Screening of Marine Bioactive Antimicrobial Compounds for Plant Pathogens

Plant diseases have been threatening food production. Controlling plant pathogens has become an important strategy to ensure food security. Although chemical control is an effective disease control strategy, its application is limited by many problems, such as environmental impact and pathogen resistance. In order to overcome these problems, it is necessary to develop more chemical reagents with new functional mechanisms. Due to their special living environment, marine organisms have produced a variety of bioactive compounds with novel structures, which have the potential to develop new fungicides. In the past two decades, screening marine bioactive compounds to inhibit plant pathogens has been a hot topic. In this review, we summarize the screening methods of marine active substances from plant pathogens, the identification of marine active substances from different sources, and the structure and antibacterial mechanism of marine active natural products. Finally, the application prospect of marine bioactive substances in plant disease control was prospected.     

Marine carotenoids and cardiovascular risk markers

Marine carotenoids are important bioactive compounds with physiological activities related to prevention of degenerative diseases found principally in plants, with potential antioxidant biological properties deriving from their chemical structure and interaction with biological membranes. They are substances with very special and remarkable properties that no other groups of substances possess and that form the basis of their many, varied functions and actions in all kinds of living organisms. The potential beneficial effects of marine carotenoids have been studied particularly in astaxanthin and fucoxanthin as they are the major marine carotenoids. Both these two carotenoids show strong antioxidant activity attributed to quenching singlet oxygen and scavenging free radicals. The potential role of these carotenoids as dietary anti-oxidants has been suggested to be one of the main mechanisms for their preventive effects against cancer and inflammatory diseases. The aim of this short review is to examine the published studies concerning the use of the two marine carotenoids, astaxanthin and fucoxanthin, in the prevention of cardiovascular diseases.     

Potential Anti-HPV and Related Cancer Agents from Marine Resources: An Overview

Recently, the studies on the prevention and treatment of human papillomavirus (HPV) which is closely related to the cervical cancer and other genital diseases are attracting more and more attention all over the world. Marine-derived polysaccharides and other bioactive compounds have been shown to possess a variety of anti-HPV and related cancer activities. This paper will review the recent progress in research on the potential anti-HPV and related cancer agents from marine resources. In particular, it will provide an update on the anti-HPV actions of heparinoid polysaccharides and bioactive compounds present in marine organisms, as well as the therapeutic vaccines relating to marine organisms. In addition, the possible mechanisms of anti-HPV actions of marine bioactive compounds and their potential for therapeutic application will also be summarized in detail.     

Statistical Research on the Bioactivity of New Marine Natural Products Discovered during the 28 Years from 1985 to 2012

Every year, hundreds of new compounds are discovered from the metabolites of marine organisms. Finding new and useful compounds is one of the crucial drivers for this field of research. Here we describe the statistics of bioactive compounds discovered from marine organisms from 1985 to 2012. This work is based on our database, which contains information on more than 15,000 chemical substances including 4196 bioactive marine natural products. We performed a comprehensive statistical analysis to understand the characteristics of the novel bioactive compounds and detail temporal trends, chemical structures, species distribution, and research progress. We hope this meta-analysis will provide useful information for research into the bioactivity of marine natural products and drug development.     

Marine Peptides and Their Anti-Infective Activities

Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present.     

Characteristics of Marine Biomaterials and Their Applications in Biomedicine

Oceans have vast potential to develop high-value bioactive substances and biomaterials. In the past decades, many biomaterials have come from marine organisms, but due to the wide variety of organisms living in the oceans, the great diversity of marine-derived materials remains explored. The marine biomaterials that have been found and studied have excellent biological activity, unique chemical structure, good biocompatibility, low toxicity, and suitable degradation, and can be used as attractive tissue material engineering and regenerative medicine applications. In this review, we give an overview of the extraction and processing methods and chemical and biological characteristics of common marine polysaccharides and proteins. This review also briefly explains their important applications in anticancer, antiviral, drug delivery, tissue engineering, and other fields.     

Potential Anti-Aging Substances Derived from Seaweeds

Aging is a major risk factor for many chronic diseases, such as cancer, cardiovascular disease, and diabetes. The exact mechanisms underlying the aging process are not fully elucidated. However, a growing body of evidence suggests that several pathways, such as sirtuin, AMP-activated protein kinase, insulin-like growth factor, autophagy, and nuclear factor erythroid 2-related factor 2 play critical roles in regulating aging. Furthermore, genetic or dietary interventions of these pathways can extend lifespan by delaying the aging process. Seaweeds are a food source rich in many nutrients, including fibers, polyunsaturated fatty acids, vitamins, minerals, and other bioactive compounds. The health benefits of seaweeds include, but are not limited to, antioxidant, anti-inflammatory, and anti-obese activities. Interestingly, a body of studies shows that some seaweed-derived extracts or isolated compounds, can modulate these aging-regulating pathways or even extend lifespans of various animal models. However, few such studies have been conducted on higher animals or even humans. In this review, we focused on potential anti-aging bioactive substances in seaweeds that have been studied in cells and animals mainly based on their anti-aging cellular and molecular mechanisms.     

Characterization of Marine Organism Extracellular Matrix-Anchored Extracellular Vesicles and Their Biological Effect on the Alleviation of Pro-Inflammatory Cytokines

Representative marine materials such as biopolymers and bioceramics contain bioactive properties and are applied in regenerative medicine and tissue engineering. The marine organism-derived extracellular matrix (ECM), which consists of structural and functional molecules, has been studied as a biomaterial. It has been used to reconstruct tissues and improve biological functions. However, research on marine-derived extracellular vesicles (EVs) among marine functional materials is limited. Recent studies on marine-derived EVs were limited to eco-system studies using bacteria-released EVs. We aimed to expand the range of representative marine organisms such as fish, crustaceans, and echinoderms; establish the extraction process; and study the bioactivity capability of marine EVs. Results confirmed that marine organism ECM-anchored EVs (mEVs) have a similar morphology and cargos to those of EVs in land animals. To investigate physiological effects, lipopolysaccharide (LPS)-infected macrophages were treated with EVs derived from sea cucumber, fish, and shrimp. A comparison of the expression levels of inflammatory cytokine genes revealed that all types of mEVs alleviated pro-inflammatory cytokines, although to different degrees. Among them, the sea cucumber-derived EVs showed the strongest suppression ability. This study showed that research on EVs derived from various types of marine animals can lead to the development of high value-added therapeutics from discarded marine wastes.     

Marine Bioactives and Potential Application in Sports

An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.     

Marine Alkaloids: Compounds with In Vivo Activity and Chemical Synthesis

Marine alkaloids comprise a class of compounds with several nitrogenated structures that can be explored as potential natural bioactive compounds. The scientific interest in these compounds has been increasing in the last decades, and many studies have been published elucidating their chemical structure and biological effects in vitro. Following this trend, the number of in vivo studies reporting the health-related properties of marine alkaloids has been increasing and providing more information about the effects in complex organisms. Experiments with animals, especially mice and zebrafish, are revealing the potential health benefits against cancer development, cardiovascular diseases, seizures, Alzheimer’s disease, mental health disorders, inflammatory diseases, osteoporosis, cystic fibrosis, oxidative stress, human parasites, and microbial infections in vivo. Although major efforts are still necessary to increase the knowledge, especially about the translation value of the information obtained from in vivo experiments to clinical trials, marine alkaloids are promising candidates for further experiments in drug development.     

Marine Carotenoids against Oxidative Stress: Effects on Human Health

Carotenoids are lipid-soluble pigments that are produced in some plants, algae, fungi, and bacterial species, which accounts for their orange and yellow hues. Carotenoids are powerful antioxidants thanks to their ability to quench singlet oxygen, to be oxidized, to be isomerized, and to scavenge free radicals, which plays a crucial role in the etiology of several diseases. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. In this respect, various novel marine carotenoids have recently been isolated from marine organisms and displayed several utilizations as nutraceuticals and pharmaceuticals. Marine carotenoids (astaxanthin, fucoxanthin, β-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. This review aims to describe the role of marine carotenoids against oxidative stress and their potential applications in preventing and treating inflammatory diseases.     

Biomaterials and Bioactive Natural Products from Marine Invertebrates: From Basic Research to Innovative Applications

Aquatic invertebrates are a major source of biomaterials and bioactive natural products that can find applications as pharmaceutics, nutraceutics, cosmetics, antibiotics, antifouling products and biomaterials. Symbiotic microorganisms are often the real producers of many secondary metabolites initially isolated from marine invertebrates; however, a certain number of them are actually synthesized by the macro-organisms. In this review, we analysed the literature of the years 2010–2019 on natural products (bioactive molecules and biomaterials) from the main phyla of marine invertebrates explored so far, including sponges, cnidarians, molluscs, echinoderms and ascidians, and present relevant examples of natural products of interest to public and private stakeholders. We also describe omics tools that have been more relevant in identifying and understanding mechanisms and processes underlying the biosynthesis of secondary metabolites in marine invertebrates. Since there is increasing attention on finding new solutions for a sustainable large-scale supply of bioactive compounds, we propose that a possible improvement in the biodiscovery pipeline might also come from the study and utilization of aquatic invertebrate stem cells.     

Anti-Alzheimer’s Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aβ) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD.     

Bioactive peptides and depsipeptides with anticancer potential: sources from marine animals

Biologically active compounds with different modes of action, such as, antiproliferative, antioxidant, antimicrotubule, have been isolated from marine sources, specifically algae and cyanobacteria. Recently research has been focused on peptides from marine animal sources, since they have been found as secondary metabolites from sponges, ascidians, tunicates, and mollusks. The structural characteristics of these peptides include various unusual amino acid residues which may be responsible for their bioactivity. Moreover, protein hydrolysates formed by the enzymatic digestion of aquatic and marine by-products are an important source of bioactive peptides. Purified peptides from these sources have been shown to have antioxidant activity and cytotoxic effect on several human cancer cell lines such as HeLa, AGS, and DLD-1. These characteristics imply that the use of peptides from marine sources has potential for the prevention and treatment of cancer, and that they might also be useful as molecular models in anticancer drug research. This review focuses on the latest studies and critical research in this field, and evidences the immense potential of marine animals as bioactive peptide sources.     

Signal Transducers and Activators of Transcription (STAT) Regulatory Networks in Marine Organisms: From Physiological Observations towards Marine Drug Discovery

Part of our ocean’s richness comes from its extensive history of supporting life, resulting in a highly diverse ecological system. To date, over 250,000 species of marine organisms have been identified, but it is speculated that the actual number of marine species exceeds one million, including several hundreds of millions of species of marine microorganisms. Past studies suggest that approximately 70% of all deep-sea microorganisms, gorgonians, and sea sponges produce secondary metabolites with anti-cancer activities. Recently, novel FDA-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. Despite the fact that many marine natural products have been shown to possess a good inhibition potential against most of the cancer-related cell signaling pathways, only a few marine natural products have been shown to target JAK/STAT signaling. In the present paper, we describe the JAK/STAT signaling pathways found in marine organisms, before elaborating on the recent advances in the field of STAT inhibition by marine natural products and the potential application in anti-cancer drug discovery.     

Bioactive Properties of Peptides and Polysaccharides Derived from Peanut Worms: A Review

Peanut worms (Sipunculids) are unsegmented marine worms that usually inhabit shallow waters. Peanut worms are good source of bioactive compounds including peptides and polysaccharides. Many recent studies have investigated the bioactive properties of peptides and polysaccharides derived from peanut worms in order to enhance their applications in food and pharmaceutical industries. The peptides and polysaccharides isolated from peanut worms have been reported to possess anti-hypertensive, anti-oxidant, immunomodulatory, anti-inflammatory, anti-cancer, anti-hypoxia and wound healing activities through the modulation of various molecular mechanisms. Most researchers used in vitro, cell culture and animal models for the determination of bioactivities of peanut worm derived compounds. However, studies in humans have not been performed considerably. Therefore, it is important to conduct more human studies for better utilization of marine bioactive compounds (peptides and polysaccharides) derived from peanut worms. This review mainly focuses on the bioactive properties of peptides and polysaccharides of peanut worms and their molecular mechanisms.     

Immense essence of excellence: marine microbial bioactive compounds

Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery.     

Antitumor peptides from marine organisms

The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.     

Bioactive Alkaloids from the Sea: A Review

In our ongoing search for bioactive substances from marine organisms, novel alkaloids have been isolated. Pinnatoxins and pinnamine, potent shellfish poisons, were purified from the Okinawan bivalve Pinna muricata. Pinnatoxins activate Ca²⁺ channels. Halichlorine was isolated from the marine sponge Halichondria okadai. This compound inhibits the induction of VCAM-1. Drugs that block VCAM-1 may be useful for treating coronary artery diseases, angina, and noncardiovascular inflammatory diseases. Pinnaic acids, which are cPLA₂ inhibitors, were also obtained from P. muricata. Interestingly, the structures of pinnaic acids are closely related to that of halichlorine. Norzoanthamine hydrochloride, isolated from the colonial zoanthid Zoanthus sp., suppresses decreases in bone weight and strength in ovariectomized mice, and could be a good candidate for an osteoporotic drug. Ircinamine, purified from the marine sponge Ircinia sp., has a reactive thioester. Aburatubolactams, inhibitors of superoxide anion generation, were isolated from Streptomyces sp. This article covers the bioactive marine alkaloids that have been recently isolated by this research group.     

Brominated compounds from marine sponges of the genus Aplysina and a compilation of their 13C NMR spectral data

Aplysina is the best representative genus of the family Aplysinidae. Halogenated substances are its main class of metabolites. These substances contribute greatly to the chemotaxonomy and characterization of the sponges belonging to this genus. Due to their pharmacological activities, these alkaloids are of special interest. The chemistry of halogenated substances and of the alkaloids has long been extensively studied in terrestrial organisms, while the number of marine organisms studied has just started to increase in the last decades. This review describes 101 halogenated substances from 14 species of Aplysina from different parts of the world. These substances can be divided into the following classes: bromotyramines (A), cavernicolins (B), hydroverongiaquinols (C), bromotyrosineketals (D), bromotyrosine lactone derivatives (E), oxazolidones (F), spiroisoxazolines (G), verongiabenzenoids (H), verongiaquinols (I), and dibromocyclohexadienes (J). A compilation of their (13)C NMR data is also part of the review. For this purpose 138 references were consulted.