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19

Marine Pharmacognosy

Mamta Kumari, Piyushkumar Sadhu, Niyati Shah, Chitrali Talele
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Vadodara, India

19.1 Introduction

Marine pharmacognosy is the component of pharmacognosy that studies natural compounds originating from marine creatures for possible pharmacological and therapeutic appli­cations. It is a subbranch of terrestrial pharmacognosy. It involves the exploration, isolation, characterization, and uti­lization of bioactive compounds from marine sources, such as algae, sponges, corals, molluscs, and various microorgan­isms found in marine environments [1, 2]. These organisms have evolved a number of techniques for flourishing in harsh settings, such as severe temperatures, salinity, pressure, vari­able degrees of oxygenation, radiation exposure, mutagenesis effects, and defenses against infection, fouling, and prolifera­tion by other organisms. Marine organisms have evolved unique chemical defenses and adaptations to survive in chal­lenging underwater ecosystems. These chemical compounds often possess intriguing biological activities and can be valu­able resources for drug discovery and development, as they may exhibit potential applications in treating various human ailments, including cancer, inflammation, viral and bacterial diseases, neurological disorders, and other therapeutic prop­erties [3]. Additionally, marine pharmacognosy serves an important function in biodiversity conservation, as the dis­covery and effective utilization of marine resources will result in a deeper comprehension of marine ecosystems and the protection of threatened species.

19.1.1 Exploring Marine Organisms for Bioactive Compounds

The oceanic environment is residence to an extensive and abundance of organisms, many of which produce unique and valuable bioactive compounds. Pharmaceuticals, nutra-
ceuticals, cosmetics, and manufacturing products are just a few of the many uses for these molecules that may be devel­oped [4]. Exploring marine organisms for bioactive com­pounds is a complex and challenging task, but it is also a rewarding one. There are various steps involved in explor­ing marine organisms for bioactive compounds, such as first starting from the sampling and collection, which involves the collection of samples of marine organisms from various environments, often using deep-sea submersi­bles, remotely operated vehicles (ROVs), or traditional col­lection methods. Then, extraction and isolation will be done from the collected sample. The isolated compounds are sub­jected to a battery of biological assays and screening tests to assess their potential activities and therapeutic applica­tions; this helps to identify promising candidates. Advanced analytical methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectroscopy (MS), are uti­lized to the chemical composition of promising substances [5]. Compounds with significant bioactivity are further studied for their safety, efficacy, and commercial viability. They may be developed into pharmaceutical drugs, nutra­ceuticals, cosmeceuticals, or other applications. Researchers also assess the environmental impact of collecting marine organisms and consider sustainable harvesting practices to protect fragile marine ecosystems.

19.1.2 Importance of Marine Organism in Drug Discovery

Novel components with potential uses in medication deliv­ery can be found in abundance in marine creatures. The biocompatibility of marine chemicals serves as one of their most crucial features for medication administration. This means that they are well-tolerated by the body and can be
372 19 Marine Pharmacognosy
used to deliver drugs to specific tissues without causing side effects. Marine compounds are also often biodegradable, meaning that they can be broken down by the body over time [6].
Another important property of marine compounds for drug delivery is their ability to target specific cells and tissues. This is because many marine compounds are naturally attracted to certain molecules or receptors on cell surfaces. This targeting ability can be used to deliver drugs more efficiently and reduce side effects. Marine compounds are also being used to develop new drug delivery systems that can overcome some of the challenges of traditional methods. For example, marine-derived hydrogels are being developed to deliver drugs to the brain, which is difficult to do with conventional methods. Some specific examples of how marine organisms are being used in drug delivery are as follows [7]:
1. Alginate: A polysaccharide derived from brown algae,
alginate is used to make biodegradable capsules and beads that can be used to deliver drugs orally or by injection.
2. Chitosan: A polysaccharide derived from shrimp
shells, chitosan is used to make mucoadhesive films and nanoparticles that can be used to deliver drugs to the nasal cavity, lungs, and eyes.
3. Fucoidan: A polymer obtained from brown algae,
fucoidan is being developed to deliver drugs to the brain and to target cancer cells.
4. Hyaluronic acid: A polysaccharide found in many
marine organisms, hyaluronic acid is used to make hydrogels and other drug delivery systems that can be used to deliver drugs to the skin, joints, and other tissues.
Researchers in marine pharmacognosy work to identify, extract, and study these bioactive compounds, aiming to develop new drugs, pharmaceuticals, or nutraceuticals that can benefit human health. This field is crucial not only for expanding the pharmaceutical industry’s drug development pipeline but also for preserving and

19.2 Marine Ecosystems and Biodiversity

Marine ecosystems encompass a vast and diverse array of environments that cover over 70% of the Earth’s surface. They range from the sunlight and shallow waters of coral reefs to the mysterious depths of the abyssal zone in the ocean’s trenches. This explores the multifaceted world of marine ecosystems and the rich tapestry of life they host.

19.2.1 Types of Marine Ecosystems

i) Coral Reefs: These vibrant and biologically diverse
ecosystems are often called the “rainforests of the sea.” They are home to an incredible variety of spe­cies, including colorful corals, fish, and invertebrates. Coral reefs are known for their delicate balance and sensitivity to environmental changes [8].
ii) Mangrove Forests: Mangroves are coastal ecosystems
that thrive in brackish water. They serve as important breeding grounds for marine life, provide protection against coastal erosion, and house a unique commu­nity of organisms adapted to the challenging condi­tions of saltwater and fluctuating tides [9].
iii) Deep-sea Habitats: The deepest part of the ocean is one
of the Earth’s least accessible and most harsh regions. It includes hydrothermal vent fields, cold seeps, and the pitch-black abyssal plain. Organisms in these zones have adapted to extreme pressure, low temperatures, and the absence of sunlight [10].
iv) Intertidal Zones: It is a zone where the sea intersects
the land, characterized by the ebb and flow of tides. It is home to a dynamic community of species that must endure constant exposure to the elements and frequent changes in water levels [11].

19.2.2 Biodiversity in Marine Environments

Marine biodiversity encompasses an astounding array of life forms, from the tiniest microorganisms to the largest whales. It includes the following [12, 13]:
i) Microorganisms: These include bacteria, viruses, and
single-celled organisms like phytoplankton. Microbes play crucial roles in marine ecosystems, serving as the foundation of the marine food web and producing a huge variety of bioactive compounds.
ii) Macroalgae: Also known as seaweeds, these large pho-
tosynthetic organisms are essential for providing habi­tat and food for marine creatures. Some macroalgae are resources of bioactive chemicals used in pharma­ceuticals and cosmetics.
iii) Invertebrates: Marine invertebrates, such as sponges,
mollusks, and echinoderms are known for their remarkable variation and the potential to generate bio­logically active compounds that have medicinal potential.
iv) Fish and Marine Mammals: Many species of fish and
underwater creatures have been explored for their potential benefits to yield bioactive compounds used in the treatment of various diseases.

19.3 Bioactive Compounds from Marine Microorganisms

373

19.2.3 Adaptations and Survival Strategies

Marine organisms have evolved remarkable adaptations to thrive in their specific environments. These adaptations include [14–16];
i) Extreme Temperature Tolerance: Some species can
endure extreme cold in polar regions or extreme heat in hydrothermal vents.
ii) High-pressure Adaptations: Deep-sea creatures are
adapted to withstand immense pressure, often exceed­ing 1000 times the atmospheric pressure at sea level.
iii) Bioluminescence and Camouflage: Many marine
organisms use bioluminescence for communication and predation avoidance, while others employ camou­flage to hide from predators or prey.
iv) Symbiotic Relationships: Mutualistic partnerships
between species, such as coral and zooxanthellae, pro­vide advantages like nutrient exchange and protection.

19.2.4 Ecosystem Services Provided by Marine Biodiversity

Marine ecosystems provide a diverse set of ecological advantages, comprising:
i) Climate Regulation: Oceans absorb carbon dioxide
) and help regulate global climate patterns.
(CO
2
ii) Fisheries and Aquaculture: Marine ecosystems sup-
port valuable fisheries and aquaculture industries, pro­viding essential food sources for human populations.
iii) Medicinal Resources: Marine organisms produce bio-
active compounds with therapeutic potential.
iv) Coastal Protection: Coastal ecosystems like mangroves
function as natural barriers against surges from thun­derstorms and erosion. The significance of these ser­vices for both the environment and human well-being cannot be overstated [14, 16–18].

19.2.5 Biodiversity Threats and Conservation

Despite their importance, marine ecosystems and biodiver­sity are facing numerous threats [10, 14]:
i) Climate Change: Rising temperatures, ocean acidifica-
tion, and sea-level rise are affecting marine habitats and species distribution.
ii) Pollution: Contaminants from land-based sources,
including plastics and chemical pollutants, and harm marine life.
iii) Overfishing: Unsustainable fishing practices deplete
fish stocks and disrupt marine food webs.
iv) Habitat Destruction: Coastal development, destructive
fishing methods, and mining activities damage critical marine habitats.
Conservation efforts focus on mitigating these threats through initiatives such as marine-protected areas, sus­tainable fisheries management, and habitat restoration. The diverse marine ecosystems, ranging from coral reefs and mangroves to deep-sea extremophiles and intertidal species, offer a wealth of unique bioactive compounds that hold significant promise for pharmaceutical applications. These compounds, characterized by their varied chemical structures and mechanisms of action, are emerging as attractive candidates for drug development. Furthermore, the immense biodiversity within marine environments is a cornerstone of the quest for novel bioactive compounds [19]. This rich diversity, encompassing a wide array of marine organisms, serves as an invaluable wellspring for the discovery of potential medicines. Scientists are contin­uously engaged in the exploration of this vast biodiversity, diligently seeking out compounds with therapeutic poten­tial to address pressing medical needs.
19.3 Bioactive Compounds from Marine Microorganisms
Bioactive chemicals generated from marine microorganisms encompass a diverse array of natural molecules generated by minute life forms inhabiting Earth’s oceans and various aquatic ecosystems. These marine microorganisms form a heterogeneous group, encompassing bacteria, archaea, fungi, algae, protozoa, and even viruses. They flourish in oceanic settings, having evolved to adverse circumstances, such as high atmospheric pressure, frigid temperatures, vari­able accessibility to light, and salt [20]. These microorgan­isms inhabit various regions of the sea, spanning from the top streams to its bottom, and can also be found in diverse marine ecosystems, such as underwater coral reefs, seagrass meadows, and mangrove swamps. They play a vital role in aquatic environments and provide a rich supply of bioactive chemicals. Bioactive chemicals derived from marine micro­organisms display a diverse range of biological actions, including antibacterial, anticytotoxic, and anti-inflamma­tory properties, antioxidant, antiviral, immunomodulatory, cardiovascular protective, neuroprotective, and more. These compounds hold significant potential for the manufacturing of novel medicines, commodities for agriculture, and indus­trial components [21]. Marine microorganisms are being studied thoroughly for potential application in biotechnology­related fields, including bioremediation, biofuel generation,
374 19 Marine Pharmacognosy
and bioplastics. These microorganisms possess unique enzymatic capabilities and biochemical pathways that can be harnessed for industrial purposes [22]. Despite their promise, the isolation and cultivation of marine microorganisms present considerable challenges, primarily due to their specific environmental requirements.

19.3.1 Microbial Diversity in the Marine Environment

i) Bacteria: Marine bacteria constitute a substantial portion
of the microbial diversity in oceans. They are highly adaptable and have evolved to inhabit a diverse variety of niches, from deepest ocean hydrothermal vents to surface waters. Examples include Cyanobacteria, Streptomyces, Pseudoalteromonas, and Vibrio which are prolific produc­ers of bioactive compounds, which produce bioactive compounds like antibiotics and actinobacteria, known for their role in antibiotic discovery [23, 24].
ii) Fungi: Marine fungi, while less explored than terres-
trial equivalents, play significant roles in marine eco­systems. They are involved in nutrient cycling and can produce bioactive secondary metabolites, including compounds with antiviral, anticancer, and immuno­suppressive properties [25, 26].
iii) Algae: Microscopic and large seaweed play crucial roles
in marine ecosystems, generating a range of bioactive substances. These include immunomodulatory poly­saccharides and antioxidants in the form of pigments. Furthermore, marine algae represent a promising res­ervoir for prospective pharmaceuticals, nutraceuticals, and applications in biotechnology [27].
iv) Viruses: Marine viruses, particularly bacteriophages
that infect marine bacteria, are abundant and influ­ence microbial communities. Some marine phages produce enzymes with biotechnological applications, while others can modulate bacterial populations, impacting marine ecosystems [24].

19.3.2 Isolation and Characterization Techniques

1. Cultivation and Fermentation: This is the traditional
method of isolating marine microorganisms. In this method, samples from the marine environment are collected and cultured in the laboratory. The resulting cultures are then screened for the synthesis of bioac­tive substances. Metagenomics: This process involves extracting DNA directly from environmental samples to identify and characterize the genetic potential of unculturable microorganisms. This allows researchers to identify novel groups of biosynthetic genes for bio­active chemical synthesis [28, 29].
2. Chemical Extraction: Once cultivated, marine micro-
organisms are processed to extract bioactive com­pounds. Various solvents and extraction methods are employed to obtain these compounds from microbial biomass.
3. Analytical Techniques: Sophisticated analytical meth-
ods, including NMR spectroscopy, mass spectrometry (MS), and X-ray crystallography, are employed to assess the structure and characteristics of isolated bio­active substances [30].

19.3.3 Pharmaceutical Applications

1. Antibiotics: Marine-derived antibiotics like
Salinosporamide A have been investigated for possible use as novel medicinal products to combat antibiotic­resistant bacteria [21].
2. Anticancer agents: Compounds from marine microor-
ganisms, such as Eribulin (derived from a marine sponge), have demonstrated effectiveness against vari­ous cancer types.
3. Antivirals: Some marine-derived compounds have
shown promise in inhibiting viral infections, including HIV and herpes viruses.
Table 19.1 Bioactive compounds from marine microorganisms.
Compound name Source Biological activity Health benefits References
Amphidinol 22 Dinoflagellate
Amphidinium Carterae
Dentigerumycin E Streptomyces sp. Antiproliferative and
Bagremycins F & G Streptomyces sp. Antiproliferative and
Abyssomicin Verrucosispora sp. Inhibitory effect against
Inhibit DNA synthesis, induction of ROS production, apoptosis
antimetastatic activity
induce apoptosis
influenza A virus
Cytotoxicity and antifungal [27]
Antitumoral [31]
Antimicrobial and antibacterial [32]
Antiviral [33]

19.4 Marine Algae and Their Medicinal Potential

Compound name Source Biological activity Health benefits References
375
Aspergillsteroid A Aspergillus sp. Disruption of cell
Equisetin Fusarium sp. Good inibitors of
membrane
HIV-integration
4. Anti-inflammatories: Marine bioactive compounds
can exhibit anti-inflammatory properties, which are valuable in treating conditions like arthritis.
5. Pain Management: Certain compounds have analgesic
properties and can be used for pain relief.
6. Neurological Disorders: The prospective use of marine
bioactive chemicals is now being studied for treating neurological disorders like Alzheimer’s disease (AD).
Some bioactive compounds from microorganisms showing different pharmacological action are listed in Table 19.1.
19.4 Marine Algae and Their Medicinal Potential
Microalgae encompass a variety of photoautotrophic organ­isms belonging to various phyla, including Cyanophyta,
Chlorophyta, Rhodophyta, Haptophyta, Streptophyta, and Heterokontophyta. These microorganisms synthesize intri-
cate organic compounds, known as primary and secondary metabolites, through the utilization of water, CO energy [36]. Microalgae demonstrate remarkable adaptabil­ity to diverse environmental stressors, allowing them to suc­ceed in many different fields of conditions, spanning from freshwater to highly saline environments. They can even flourish in damp environments, dark soils, and arid desert sands, extending their presence to lofty altitudes within the atmosphere [37].
Microalgae are recognized for their cosmeceutical poten­tial, primarily attributed to their impressive ability to respond to environmental stressors. Cosmeceuticals, which encom­pass products containing biologically active components offering therapeutic or medicinal advantages, aim to enhance skin structure, morphology, and overall appearance. Within microalgae, polysaccharides are notably prominent among these active compounds. They hold substantial promise for applications related to preventing blemishes, promoting skin repair, and mitigating inflammation, as exemplified by gen­era like Chlorella [38, 39]. Consequently, these polysaccha­rides are utilized in the formulation of thickening agents, moisturizers, and gelling agents. Furthermore, microalgae exhibit nutraceutical properties, featuring compounds, such as phycocyanin, astaxanthin, beta-carotene, fucoxanthin, lutein, lycopene, phycobiliproteins, and more.
, and solar
2
Figure 19.1 Cyanobacteria as Cyanobacterium [40].

19.4.1 Diversity of Marine Macroalgae

19.4.1.1 Cyanobacteria as Marine Microalgae
Within the realm of marine microalgae, which constitute the foundation of phytoplankton, three primary categories emerge: cyanobacteria, diatoms (Bacillariophyta), and dino­flagellates (Dinophyceae) [40] (Figure 19.1). These microal­gae boast considerable biochemical diversity, leading to the identification of numerous innovative bioactive compounds with pharmaceutical potential. Some of these substances have displayed potent antiviral and anti-HIV characteristics [41]. Recent breakthroughs have given rise to a natural anti­AIDS medication sourced from Lyngbya lagerhaimanii and
Phormidium tenue, two distinct types of cyanobacteria. Calcium spirulan, an extract obtained from Spirulina platen- sis, is a remarkable substance derived from these organisms
that exhibits robust antiviral properties [42]. Specific strains of cyanobacteria produce antifouling agents possessing anti­biotic attributes, like extracts from Lyngbya majuscule, which have been explored as possible reservoirs for antifoul­ing substances. Moreover, certain products originating from cyanobacteria showcase multifaceted therapeutic qualities [43]. For instance, Ulithiacyclamide and Patellamides A and C are recognized for their effectiveness against malaria and tumors, and for reversing resistance to multiple drugs [44]. These Gram-negative bacteria, classified as Cyanophyta, represent a useful source of innovative bioactive chemicals with fungicidal, anti-inflammatory, antibacterial, and anti­tumor properties, rendering them promising candidates for potential pharmaceutical uses [45].
Antibacterial (antibiotics) [34]
Anti MRSA (methicillin­resistant Staphylococcus aureus)
[35]
376 19 Marine Pharmacognosy
19.4.1.2 Marine Macroalgae
Macroalgae, also known as seaweeds, thrive in intertidal zones and tropical marine environments. These multicel­lular organisms display a diverse array of physical traits and morphologies and may be classified based on the pigments they produce for photosynthesis, such as red seaweed (Rhodophyta), green seaweed (Chlorophyta), and brown oceanic algae (Phaeophyta) [46] (Figure 19.2). Over 3 200 distinct chemicals have been extracted from macroalgae, with a significant proportion sourced from subtropical and tropical waters [47]. These chemicals have a diverse variety of therapeutic properties, encompassing anticancer, free radicle scavenger, antiviral agent, fouling-resistant, antithrombotic, antimicrobial, fungicidal, and anthelmin­thic properties [48, 49].
Red seaweeds are being explored for applications, such as anticoagulants, anthelmintics, and treatments for gastritis and diarrhea [50]. Green seaweeds have traditional uses, including applications as anthelmintics, astringents, and anti-gout remedies. Brown marine algae are utilized in the management of conditions like arthritis, high blood pres­sure, arteriosclerosis, menstruation issues, skin ailments, gastrointestinal ulcers, goiter, and sexually transmitted dis­eases, and they also serve as anticoagulants. Notably, the polysaccharides present in macroalgae, including ulvans from green seaweeds, alginates, fucans, laminarin from brown oceanic algae, and carrageenans and porphyrans from red seaweeds, have the capacity to elicit defense responses against plant pathogens [51].

19.4.2 Bioactive Compounds and Their Applications

Microalgae, autotrophic organisms found in diverse envi­ronments, produce various secondary metabolites known as “High-value Molecules” (HVMs). These HVMs have
therapeutic properties, including anticancer and antimi­crobial effects, making microalgae attractive for pharma­ceutical, cosmetic, and other industrial applications. Additionally, microalgae can coproduce pigments, pro­teins, polyunsaturated fatty acids (PUFAs), and antioxi­dants, expanding their potential uses in health-related products and across industries like food, cosmetics, energy, and pharmaceuticals [52].
19.4.2.1 Pigments
Macroalgae are capable of generating three primary groups of natural pigments, specifically chlorophylls, carotenoids, and phycobilins. Algae that have high concentrations of chlorophylls a and b usually exhibit green color, whereas the greenish-brown appearance in algae can be ascribed to the existence of fucoxanthin, a carotenoid. Furthermore, the red coloration in seaweed is a result of the existence of chlorophylls A, C, and D in association with phycobilins, comprising PE (a blue pigment) and PC (a red pigment) [53, 54].
Carotenoids have garnered increased interest due to their antioxidative attributes, prompting their incorpora­tion in dietary supplements, enriched food products, edible colorants, animal nutrition, pharmaceuticals, and cosmetic formulations. They hold promise in potentially mitigating the risk of cardiovascular diseases (CVDs), cancers, and various eye-related disorders [55].
Carotenoids, a class of lipophilic linear polyenes, may be particularly arranged in two major categories: carotenes (α, β, and γ carotene) and lycopenes (which have a cyclic struc­ture at the end of the chain, composed solely of carbon and hydrogen atoms), as well as xanthophylls or oxycarotenoids [53]. Green sea algae species include β-carotene, lutein, vio- laxanthin, neoxanthin, and zeaxanthin, whereas brown algae species have β-carotene, violaxanthin, pheophytins, and fucoxanthin. It is effective toward both Gram-positive
Figure 19.2 Marine macroalgae; red seaweeds (left) and brown marine algae (right) [46].
19.4 Marine Algae and Their Medicinal Potential 377
as well as Gram-negative bacteria [56, 57]. These com­pounds exhibit properties related to antioxidation, cancer prevention, inflammation reduction, obesity prevention, inhibition of angiogenesis, and neuroprotection.
19.4.2.1.1 Polyunsaturated Fatty Acids
PUFAs, specifically eicosapentaenoic acid (EPA) and doc­osahexaenoic acid (DHA), are commonly derived from fish oil. However, their usage is restricted due to their unpleasant taste and odor. As an alternative, microalgae like Tetraselmis sp. and Nannochloropsis oculata have gained prominence as abundant sources of PUFAs [58]. EPA and DHA are vital omega-3 fatty acids found in marine oils, renowned for their diverse health advan­tages; it include the impact on cardiovascular health, the coagulation process, blood platelets, endothelial structure and function, and the breakdown of lipoprotein [59]. Clinical studies using algal DHA have revealed a reduc­tion in blood triglyceride levels and possible cardiovascu­lar benefits [60].
EPA plays indispensable roles in cellular metabolism and holds a significant role in biological membranes. Healthy conditions, including lipid disorders, hyperten­sion, diabetes mellitus, and cerebrovascular illnesses, might be beneficiated from the absorption of omega-3 fatty acids, which includes EPA. Research performed on animal models has underscored the advantages of EPA for diabetic animals [61, 62]. DHA has a significant function in cerebral and vision development, and it also impacts the health of the cardiovascular system by being an essential component of the nervous system, the eye, and cardiac muscle. DHA algal oil, such as that from Schizochytrium sp., demonstrates a favorable safety pro-
file even at lower intake levels. Moreover, supplement­ing breastfeeding mothers with algal DHA supports infant brain development [63]. Both EPA and DHA have critical roles in resolving disorders, including dementia, Parkinson’s, Alzheimer’s, a skin disorder called psoria­sis, cancer, atherosclerosis, autoimmune diseases, such as rheumatoid arthritis, and inflammation-related con­ditions [56]. Animal experiments expresses the potential advantages of omega-3 fatty acids, including those from algal sources, in the management of Parkinson’s disease (PD) and other neurological disorders.
19.4.2.2 Proteins
Microalgae are considered to be prospective biological hubs for their high level of protein which, makes them ideal for protein synthesis. They serve as a valuable feed source for livestock and poultry and offer a nutritious option for human consumption. Notably, microalgal varie­ties like Arthrospira, Chlorella, Dunaliella salina, and Spirulina are known for their high protein content. Microalgal proteins have demonstrated anti-inflammatory and antitumor properties [64]. Phycobiliproteins derived from marine cyanobacteria and red seaweeds possess a diverse range of advantageous qualities, including antitu­mor, anti-inflammatory property, immunomodulatory, antioxidant, hepatoprotective, and neuroprotective effects. Furthermore, a recently discovered biomolecule known as mycosporine-like amino acids (MAAs), found extensively in oceanic creatures, such as microalgae, has demonstrated its effectiveness in countering photoaging in various skin types [65].
Some bioactive compounds from marine algae showing
different pharmacological action are listed in Table 19.2.
Table 19.2 Bioactive compounds from marine algae
Compound name Source Biological activity Health benefits References
Fucoxanthin Brown algae Suppressing McP-1 and enhancing
Spiralisone A Zonaria spiralis (brown
algae)
adrb3 and gluT4 expression in the mitochondria of white adipose tissue (WAT) increases fatty acid oxidation and induces the generation of heat in WAT via boosting the level of uncoupling protein1.
Exhibits inhibitory effects against neurological diseases by targeting CDK5/p25, CK1δ, and GSK3β kinases, also shows antibacterial activity against Gram-positive Bacillus subtilis.
Antidiabetic and antiobesity [66]
Antibacterial [67]
(Continued)
378 19 Marine Pharmacognosy
Table 19.2 (Continued)
Compound name Source Biological activity Health benefits References
Caulerpenyne Caulerpa taxifolia Toxicity observed in cultured cell
Phobasterone B Red seaeweed Antimicrobial activity against Bacillus
Caulerpin Caulerpa racemosa
(Green algae)
lines, including KB cells and hamster hepatocytes.
cereus, Streptococcus pneumoniae, and Candida albicans.
Stimulates the generation of NO by increasing the expression of iNOS at both the mRNA and protein ratios. Additionally, it promotes the transcription of mRNA for various cytokines, such as IL-1β, IL-6, IL-10, and TNF-α.
Anticancer [68]
Antimicrobial [69]
Immunostimulating impact through macrophage activation
[70]
Figure 19.3 Phylum porifera, sponges (left), and animalia (right) [73].

19.5 Marine Invertebrates and Its Bioactive

Marine invertebrates refer to those organisms inhabiting marine environments. The term “invertebrate” encom­passes all non-vertebrate animals within the chordate phy­lum. Invertebrates are characterized by the absence of a vertebral column, and some have developed protective fea­tures like shells or robust exoskeletons [71]. These creatures play crucial roles in marine ecosystems and often possess unique bioactive compounds that have garnered significant attention in fields, such as pharmaceuticals, biotechnology, and scientific research. The marine invertebrates most extensively researched for their bioactive compound poten­tial encompass sponges, cnidarians, molluscs, echinoderms, and ascidians [72]. There are some notable examples of sea invertebrates and their bioactive as follows:

19.5.1 Sponges (Phylum Porifera)

Marine sponge-like organisms are composed up of a jelly­like membrane wedged within two thin cellular sheets, as well as filaments formed of quartz, carbonates of calcium,
and a protein called spongin. In the 1950s, investigators found evidence of modified nucleotides in extracts from the Caribbean sponge (Cryptotethya crypta), highlighted the importance of secondary chemical compounds hav­ing biological activity from marine invertebrates [73] (Figure 19.3). This major achievement subsequently led to the production of cytarabine (Cytosar-U®), the first marine-based medicine accessible [74]. These compounds are mainly categorized into terpenes, alkaloids, lipids, and peptides. Half of these bioactive compounds exhibit cytotoxic effects against tumor cells, while around 14% display antimicrobial properties. Interestingly, certain marine natural products (MNPs) sourced from sponges have demonstrated potential in inhibiting essential enzymes and protein synthesis that contribute to the reg­ulation of cell cycles, cellular death induction, proteas­ome function, and protein phosphatase activity. For example, renieramycins, which were originally isolated from the colonial ascidian Ecteinascidia turbinata and sold as Yondelis, have been approved for the treatment of malignancies of ovary and metastatic soft tissue carcinoma [75]. This demonstrates their potential as main candidates for developing novel anticancer medicines.
19.5 Marine Invertebrates and Its Bioactive 379

19.5.2 Molluscs

Molluscs constitute a diverse group of marine inverte­brates, encompassing snails, clams, oysters, mussels, and squid (Figure 19.4). They serve as a vital source of suste­nance and economic value for humans, while also present­ing a valuable reservoir of bioactive compounds, including peptides, alkaloids, terpenes, and steroids [73]. These chemicals display a diversity of biological functions, such as antitumor, antibacterial, anti-inflammation property, and analgesic properties. Lignarenone B, is an example of a signaling compound released by molluscs. It activates by reducing glycogen synthase kinase 3 (GSK3) activity using both ATP selective and non-competitive allosteric path­ways. In addition, this chemical has the capability to enhance the synthesis of neuritic cells in initial cortex neu­rons cultures while having no adverse consequences on neurons. As a result, it offers an encouraging beginning for the design of prospective therapeutic medicines for neuro-
Figure 19.4 Molluscs: snail [73].
logical disorders such as AD. Dolastatins, found in both linear and cyclic forms, were initially identified in the sea hare Dolabella Auricularia. These are cytotoxic peptides functioning as mitotic inhibitors. They disrupt cell division by interfering with tubulin formation, ultimately triggering apoptosis in numerous cancerous cell lines. Dolastatins have exhibited significant promise in treating breast and liver cancers, solid tumors, and specific types of leukemia, thereby undergoing clinical evaluation for their anticancer properties [77, 78].

19.5.3 Echinoderms

The Echinodermata Phylum, the second-largest group of deuterostomes, distinguishes itself by the absence of any freshwater or terrestrial members. Echinoderms can be categorized into five clades: Echinoidea (including sea urchins), Holothuroidea (sea cucumbers), Crinoidea (sea lilies and feather stars), Asteroidea (sea stars and starfish), and Ophiuroidea (brittle stars) (Figure 19.5). Echinoderms are recognized for their synthesis of bioactive-glycosylated metabolic products, primarily characterized by steroidal and sulfated substances, saponins, and glycolipids [79]. They are known for their spiky skin and radial symmetry. Echinoderms yield a wide array of bioactive compounds, spanning peptides, alkaloids, saponins, and terpenes. These compounds possess diverse biological activities, encompassing anticancer, antimicrobial, anti-inflamma­tory, and wound-healing properties. Sea cucumbers, mem­bers of the Holothuroidea clade, are extensively spread in deep sea and benthic environments. The primary source of their bioactive components is the body wall, which consists mainly of polysaccharides and collagen [80].
Figure 19.5 Echinoderms: Starfish (left) and sea cucumber (right) [79].
380 19 Marine Pharmacognosy
Table 19.3 Bioactive compounds from marine invertebrates
Compound name Source Biological activity Health benefits References
Metachromin A (Sponges) Dactylospongia metachromia Inhibits the production of
Zampanolides B, C, and D Cacospongia mycofijinsis Antimitotic and anti-
Misszrtine A Aspergillus sp. Due to the presence of indole
Plakortides Plakortis halichondrioides Increased Ca
Latrunculin B Negombota magnifica Shows fungal activity for
Some bioactive compounds from marine invertebrates showing different pharmacological action are listed in Table 19.3.
HBV by virtue of the hydroquinone moiety and double bonds located at carbon positions 5 and 9 without causing cytotoxicity.
proliferative activity which shows nanomolar cytoxicity on HL-60 cell line.
nitrogen shows greater effect on its cytotoxicity activity.
2+
activity of sarcoplasmic reticulum.
aquaculture.
pumping
sampling location is crucial, as it determines the quality and type of compounds obtained. Factors like depth, water temperature, and geographic coordinates are considered.
19.6.2 Extraction Process and

19.6 Extraction Process and Characterization Techniques

19.6.1 Collecting and Processing of Marine Compounds

The collection of marine samples should adhere to the guidelines established by the United Nations Convention on Biological Diversity (CBD), which was initially introduced for signature during the Earth Summit in Rio de Janeiro on 5 June 1992, and officially came into force on 29 December
1993. Notably, there have been recent updates to the CBD, including the introduction of the “Nagoya Protocol.” If this protocol is ratified by the parties to the CBD, it will give legal binding status to the CBD’s terms. The CBD encourages a global commitment to biological variety protection, sustain­able exploitation of natural resources, and the equal sharing of benefits from genetic information.
Marine bioactive chemicals can be obtained from sev­eral kinds of marine creatures, including algae, bacteria, and marine mammals. Collection methods may include harvesting, fishing, or microbial culturing, depending on the source. Specific marine organisms are chosen for their bioactive compounds, such as algae for pigments or micro­organisms for enzymes and metabolites. The choice of
Characterization Techniques
Extraction is a critical initial step in the journey to harness the therapeutic potential of compounds originating from marine creatures. It is the process by which bioactive com­pounds are separated from the complex matrix of marine organisms. It allows scientists to isolate the specific com­pounds of interest, such as novel molecules with potential pharmaceutical applications. Effective extraction methods aim to preserve the bioactivity of the compounds. The goal is to obtain the compounds in their natural form, ensuring that their therapeutic properties remain intact. The extrac­tion process determines the quantity of bioactive com­pounds obtained. Efficient extraction methods maximize yield, making it possible to obtain sufficient quantities for further analysis and testing. Extracted compounds must be in a form suitable for analytical testing [86]. Extraction pre­pares the compounds for subsequent analysis, enabling researchers to characterize their chemical structures and assess their potential as pharmaceutical agents. The extracted compounds are subjected to biological assays to evaluate their potential as drugs. The quality of the extrac­tion process directly impacts the reliability and accuracy of these assessments [87]. Sustainable extraction practices are essential to minimize environmental impact. Responsible
Antiviral [81]
Macrolides [82]
Anticancer [83]
Cardiac relaxant [84]
Antifungal [85]