Toxins and Biologically Active Compounds from Microalgae, Volume 1

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Nostocspecies are producers of structurally and functionally diverse natural biological activities such as antibacterial, antiviral, anticancer, antitumor, algicide, antifungal, enzyme inhibiting, immunostimulant, antiplatelet aggregation, cytotoxic and antiplasmodium activities.

Most of the isolated substances from the alga belong to groups of hydrocarbons such as phytane; lipids such as sterol, esters, waxes and free sterols; fatty acids such as dioic acids; derivatives of amino acids such as indoleacetic acid and anatoxin A; terpenoids and aromatic compounds such as diterpenoid and anthraquinone; boron-containing macrocycles such as borophycin; arsenolipids such as dimethylarsenic acid; mycosporine-like amino acids such as shinorine and scytonemin; lipopeptides such as cryptophycin-1 and polyketides and several carotenoids; amides, alkaloids, peptides, monosaccharides and polysaccharides.

Some extracellular metabolites secreted by cyanobacteria function as toxins or allelochemicals. Apart from these cytotoxic metabolites e. This article provides an overview of bioactive compounds produced by Nostocspecies. Skip to main content Skip to main navigation menu Skip to site footer. Motilal Vigyan Mahavidyalaya, Bhopal M. India Abstract Recently microalgae have become commercially important because of novel compounds of potential medicinal value. References 1. Parsiguine, a novel antimicrobial substance from Fischerella ambigua. Comparison of light and dark nitrogenase activity in selected soil cyanobacteria.

Folia Microbiol. Browitzka MA. Microalgae as sources of pharmaceuticals and other biologically active compounds. New antibacterial metabolites from the cyanobacterium Nostoc commune. EAWAG b.

Associated Data

Nostofungicidine, an antifungal lipopeptide from the field-grown terrestrial blue-green alga Nostoc commune. Tetrahedron Letters 39 22 ; Biological effects of tolytoxin 6-hydroxyomethylscytophycin b , a potent bioactive metabolite from cyanobacteria. Bioactive natural products from bluegreen algae. Screening cultured marine microalgae for anticancer-type activity.

15 Filtering Microalgae

Phycol, ; 6: Isolation, structure determination, and biological activity of Lyngbya majuscule. Isolation, identification and determination of the absolute configuration of fischerellin B. A new algicide from the freshwater cyanobacterium Fischerella muscicola Thuret. Tetrahedron Lett. A Novel monogalactosylacylglycerol with inhibitory effect on platelet aggregation from the cyanophyceae Oscillatoria rosea. Associated Data Supplementary Materials marinedrugss Abstract The study of marine natural products for their bioactive potential has gained strength in recent years.

Keywords: bioprospecting, blue biotechnology, marine microalgae, bioactive compound, drug discovery, marine natural products. Introduction We are in a renaissance period for natural product discovery and their potential societal impact as a source of therapeutic drugs is popular [ 1 ]. Results and Discussion 2. Microalgae Cultures and Extracts Preparation Clonal cultures of 33 strains that include species of Phyla Dinophyta, Heterokontophyta, Haptophyta, and Chlorophyta were carried out to a medium-scale level to a final volume of 15 L for each strain.

Biological Evaluation Extracts from biomass and cell free culture medium obtained for 32 strain batches and from biomass of Scrippsiella trochoidea were screened in order to determine their biological properties. Open in a separate window. Figure 1. Figure 2. Figure 3. Figure 4. Figure 5.


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Materials and Methods 3. Conclusions In summary, a bioprospecting study on 33 microalgae strains was carried out.


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Figure 6. Click here for additional data file. Author Contributions C. Conflicts of Interest The authors declare no conflicts of interest. References and Note 1. Molinski T. All natural: The renaissance of natural products chemistry. Drug development from marine natural products. Drug Discov. Martins A. Marketed marine products in the pharmaceutical and cosmeceutical industries: Tips for success. Newman D. Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development.

Blunt J. Marine natural products.

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Kiuru P. Exploring marine resources for bioactive compounds. Planta Med. Michalak I. Algae as production systems of bioactive compounds. Life Sci. Bhatia P. Role of marine bioprospecting contracts in developing access and benefit sharing mechanism for marine traditional knowledge holders in the pharmaceutical industry. Global Ecol. Bekendorff K. Potential conservation benefits and problems associated with bioprospecting in the marine environment. In: Lunney D. A Zoological Revolution. Querellou J. European Science Foundation; Beernem, Belgium: Abid F.

Omics approaches in marine biotechnology: The treasure of ocean for human betterments. In: Barh D. Volume 1. Academic Press; Berlin, Germany: Sieg R. Chemical ecology of the marine plankton. Biotechnological significance of toxic marine dinoflagellates. Abida H.

Bioprospecting Marine Plankton. Keller M. Media for the culture of oceanic ultraphytoplankton. Harrison P. Marine culture media. In: Andersen R. Algal Culturing Techniques. Bravo I. Toxin composition of the toxic dinoflagellate Prorocentrum lima isolated from different locations along the Galician coast NW Spain Toxicon. Nagai H. Antimicrobial activities of polyether compounds of dinoflagellate origins.

Lillsunde K. Bioactive cembrane derivatives from the Indian Ocean soft coral, Sinularia kavarattiensis. Pisapia F. Maitotoxin-4, a novel MTX analog produced by Gambierdiscus excentricus. Ianora A. Copepod egg production and hatching success is reduced by maternal diets of a non-neurotoxic strain of the dinoflagellate Alexandrium tamarense.

Paasche E. In an effort to address this complication, neurite outgrowths either axonal or dendritic in response to applied compounds have recently been proposed as a more accurate distinction between true neurotoxins and cytotoxins in an in-vitro testing environment. Due to the significant inaccuracies associated with this process, however, it has been slow in gaining widespread support. Though diverse in chemical properties and functions, neurotoxins share the common property that they act by some mechanism leading to either the disruption or destruction of necessary components within the nervous system.

Neurotoxins, however, by their very design can be very useful in the field of neuroscience.

Neurotoxin - Wikipedia

As the nervous system in most organisms is both highly complex and necessary for survival, it has naturally become a target for attack by both predators and prey. As venomous organisms often use their neurotoxins to subdue a predator or prey very rapidly, toxins have evolved to become highly specific to their target channels such that the toxin does not readily bind other targets [28] see Ion Channel toxin s.

As such, neurotoxins provide an effective means by which certain elements of the nervous system may be accurately and efficiently targeted. An early example of neurotoxin based targeting used radiolabeled tetrodotoxin to assay sodium channels and obtain precise measurements about their concentration along nerve membranes. As neurotoxins are compounds which adversely affect the nervous system, a number of mechanisms through which they function are through the inhibition of neuron cellular processes.

These inhibited processes can range from membrane depolarization mechanisms to inter-neuron communication. By inhibiting the ability for neurons to perform their expected intracellular functions, or pass a signal to a neighboring cell, neurotoxins can induce systemic nervous system arrest as in the case of botulinum toxin , [13] or even nervous tissue death. Curare [37]. JWH [39]. Tetrodotoxin TTX is a poison produced by organisms belonging to the Tetradontidae order , which includes the puffer fish , ocean sunfish , and porcupine fish.

Common symptoms of TTX consumption include paraesthesia often restricted to the mouth and limbs , muscle weakness, nausea , and vomiting [49] and often manifest within 30 minutes of ingestion. This inhibition largely affects a susceptible subset of sodium channels known as TTX-sensitive TTX-s , which also happens to be largely responsible for the sodium current that drives the depolarization phase of neuron action potentials. TTX-resistant TTX-r is another form of sodium channel which has limited sensitivity to TTX, and is largely found in small diameter axons such as those found in nociception neurons.

This results in an increased effective threshold of required excitatory signals in order to induce an action potential in a postsynaptic neuron. Though assisted ventilation may increase the chance of survival after TTX exposure, there is currently no antitoxin. The use of the acetylcholinesterase inhibitor Neostigmine or the muscarinic acetylcholine antagonist Atropine which will inhibit parasympathetic activity , however, can increase sympathetic nerve activity enough to improve the chance of survival after TTX exposure.

Tetraethylammonium TEA is a compound that, like a number of neurotoxins, was first identified through its damaging effects to the nervous system and shown to have the capacity of inhibiting the function of motor nerves and thus the contraction of the musculature in a manner similar to that of curare. It has been hypothesized that the ability for TEA to inhibit potassium channels is derived from its similar space-filling structure to potassium ions. Chlorotoxin Cltx is the active compound found in scorpion venom, and is primarily toxic because of its ability to inhibit the conductance of chloride channels.

Similar to botulinum toxin, Cltx has been shown to possess significant therapeutic value. Evidence has shown that Cltx can inhibit the ability for gliomas to infiltrate healthy nervous tissue in the brain, significantly reducing the potential invasive harm caused by tumors. Conotoxins represent a category of poisons produced by the marine cone snail, and are capable of inhibiting the activity of a number of ion channels such as calcium, sodium, or potassium channels.

It has been shown that capsaicin active compound responsible for heat in chili peppers can bind the TRPV1 receptor expressed on cholinergic neurons and inhibit the toxic effects of BTX. Tetanus neurotoxin TeNT is a compound that functionally reduces inhibitory transmissions in the nervous system resulting in muscular tetany. TeNT is similar to BTX, and is in fact highly similar in structure and origin; both belonging to the same category of clostridial neurotoxins. Though both toxins inhibit vesicle release at neuron synapses, the reason for this different manifestation is that BTX functions mainly in the peripheral nervous system PNS while TeNT is largely active in the central nervous system CNS.

Neurotoxic behavior of aluminum is known to occur upon entry into the circulatory system , where it can migrate to the brain and inhibit some of the crucial functions of the blood brain barrier BBB.

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Though the metal is known to be neurotoxic, effects are usually restricted to patients incapable of removing excess ions from the blood, such as those experiencing renal failure. Diethylmercury and dimethylmercury are considered some of the most potent neurotoxins ever discovered. Investigations into anatoxin- a , also known as "Very Fast Death Factor", began in following the deaths of cows that drank from a lake containing an algal bloom in Saskatchewan, Canada.

Toxic effects from anatoxin- a progress very rapidly because it acts directly on the nerve cells neurons. The progressive symptoms of anatoxin- a exposure are loss of coordination, twitching , convulsions and rapid death by respiratory paralysis. The nerve tissues which communicate with muscles contain a receptor called the nicotinic acetylcholine receptor.

Stimulation of these receptors causes a muscular contraction. The anatoxin- a molecule is shaped so it fits this receptor, and in this way it mimics the natural neurotransmitter normally used by the receptor, acetylcholine. Once it has triggered a contraction, anatoxin- a does not allow the neurons to return to their resting state, because it is not degraded by cholinesterase which normally performs this function.

As a result, the muscle cells contract permanently, the communication between the brain and the muscles is disrupted and breathing stops. When it was first discovered, the toxin was called the Very Fast Death Factor VFDF because when it was injected into the body cavity of mice it induced tremors, paralysis and death within a few minutes.

In , the structure of VFDF was determined as a secondary, bicyclic amine alkaloid , and it was renamed anatoxin- a. Bungarotoxin is a compound with known interaction with nicotinic acetylcholine receptors nAChRs , which constitute a family of ion channels whose activity is triggered by neurotransmitter binding. Additionally, different forms of bungarotoxin may be useful for studying inhibited nAChRs and their resultant calcium ion flow in different systems of the body. Caramboxin CBX is a toxin found in star fruit Averrhoa carambola. Individuals with some types of kidney disease are susceptible to adverse neurological effects including intoxication, seizures and even death after eating star fruit or drinking juice made of this fruit.

Caramboxin is a new nonpeptide amino acid toxin that stimulate the glutamate receptors in neurons. Caramboxin is an agonist of both NMDA and AMPA glutamatergic ionotropic receptors with potent excitatory, convulsant, and neurodegenerative properties.

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The term " curare " is ambiguous because it has been used to describe a number of poisons which at the time of naming were understood differently from present day understandings. In the past the characterization has meant poisons used by South American tribes on arrows or darts , though it has matured to specify a specific categorization of poisons which act on the neuromuscular junction to inhibit signaling and thus induce muscle relaxation.

Normally, these receptor channels allow sodium ions into muscle cells to initiate an action potential that leads to muscle contraction. By blocking the receptors, the neurotoxin is capable of significantly reducing neuromuscular junction signaling, an effect which has resulted in its use by anesthesiologists to produce muscular relaxation. Arsenic is a neurotoxin commonly found concentrated in areas exposed to agricultural runoff , mining , and smelting sites Martinez-Finley One of the effects of arsenic ingestion during the development of the nervous system is the inhibition of neurite growth [87] which can occur both in PNS and the CNS.

The mechanism of this cytotoxicity functions through arsenite-induced increases in intracellular calcium ion levels within neurons, which may subsequently reduce mitochondrial transmembrane potential which activates caspases , triggering cell death. Lithium administration has shown promise, however, in restoring some of the lost neurofilament motility. Ammonia toxicity is often seen through two routes of administration, either through consumption or through endogenous ailments such as liver failure. This cerebral edema can be the result of nervous cell remodeling. As a consequence of increased concentrations, ammonia activity in-vivo has been shown to induce swelling of astrocytes in the brain through increased production of cGMP Cyclic Guanosine Monophosphate within the cells which leads to Protein Kinase G-mediated PKG cytoskeletal modifications.

Importantly, the toxic effects of ammonia on astrocyte remodeling can be reduced through administration of L-carnitine. This mitochondrial transition is a direct result of glutamine activity a compound which forms from ammonia in-vivo. Lead is a potent neurotoxin whose toxicity has been recognized for at least thousands of years. As a neurotoxin, ethanol has been shown to induce nervous system damage and affect the body in a variety of ways. Among the known effects of ethanol exposure are both transient and lasting consequences. Some of the lasting effects include long-term reduced neurogenesis in the hippocampus , [98] [99] widespread brain atrophy, [] and induced inflammation in the brain.

One significant example of reduced inter-neuron communication is the ability for ethanol to inhibit NMDA receptors in the hippocampus, resulting in reduced long-term potentiation LTP and memory acquisition. It has, additionally, been shown that ethanol directly reduces intracellular calcium ion accumulation through inhibited NMDA receptor activity, and thus reduces the capacity for the occurrence of LTP. In addition to the neurotoxic effects of ethanol in mature organisms, chronic ingestion is capable of inducing severe developmental defects.

Evidence was first shown in of a connection between chronic ethanol intake by mothers and defects in their offspring. The magnitude of ethanol neurotoxicity in fetuses leading to fetal alcohol syndrome has been shown to be dependent on antioxidant levels in the brain such as vitamin E.

Toxins and Biologically Active Compounds from Microalgae, Volume 1

The severity of these effects is directly dependent upon the amount and frequency of ethanol consumption by the mother, and the stage in development of the fetus. This occurs almost exclusively in dopaminergic neurons of the substantia nigra , resulting in the presentation of permanent parkinsonism in exposed subjects 2—3 days after administration. Unlike most common sources of neurotoxins which are acquired by the body through ingestion, endogenous neurotoxins both originate from and exert their effects in-vivo. Additionally, though most venoms and exogenous neurotoxins will rarely possess useful in-vivo capabilities, endogenous neurotoxins are commonly used by the body in useful and healthy ways, such as nitric oxide which is used in cell communication.

Though nitric oxide NO is commonly used by the nervous system in inter-neuron communication and signaling, it can be active in mechanisms leading to ischemia in the cerebrum Iadecola The neurotoxicity of NO is based on its importance in glutamate excitotoxicity, as NO is generated in a calcium-dependent manner in response to glutamate mediated NMDA activation, which occurs at an elevated rate in glutamate excitotoxicity.

Glutamate, like nitric oxide, is an endogenously produced compound used by neurons to perform normally, being present in small concentrations throughout the gray matter of the CNS. This toxicity can be both a result of direct lethality of glutamate on neurons and a result of induced calcium flux into neurons leading to swelling and necrosis.

Dopamine is an endogenous compound that is used as a neurotransmitter to modulate reward expectation. Dopamine kills dopamine-producing neurons by interfering with the electron transport chain in neurons. This interference results in an inhibition of cellular respiration , leading to neuron death. From Wikipedia, the free encyclopedia. For the scientific journal, see Neurotoxicology journal. Jean; Paiva, Michael Alcoholism: Clinical and Experimental Research. Strang, and Arthur J. Alcohol and Alcoholism. Nazmul; Rashid, A K M.

Mamunur; Mamun, A. Al; Khaliduzzaman, S. Singapore Medical Journal. Angewandte Chemie International Edition. Enid Adams, Michael E. Trends in Neurosciences. Arnon, Stephen S. The Journal of the American Medical Association. Aschner, M.

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