-mammalian jellyfish (Rhizostoma pulmo) collagen as an alternative, safer source in scaffold production for clinical use. Jellyfish collagen demonstrated comparable scaffold structural properties and stability when compared to mammalian collagen. Jellyfish collagen also displayed comparable immunogenic responses (platelet and leukocyte activation/cell death) and cytokine release profile in comparison to mammalian collagen in vitro. Further histological analysis of jellyfish collagen revealed bovine chondroprogenitor cell invasion and proliferation in the scaffold structures, where the scaffold supported enhanced chondrogenesis in the presence of TGFß1. This study highlights the potential of jellyfish collagen as a safe and biocompatible biomaterial for both OA repair and further regenerative medicine applications.

Chitosan/Hyaluronic acid/Alginate and an assorted polymers loaded with honey, plant, and marine compounds for progressive wound healing-Know-how.

Biomaterials are being extensively used in regenerative medicine including tissue engineering applications, as these enhance tissue development, repair, and help in the process of angiogenesis. Wound healing is a crucial biological process of regeneration of ruptured tissue after getting injury to the skin and other soft tissue in humans and animals. Besides, the accumulation of microbial biofilms around the wound surface can increase the risk and physically obstruct the wound healing activity, and may even lead to amputation. Hence, in both acute and chronic wounds, prominent biomaterials are required for wound healing along with antimicrobial agents. This review comprehensively addresses the antimicrobial and wound healing effects of chitosan, chitin, cellulose acetate, hyaluronic acid, pullulan, bacterial cellulose, fibrin, alginate, etc. based wound dressing biomaterials fabricated with natural resources such as honey, plant bioactive compounds, and marine-based polymers. Due to their excellent biocompatibility and biodegradability, bioactive compounds derived from honey, plants, and marine resources are commonly used in biomedical and tissue engineering applications. Different types of polymer-based biomaterials including hydrogel, film, scaffold, nanofiber, and sponge dressings fabricated with bioactive agents including honey, curcumin, tannin, quercetin, andrographolide, gelatin, carrageenan, etc., can exhibit significant wound healing process in, diabetic wounds, diabetic ulcers, and burns, and help in cartilage repair along with good biocompatibility and antimicrobial effects. Among the reviewed biomaterials, carbohydrate polymers such as chitosan-based biomaterials are prominent and widely used for wound healing applications followed by hyaluronic acid and alginate-based biomaterials loaded with honey, plant, and marine compounds. This review first provides an overview of the vast natural resources used to formulate different biomaterials for the treatment of antimicrobial, acute, and chronic wound healing processes.

Naturally-derived targeted therapy for wound healing: Beyond classical strategies.

This review summarizes the four processes of wound healing in the human body (hemostasis, inflammatory, proliferation, and remodeling) and the most current research on the most important factors affecting cutaneous wound healing and the underlying cellular and/or molecular pathways. Local factors, including temperature, oxygenation, and infection, and systemic factors, such as age, diabetes, sex hormones, genetic components, autoimmune diseases, psychological stress, smoking and obesity are also addressed. A better understanding of the role of these factors in wound repair could result in the development of therapeutics that promote wound healing and resolve affected wounds. Additionally, natural products obtained from plants and animals are critical targets for the discovery of novel biologically significant pharmacophores, such as medicines and agrochemicals. This review outlines the most recent advances in naturally derived targeted treatment for wound healing. These are plant-derived natural products, insect-derived natural products, marine-derived natural products, nanomaterial-based wound-healing therapeutics (metal- and non-metal-based nanoparticles), and natural product-based nanomedicine to improve the future direction of wound healing. Natural products extracted from plants and animals have advanced significantly, particularly in the treatment of wound healing. As a result, the isolation and extraction of bioactive compounds from a variety of sources can continue to advance our understanding of wound healing. Undescribed bioactive compounds or unexplored formulations that could have a role in today's medicinal arsenal may be contained in the abundance of natural products and natural product derivatives.

Antibacterial phenylspirodrimanes from the marine-derived fungus Stachybotrys sp. SCSIO 40434.

Five new phenylspirodrimanes, stachybomycins A - E (1-5), together with four known compounds (6-9), were isolated from the marine-derived fungus Stachybotrys sp. SCSIO 40434. Their structures were elucidated by comprehensive spectroscopic analyses of NMR and HRESIMS. The absolute configuration of 1 was confirmed by single crystal X-ray diffraction analysis. Compounds 5 and 7 showed moderate antibacterial activities against Micrococcus luteus, Staphylococcus aureus and methicillin resistant Staphylococcus aureus with minimal inhibition concentration (MIC) values of 8, 16 and 16 µg mL-1, respectively.

Natural products as drugs and tools for influencing core processes of eukaryotic mRNA translation.

Eukaryotic protein synthesis is the highly conserved, complex mechanism of translating genetic information into proteins. Although this process is essential for cellular homoeostasis, dysregulations are associated with cellular malfunctions and diseases including cancer and diabetes. In the challenging and ongoing search for adequate treatment possibilities, natural products represent excellent research tools and drug leads for new interactions with the translational machinery and for influencing mRNA translation. In this review, bacterial-, marine- and plant-derived natural compounds that interact with different steps of mRNA translation, comprising ribosomal assembly, translation initiation and elongation, are highlighted. Thereby, the exact binding and interacting partners are unveiled in order to accurately understand the mode of action of each natural product. The pharmacological relevance of these compounds is furthermore assessed by evaluating the observed biological activities in the light of translational inhibition and by enlightening potential obstacles and undesired side-effects, e.g. in clinical trials. As many of the natural products presented here possess the potential to serve as drug leads for synthetic derivatives, structural motifs, which are indispensable for both mode of action and biological activities, are discussed. Evaluating the natural products emphasises the strong diversity of their points of attack. Especially the fact that selected binding partners can be set in direct relation to different diseases emphasises the indispensability of natural products in the field of drug development. Discovery of new, unique and unusual interacting partners again renders them promising tools for future research in the field of eukaryotic mRNA translation.

Macrocystis pyrifera Extract Residual as Nutrient Source for the Production of Sophorolipids Compounds by Marine Yeast Rhodotorula rubra.

Seaweed processing generates liquid fraction residual that could be used as a low-cost nutrient source for microbial production of metabolites. The Rhodotorula strain is able to produce antimicrobial compounds known as sophorolipids. Our aim was to evaluate sophorolipid production, with antibacterial activity, by marine Rhodotorula rubra using liquid fraction residual (LFR) from the brown seaweed Macrocystis pyrifera as the nutrient source. LFR having a composition of 32% w/w carbohydrate, 1% w/w lipids, 15% w/w protein and 52% w/w ash. The best culture condition for sophorolipid production was LFR 40% v/v, without yeast extract, artificial seawater 80% v/v at 15 °C by 3 growth days, with the antibacterial activity of 24.4 ± 3.1 % on Escherichia coli and 21.1 ± 3.8 % on Staphylococcus aureus. It was possible to identify mono-acetylated acidic and methyl ester acidic sophorolipid. These compounds possess potential as pathogen controllers for application in the food industry.

Cytotoxic Alkaloids Derived from Marine Sponges: A Comprehensive Review.

Marine sponges (porifera) have proved to be a prolific source of unique bioactive secondary metabolites, among which the alkaloids occupy a special place in terms of unprecedented structures and outstanding biological activities. Identification of active cytotoxic alkaloids extracted from marine animals, particularly sponges, is an important strive, due to lack of knowledge on traditional experiential and ethnopharmacology investigations. In this report, a comprehensive survey of demospongian bioactive alkaloids in the range 1987-2020 had been performed with a special emphasis on the potent cytotoxic activity. Different resources and databases had been investigated, including Scifinder (database for the chemical literature) CAS (Chemical Abstract Service) search, web of science, Marin Lit (marine natural products research) database. More than 230 representatives of different classes of alkaloids had been reviewed and classified, different genera belonging to the phylum porifera had been shown to be a prolific source of alkaloidal molecules, including Agelas sp., Suberea sp., Mycale sp., Haliclona sp., Epipolasis sp., Monanchora sp., Crambe sp., Reniera sp., and Xestospongia sp., among others. The sufficient production of alkaloids derived from sponges is a prosperous approach that requires more attention in future studies to consider the constraints regarding the supply of drugs, attained from marine organisms.

The Marine Microalga, Tisochrysis lutea, Protects against Metabolic Disorders Associated with Metabolic Syndrome and Obesity.

Long-chain polyunsaturated fatty acids n-3 series and especially docosahexaenoic acid are known to exert preventive effects on metabolic disturbances associated with obesity and decrease cardiovascular disease risk. n-3 LC-PUFAs are mainly consumed in the form of fish oil, while other sources, such as certain microalgae, may contain a high content of these fatty acids. The aim of this study was to evaluate the effects of Tisochrysis lutea (Tiso), a microalga rich in DHA, on metabolic disorders associated with obesity. Three male Wistar rat groups were submitted for eight weeks to a standard diet or high-fat and high fructose diet (HF), supplemented or not with 12% of T. lutea (HF-Tiso). The supplementation did not affect plasma alanine aminotransferase (ALAT). Bodyweight, glycemia and insulinemia decreased in HF-Tiso rats (ANOVA, p < 0.001), while total plasma cholesterol, high-density lipoprotein-cholesterol (HDL-C) increased (ANOVA, p < 0.001) without change of low-density lipoprotein-cholesterol (LDL-C) and triacylglycerol (TAG) levels. Tiso supplementation decreased fat mass and leptinemia as well as liver TAG, cholesterol and plasma tumor necrosis factor-alpha levels (ANOVA, p < 0.001) while it did not affect interleukin 6 (IL-6), IL-4 and lipopolysaccharides levels. HF-Tiso rats showed an increase of IL-10 level in abdominal adipose tissue (ANOVA, p < 0.001). In conclusion, these results indicated that DHA-rich T. lutea might be beneficial for the prevention of obesity and improvement of lipid and glucose metabolism.

Asperorydines N-P, three new cyclopiazonic acid alkaloids from the marine-derived fungus Aspergillus flavus SCSIO F025.

Three new tricyclic cyclopiazonic acid (CPA) related alkaloids asperorydines N-P (1-3), together with six known compounds (4-9) were isolated and characterized from the fungus Aspergillus flavus SCSIO F025 derived from the deep-sea sediments of South China Sea. The structures including absolute configurations of 1-3 were deduced from spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism (ECD). All compounds were evaluated for the antioxidative activities against DPPH, cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), and antimicrobial activities. Compound 9 showed significant radical scavenging activities against DPPH with an IC50 value of 62.23 µM and broad-spectrum cytotoxicities against four tumor cell lines with IC50 values ranging from 24.38 to 48.28 µM. Furthermore, compounds 4-9 exhibited weak antimicrobial activities against E scherichia coli, and compound 9 also showed antibacterial activity against Bacillus thuringiensis, Micrococcus lutea, Staphylococcus aureus, Bacillus subtilis, Methicillin resistant Staphylococcus aureus.

Tryptophan derived natural marine alkaloids and synthetic derivatives as promising antimicrobial agents.

Antimicrobial resistance has become a major threat to public health worldwide, as pathogenic microorganisms are finding ways to evade all known antimicrobials. Therefore, the demand for new and effective antimicrobial agents is also increasing. Natural products have always played an important role in drug discovery, either by themselves or as inspiration for synthetic compounds. The marine environment is a rich source of bioactive metabolites, and among them, tryptophan-derived alkaloids stand out for their abundance and by displaying a variety of biological activities, with antimicrobial properties being among the most significant. This review aims to reveal the potential of marine alkaloids derived from tryptophan as antimicrobial agents. Relevant examples of these compounds and their synthetic analogues reported in the last decades are presented and discussed in detail, with their mechanism of action and synthetic approaches whenever relevant. Several tryptophan-derived marine alkaloids have shown potent and promising antimicrobial activities, whether against bacteria, fungi, or virus. Synthetic approaches to many of the compounds have been developed and recent methodologies are proving to be efficient. Even though most of the studies regarding the antimicrobial activity are still preliminary, this class of compounds has proven to be worth of further investigation and may provide useful lead compounds for the development of antimicrobial agents. Overall, marine alkaloids derived from tryptophan are revealed as a valuable class of antimicrobials and molecular modifications in order to reduce the toxicity of these compounds and additional studies regarding their mechanism of action are interesting topics to explore in the future.

A biodegradable antibacterial alginate/carboxymethyl chitosan/Kangfuxin sponges for promoting blood coagulation and full-thickness wound healing.

Conventional wound-dressing materials with structural and functional deficiencies are not effective in promoting wound healing. The development of multifunctional wound dressings is emerging as a promising strategy to accelerate blood coagulation, inhibit bacterial infection, and trigger full-thickness wound into a regenerative process. Herein, multifunctional composite sponges were developed by incorporation of traditional Chinese medicine Kangfuxin (KFX) into alginate (AG)/carboxymethyl chitosan (CMC) via green crosslinking, electrostatic interaction, and freeze-drying methods. It is demonstrated that the AG/CMC/KFX (ACK) sponges exhibit a highly interconnected and porous structure, suitable water vapor transmittance, excellent elastic properties, antibacterial behavior, cytocompatibility, and rapid hemostasis. Further, in a rat full-thickness wounds model, the ACK sponge containing 10% KFX (ACK-10) significantly facilitates wound closure compared to the AC group and ACK sponge containing 5% and 15% KFX. Thus, the multifunctional ACK-10 composite sponge has great promise for the application of full-thickness wound healing.