Exploring the Potential of Using Marine-Derived Ingredients: From the Extraction to Cutting-Edge Cosmetics.

The growing understanding and knowledge of the potential of marine species, as well as the application of "blue biotechnology" have been motivating new innovative solutions in cosmetics. It is widely noted that that marine species are important sources of compounds with several biological activities that are yet to be discovered. This review explores various biological properties of marine-derived molecules and briefly outlines the main extraction methods. Alongside these, it is well known the legislative and normative framework of cosmetics is increasingly being developed. In this research segment, there is a growing concern with sustainability. In this sense, "blue biotechnology", together with the use of invasive species or marine waste products to obtain new active ingredients, haven been emerging as innovative and sustainable solutions for the future's cosmetics industry. This review also examines the regulatory framework and focus on the recent advancements in "blue biotechnology" and its relevance to the sustainable development of innovative cosmetics.

The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones.

The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.

Ameliorative Effect of Posidonia oceanica on High Glucose-Related Stress in Human Hepatoma HepG2 Cells.

Metabolic disorders characterized by elevated blood glucose levels are a recognized risk factor for hepatocellular carcinoma (HCC). Lipid dysregulation is critically involved in the HCC progression, regulating energy storage, metabolism, and cell signaling. There is a clear link between de novo lipogenesis in the liver and activation of the NF-κB pathway, which is involved in cancer metastasis via regulation of metalloproteinases MMP-2/9. As conventional therapies for HCC reach their limits, new effective and safe drugs need to be found for the prevention and/or adjuvant therapy of HCC. The marine plant Posidonia oceanica (L.) Delile is endemic to the Mediterranean and has traditionally been used to treat diabetes and other health disorders. The phenol-rich leaf extract of Posidonia oceanica (POE) is known to have cell-safe bioactivities. Here, high glucose (HG) conditions were used to study lipid accumulation and fatty acid synthase (FASN) expression in human HepG2 hepatoma cells using Oil Red O and Western blot assays. Under HG conditions, the activation status of MAPKs/NF-κB axis and MMP-2/9 activity were determined by Western blot and gelatin zymography assays. The potential ameliorative role of POE against HG-related stress in HepG2 cells was then investigated. POE reduced lipid accumulation and FASN expression with an impact on de novo lipogenesis. Moreover, POE inhibited the MAPKs/NF-κB axis and, consequently, MMP-2/9 activity. Overall, these results suggest that P. oceanica may be a potential weapon in the HCC additional treatment.

Marine Natural Products as Innovative Cosmetic Ingredients.

Over the course of the last 20 years, numerous studies have identified the benefits of an array of marine natural ingredients for cosmetic purposes, as they present unique characteristics not found in terrestrial organisms. Consequently, several marine-based ingredients and bioactive compounds are under development, used or considered for skin care and cosmetics. Despite the multitude of cosmetics based on marine sources, only a small proportion of their full potential has been exploited. Many cosmetic industries have turned their attention to the sea to obtain innovative marine-derived compounds for cosmetics, but further research is needed to determine and elucidate the benefits. This review gathers information on the main biological targets for cosmetic ingredients, different classes of marine natural products of interest for cosmetic applications, and the organisms from which such products can be sourced. Although organisms from different phyla present different and varied bioactivities, the algae phylum seems to be the most promising for cosmetic applications, presenting compounds of many classes. In fact, some of these compounds present higher bioactivities than their commercialized counterparts, demonstrating the potential presented by marine-derived compounds for cosmetic applications (i.e., Mycosporine-like amino acids and terpenoids' antioxidant activity). This review also summarizes the major challenges and opportunities faced by marine-derived cosmetic ingredients to successfully reach the market. As a future perspective, we consider that fruitful cooperation among academics and cosmetic industries could lead to a more sustainable market through responsible sourcing of ingredients, implementing ecological manufacturing processes, and experimenting with inventive recycling and reuse programs.

Malachite green and leucomalachite green in fish: a global systematic review and meta-analysis.

Malachite green (MG), an antibiotic with antifungal activity, is illegally used in aquaculture. Given that this chemical is teratogenic and mutagenic, abstinence from intake seems to be a need for public safety. The goal of this systematic review and meta-analysis was to determine the global contamination of fishes by MG and its reduced metabolite, leucomalachite green (LMG), in a number of marine and farmed fish species. For literature published prior to January 2022, several databases (Web of Science, PubMed, and Scopus) were investigated. In total, 20 publications (10 countries, 724 samples) achieved the criteria for inclusion. The overall average MG and LMG concentrations were 0.48 (95% CI: 0.47, 0.49 µg kg-1) and 0.59 (95% CI: 0.39, 0.79 µg/kg-1), respectively. Eel (M. albus) 15.50 (95% CI: (14.39, 45.39 µg kg-1) and eel (A. anguilla) 4.46 (95% CI: 1.23, 7.69 µg kg-1) had the greatest contamination of MG and LMG, according to the effect size, respectively. Warm-water fish had a concentration of 2.591 (95% CI: 2.25, 2.93 µg kg-1) while cold-water fish had a concentration of 1.55 (95% CI: 0.25, 2.84 µg kg-1). Fish containing medium-fat level of 1.86 (95% CI: 1.27, 2.44 µg kg-1) and high-fat content of 1.10 (95% CI: 0.93, 1.26 µg kg-1) had accumulate MG and LMG in their tissues, respectively. As a result, total MG observed in countries including China, Iran, and the Netherlands was higher than authorized (2 µg kg-1). The toxicity of MG and LMG demands more monitoring, especially in countries where these chemicals' residues are significant.

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19.

Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

Natural Marine Products: Anti-Colorectal Cancer In Vitro and In Vivo.

Colorectal cancer, a malignant tumor with high mortality, has a poor prognosis due to drug resistance and toxicity in clinical surgery and chemotherapy. Thus, finding safer and more efficient drugs for clinical trials is vital and urgent. Natural marine compounds, with rich resources and original chemical structures, are applied widely in anticancer treatments. We provide a systematic overview of recently reported marine compounds such as alkaloids, peptides, terpenoids, polysaccharides, and carotenoids from in vitro, in vivo, and clinical studies. The in vitro studies summarized the marine origins and pharmacological mechanisms, including anti-proliferation, anti-angiogenesis, anti-migration, anti-invasion, the acceleration of cycle arrest, and the promotion of tumor apoptosis, of various compounds. The in vivo studies outlined the antitumor effects of marine compounds on colorectal cancer model mice and evaluated their efficacy in terms of tumor inhibition, hepatotoxicity, and nephrotoxicity. The clinical studies summarized the major chemical classifications and targets of action of the clinical drugs that have entered clinical approval and completed approval for marine anticancer. In summary, we present the current situation regarding the application of natural anti-colorectal cancer marine compounds and prospects for their clinical application.

Antitumor Potential of Immunomodulatory Natural Products.

Cancer is one of the leading causes of death globally. Anticancer drugs aim to block tumor growth by killing cancerous cells in order to prevent tumor progression and metastasis. Efficient anticancer drugs should also minimize general toxicity towards organs and healthy cells. Tumor growth can also be successfully restrained by targeting and modulating immune response. Cancer immunotherapy is assuming a growing relevance in the fight against cancer and has recently aroused much interest for its wider safety and the capability to complement conventional chemotherapeutic approaches. Natural products are a traditional source of molecules with relevant potential in the pharmacological field. The huge structural diversity of metabolites with low molecular weight (small molecules) from terrestrial and marine organisms has provided lead compounds for the discovery of many modern anticancer drugs. Many natural products combine chemo-protective and immunomodulant activity, thus offering the potential to be used alone or in association with conventional cancer therapy. In this review, we report the natural products known to possess antitumor properties by interaction with immune system, as well as discuss the possible immunomodulatory mechanisms of these molecules.

Naming of new natural products: Standard, pitfalls and tips-and-tricks.

Naming a newly discovered natural product (NP) is a pleasant but difficult exercise. In most cases, the NP name will be given with reference to the species of origin, be it a plant, a marine organism, a mammalian or microbial species. For a long time, the use of biologically-based trivial names has been recommended to identify the parental linkage between the product and the originating genus or species. But the recommendation is not always followed and a multiplicity of trivial names have been attributed to NP, based on locations (country, region, city), foods, music, animals, forenames, etc. Tips-and-tricks associated with the naming of NP are underlined here. Usually, NP are differentiated across a homogeneous chemical series with a letter (from the Latin or Greek alphabet), followed or not with a number. In other cases, the change of a single letter distinguishes a series of NP. Common pitfalls associated with the naming of NP are enumerated, including the complexity of names, use of synonyms, duplicated names, confusing names and inappropriate terminology. The difficulties regularly encountered with the naming of NP are discussed. Four essential recommendations are recalled: (i) a thorough analysis of the existing products to avoid duplicated names and confusion, (ii) the use of a biologically-based trivial name to retrace the origin of the product, (iii) the strict adherence to the codes of chemical nomenclature, and (iv) the preference for simple names to facilitate transmission. Naming a new NP is a rewarding task, which shall be performed with all due skill, care and diligence.

Developing natural marine products for treating liver diseases.

In recent years, marine-derived bioactive compounds have gained increasing attention because of their higher biodiversity vs land-derived compounds. A number of marine-derived compounds are proven to improve lipid metabolism, modulate the gut microbiota, and possess anti-inflammatory, antioxidant, antibacterial, antiviral, and antitumor activities. With the increasing understanding of the molecular landscape underlying the pathogenesis of chronic liver diseases, interest has spiked in developing new therapeutic drugs and medicine food homology from marine sources for the prevention and treatment of liver diseases.

Marine Products As a Promising Resource of Bioactive Peptides: Update of Extraction Strategies and Their Physiological Regulatory Effects.

Marine products are a rich source of nutritional components and play important roles in promoting human health. Fish, mollusks, shellfish, as well as seaweeds are the major components of marine products with high-quality proteins. During the last several decades, bioactive peptides from marine products have gained much attention due to their diverse biological properties including antioxidant, antihypertensive, antimicrobial, antidiabetic, immunoregulation, and antifatigue. The structural characteristics of marine bioactive peptides largely determine the differences in signaling pathways that can be involved, which is also an internal mechanism to exert various physiological regulatory activities. In addition, the marine bioactive peptides may be used as ingredients in food or nutritional supplements with the function of treating or alleviating chronic diseases. This review presents an update of marine bioactive peptides with the highlights on the novel producing technologies, the physiological effects, as well as their regulation mechanisms. Challenges and problems are also discussed in this review to provide some potential directions for future research.

Bioactive Marine Xanthones: A Review.

The marine environment is an important source of specialized metabolites with valuable biological activities. Xanthones are a relevant chemical class of specialized metabolites found in this environment due to their structural variety and their biological activities. In this work, a comprehensive literature review of marine xanthones reported up to now was performed. A large number of bioactive xanthone derivatives (169) were identified, and their structures, biological activities, and natural sources were described. To characterize the chemical space occupied by marine-derived xanthones, molecular descriptors were calculated. For the analysis of the molecular descriptors, the xanthone derivatives were grouped into five structural categories (simple, prenylated, O-heterocyclic, complex, and hydroxanthones) and six biological activities (antitumor, antibacterial, antidiabetic, antifungal, antiviral, and miscellaneous). Moreover, the natural product-likeness and the drug-likeness of marine xanthones were also assessed. Marine xanthone derivatives are rewarding bioactive compounds and constitute a promising starting point for the design of other novel bioactive molecules.

Natural Products as Potential Antiviral Drugs: The Specific Case of Marine Biotoxins.

To fight against various viral infections researchers turned to new chemical structures resulting from natural medicinal plants and more recently from "marine origin" as sources of active molecules against viral infections. The present manuscript describes complex marine origin drugs, their chemical complex structure, their therapeutic use, and their antiviral properties. Emphasis is placed more particularly on the properties of ionic channels (Na+, K+, Ca2+) blockers compounds from marine origin, named Dinotoxins, derived from "dinoflagellates microalgae". These compounds are of particular pharmaceutical interest since ionic channels blockers could be used to fight against a wide diversity of viruses, including SARS-CoV2 virus.

Overview of Natural Antiplasmodials from the Last Decade to Inspire Medicinal Chemistry.

BACKGROUND: Despite major advances in the fight against this parasitic disease, malaria remained a major cause of concern in 2021. This infection, mainly due to Plasmodium falciparum, causes more than 200 million cases every year and hundreds of thousands deaths in the developing regions, mostly in Africa. The last statistics show an increase in the cases for the third consecutive year; from 211 million in 2015, it has reached 229 million in 2019. This trend could be partially explained by the appearance of resistance to all the used antimalarials, including artemisinin. Thus, the design of new anti- Plasmodium compounds is an urgent need. For thousands of years, nature has offered humans medicines to cure their diseases or the inspiration for the development of new active principles. It then seems logical to explore the natural sources to find new molecules to treat this parasitosis. METHODS: Therefore, this review reports and analyzes the extracts (plants, bacteria, sponges, fungi) and the corresponding isolated compounds, showing antiplasmodial properties between 2013 and 2019. RESULTS AND CONCLUSION: Nature remains a major source of active compounds. Indeed, 648 molecules from various origins, mostly plants, have been reported for their inhibitory effect on Plasmodium falciparum. Among them, 188 scaffolds were defined as highly active with IC50 ≤ 5 µM, and have been reported here in detail. Moreover, the most active compounds showed a large variety of structures, such as flavonoids, triterpenes, and alkaloids. Therefore, these compounds could be an interesting source of inspiration for medicinal chemists; several of these molecules could become the next leads for malaria treatment.

A reusable AuNPS with increased stability applied for fast screening of trace heavy metals in edible and medicinal marine products.

Heavy metal pollution in marine environment poses a severe threat to the safety of marine products and is thus causing increasingly concerns in terms of their toxicity and potential health risks pose to human. Due to the complex matrix of marine products, a fast screening method for heavy metals at trace level with low price, reusability, high accuracy and long lifetime is of urgency and necessity for consumers and processing factories. This work described a simplified screening system through the preparation, characterization and particular application of Au nano particle sensor (AuNPS) in the complex marine matrix, the main aim is to significantly increase the stability, sensitivity and lifetime of detection system dedicated to Cu and Hg trace analysis in marine products. It is worth mentioning that, the proposed screening system was characterized through electrochemical experiments and theoretical calculations, which could be a new evidence for selecting the detection system in commercially complex samples. Importantly, the discipline of deposition and oxidative stripping process on AuNPS was explained based on the mechanism of Metal Ion Deficient Layer (MIDL), and illustrated with SEM changes during stripping process, as well as the dissolving-out rate of metals on AuNPS material. Moreover, to further improve the reusability and stability of AuNPS sensor, the complex marine matrix was purified by pre-plating interferences on indium tin oxide glass electrode. The screening system exhibited a liner response in the range of 0.02-0.10 µg mL-1 for Hg, 0.01-0.10 µg mL-1 and 0.001-0.01 µg mL-1 for Cu with the detection limits of 0.138 mg kg-1 and 1.51 mg kg-1 in marine matrix, respectively. The sensitivity and lifetime was at least two times better as compared to similar works even after 20-times use. Finally, this proposed analysis system combined with purification procedure was successfully applied for the edible and medicinal marine products analysis, meanwhile, the accuracy and stability were confirmed with standard analytical methods.

Advances in the Study of Marine Products with Lipid-Lowering Properties.

With twice the number of cancer's deaths, cardiovascular diseases have become the leading cause of death worldwide. Atherosclerosis, in particular, is a progressive, chronic inflammatory cardiovascular disease caused by persistent damage to blood vessels due to elevated cholesterol levels and hyperlipidemia. This condition is characterized by an increase in serum cholesterol, triglycerides, and low-density lipoprotein, and a decrease in high-density lipoprotein. Although existing therapies with hypolipidemic effects can improve the living standards of patients with cardiovascular diseases, the drugs currently used in clinical practice have certain side effects, which insists on the need for the development of new types of drugs with lipid-lowering effects. Some marine-derived substances have proven hypolipidemic activities with fewer side effects and stand as a good alternative for drug development. Recently, there have been thousands of studies on substances with lipid-lowering properties of marine origin, and some are already implemented in clinical practice. Here, we summarize the active components of marine-derived products having a hypolipidemic effect. These active constituents according to their source are divided into algal, animal, plant and microbial and contribute to the development and utilization of marine medicinal products with hypolipidemic effects.

Hypoxia-Inducible Factor Inhibitors Derived from Marine Products Suppress a Murine Model of Neovascular Retinopathy.

Neovascular retinal degenerative diseases are the leading causes of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) therapy is commonly used to treat these diseases currently. However, recent reports indicate that long term suppression of VEGF in the eye is associated with chorioretinal atrophy. Therefore, a physiological amount of VEGF is required for retinal homeostasis. Hypoxia-inducible factor (HIF) is a transcriptional factor upstream of VEGF. We previously reported that HIF regulated pathological angiogenesis in the retina of murine models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. Most of the known HIF inhibitors are anti-cancer agents which may have systemic adverse effects in for clinical use; thus, there is a need for safer and less invasive HIF inhibitors. In this study, we screened marine products, especially fish ingredients, and found that six species of fish had HIF inhibitory effects. Among them, administration of Decapterus tabl ingredients significantly suppressed retinal neovascular tufts by inhibiting HIF expression in a murine oxygen-induced retinopathy model. These results indicate that particular fish ingredients can act as anti-angiogenic agents in retinal neovascularization diseases.

Anticancer activity of Turkish marine extracts: a purple sponge extract induces apoptosis with multitarget kinase inhibition activity.

Marine natural products have drawn a great deal of attention as a vital source of new drugs for the last five decades. However, marine organisms in the seas surrounding Turkey (the Black Sea, the Aegean Sea and the Mediterranean Sea) haven't been yet extensively explored. In the present study, three marine organisms (Dysidea avara, Microcosmus sabatieri and Echinaster sepositus) were sampled from the Dardanelles (Turkish Straits System, Western Turkey) by scientific divers, transferred to the laboratory and then were extracted with 70% ethanol. The extracts were tested for their cytotoxic effect against K562, KMS-12PE, A549, and A375 cancer cell lines. The sponge extract elicited the most promising cytotoxic activity, thus it was further evaluated against H929, MCF-7, HeLa, and HCT116 cancer cells. Most of the designated cells showed a considerable sensitivity for the sponge extract particularly H929, K562, KMS-12PE and HeLa cells with IC50 less than 10 µg/mL. On the contrary, the other two extracts exhibited no cytotoxic activity on all cells at 100 µg/mL concentration. The sponge extract was tested for its capacity to induce apoptosis in cancer cells and to inhibit a panel of tyrosine kinases showing remarkable results. The outcome of this study represents a platform for discovery of new chemotherapeutic agents of marine natural origin.

Distribution of 239,240Pu in marine products from the seas around the Korean Peninsula after the Fukushima nuclear power plant accident.

In March 2011, an earthquake caused the shutdown of the active reactors at the Fukushima Daiichi Nuclear Power Plant (NPP), with the succeeding tsunami resulting in the release of radioactively contaminated water into the adjacent Japanese coastal waters. Marine biota selected from various trophic levels were collected in Korean coastal waters throughout 2014 and 2015 and their plutonium levels were measured to evaluate the radioactive contamination levels in the marine organisms that constitute the primary seafood diet in the Republic of Korea (ROK). The results showed that the activity concentrations of 239,240Pu in plankton, macroalgae, mollusks, crustaceans, and cephalopods ranged from 13 to 58, 0.64 to 0.80, 0.94 to 5.40, 0.06 to 0.50, and 0.26 mBq kg-1 of wet weight (w.w.), respectively. The activity concentrations of 239,240Pu measured in the muscles of fish varied from 0.09 to 0.30 mBq kg-1 (w.w.), relatively low values compared to those in other groups regardless of fish species, size, and sampling area. The concentration characteristics of 239,240Pu in the various organs in the respective marine products revealed that the internal organs showed higher concentrations than the muscle or skin (or exoskeleton). The highest concentration of 239,240Pu was measured in the viscera of an abalone, which had an activity concentration of 6.31 mBq kg-1 (w.w.). The concentration factors (CFs) in the >300-µm fraction of plankton and in anchovy, shrimp, and mackerel ranged 67-84% of the International Atomic Energy Agency (IAEA)-recommended values, although the CF in macroalgae was much lower at approximately 5% of IAEA values, suggesting a wide range of 239,240Pu CF in macroalgae. The mean transfer factor (TF) between macroalgae (0.6-0.8 mBq kg-1) and abalone (5.4 mBq kg-1) was estimated to be 7.5, implying that effective Pu transfer occurred between the two species. These figures equate to annual effective doses of 239,240Pu to Koreans through consumption of macroalgae, shellfish, and fish of 1.8 × 10-6, 1.4 × 10-6, and 7.1 × 10-7 mSv yr-1, respectively, and a total dose of 3.9 × 10-6 mSv yr-1, values that are negligible compared to the annual effective dose limit of 1 mSv yr-1.