Sponge Research Articles

Equisetin protects from atherosclerosis in vivo by binding to STAT3 and inhibiting its activity

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.

Green synthesized extracts/Au complex of Phyllospongia lamellosa: Unrevealing the anti-cancer and anti-bacterial potentialities, supported by metabolomics and molecular modeling

The anti-cancer and anti-bacterial potential of the Red Sea sponge Phyllospongia lamellosa in its bulk (crude extracts) and gold nanostructure (loaded on gold nanaoparticles) were investigated. Metabolomics analysis was conducted, and subsequently, molecular modeling studies were conducted to explore and anticipate the P. lamellosa secondary metabolites and their potential target for their various bioactivities. The chloroformic extract (CE) and ethyl acetate extract (EE) of the P. lamellosa predicted to include bioactive lipophilic and moderately polar metabolites, respectively, were used to synthesize gold nanoparticles (AuNPs). The prepared AuNPs were characterized through transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV–vis spectrophotometric analyses. The cytotoxic activities were tested against MCF-7, MDB-231, and MCF-10A. Moreover, the anti-bacterial, antifungal, and anti-biofilm activity were assessed. Definite classes of metabolites were identified in CE (terpenoids) and EE (brominated phenyl ethers and sulfated fatty amides). Molecular modeling involving docking and molecular dynamics identified Protein-tyrosine phosphatase 1B (PTP1B) as a potential target for the anti-cancer activities of terpenoids. Moreover, CE exhibited the most powerful activity against breast cancer cell lines, matching our molecular modeling study. On the other hand, only EE was demonstrated to possess powerful anti-bacterial and anti-biofilm activity against Escherichia coli. In conclusion, depending on their bioactive metabolites, P. lamellosa-derived extracts, after being loaded on AuNPs, could be considered anti-cancer, anti-bacterial, and anti-biofilm bioactive products. Future work should be completed to produce drug leads.

Gene networks governing the response of a calcareous sponge to future ocean conditions reveal lineage-specific XBP1 regulation of the unfolded protein response.

Marine sponges are predicted to be winners in the future ocean due to their exemplary adaptive capacity. However, while many sponge groups exhibit tolerance to a wide range of environmental insults, calcifying sponges may be more susceptible to thermo-acidic stress. To describe the gene regulatory networks that govern the stress response of the calcareous sponge, Leucetta chagosensis (class Calcarea, order Clathrinida), individuals were subjected to warming and acidification conditions based on the climate models for 2100. Transcriptome analysis and gene co-expression network reconstruction revealed that the unfolded protein response (UPR) was activated under thermo-acidic stress. Among the upregulated genes were two lineage-specific homologs of X-box binding protein 1 (XBP1), a transcription factor that activates the UPR. Alternative dimerization between these XBP1 gene products suggests a clathrinid-specific mechanism to reversibly sequester the transcription factor into an inactive form, enabling the rapid regulation of pathways linked to the UPR in clathrinid calcareous sponges. Our findings support the idea that transcription factor duplication events may refine evolutionarily conserved molecular pathways and contribute to ecological success.

Total Synthesis and Antibacterial Activity of Marine Tris-indole Alkaloid Tulongicin A.

Bis-indole alkaloids from marine sponges are an intriguing class of natural products with a variety of activities. However, only a preliminary biological study of tulongicin A (5), a related previously isolated marine tris-indole alkaloid, has been conducted. In this study, we accomplished the first asymmetric total synthesis of 5 via the construction of an imidazoline-linked bis-indolylmethane skeleton using a Friedel-Crafts-type reaction. Our synthesis enabled a detailed study of the antibacterial profile of 5. Compound 5 displayed bactericidal activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains.

Streptomyces-Fungus Co-Culture Enhances the Production of Borrelidin and Analogs: A Genomic and Metabolomic Approach.

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22-derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC50 of 0.004 mg/mL and on spore germination with an EC50 of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications.

Identification of Axinellamines A and B as Anti-Tubercular Agents.

Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library (n = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation of the organic extract from this Haplosclerida sponge led to the purification of previously identified antimicrobial pyrrole alkaloids, axinellamines A (1) and B (2). The axinellamine compounds were found to have a 90% minimum inhibitory concentration (MIC90) of 18 µM and 15 µM, respectively. The removal of protein and complex carbon sources reduced the MIC90 of 1 and 2 to 0.6 and 0.8 µM, respectively. The axinellamines were not toxic to mammalian cells at 25 µM and significantly reduced the intracellular bacterial load by >5-fold. These data demonstrate that axinellamines A and B are effective anti-tubercular agents and promising targets for future medicinal chemistry efforts.

Silactins and Structural Diversity of Biosilica in Sponges.

Sponges (phylum Porifera) were among the first metazoans on Earth, and represent a unique global source of highly structured and diverse biosilica that has been formed and tested over more than 800 million years of evolution. Poriferans are recognized as a unique archive of siliceous multiscaled skeletal constructs with superficial micro-ornamentation patterned by biopolymers. In the present study, spicules and skeletal frameworks of selected representatives of sponges in such classes as Demospongiae, Homoscleromorpha, and Hexactinellida were desilicified using 10% HF with the aim of isolating axial filaments, which resemble the shape and size of the original structures. These filaments were unambiguously identified in all specimens under study as F-actin, using the highly specific indicators iFluor™ 594-Phalloidin, iFluor™ 488-Phalloidin, and iFluor™ 350-Phalloidin. The identification of this kind of F-actins, termed for the first time as silactins, as specific pattern drivers in skeletal constructs of sponges opens the way to the fundamental understanding of their skeletogenesis. Examples illustrating the biomimetic potential of sophisticated poriferan biosilica patterned by silactins are presented and discussed.

A novel marine-derived mitophagy inducer ameliorates mitochondrial dysfunction and thermal hypersensitivity in paclitaxel-induced peripheral neuropathy.

Mitochondrial dysfunction contributes to the pathogenesis and maintenance of chemotherapy-induced peripheral neuropathy (CIPN), a significant limitation of cancer chemotherapy. Recently, the stimulation of mitophagy, a pivotal process for mitochondrial homeostasis, has emerged as a promising treatment strategy for neurodegenerative diseases, but its therapeutic effect on CIPN has not been explored. Here, we assessed the mitophagy-inducing activity of 3,5-dibromo-2-(2',4'-dibromophenoxy)-phenol (PDE701), a diphenyl ether derivative isolated from the marine sponge Dysidea sp., and investigated its therapeutic effect on a CIPN model. Mitophagy activity was determined by a previously established mitophagy assay using mitochondrial Keima (mt-Keima). Mitophagy induction was further verified by western blotting, immunofluorescence, and electron microscopy. Mitochondrial dysfunction was analysed by measuring mitochondrial superoxide levels in SH-SY5Y cells and Drosophila larvae. A thermal nociception assay was used to evaluate the therapeutic effect of PDE701 on the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae. PDE701 specifically induced mitophagy but was not toxic to mitochondria. PDE701 ameliorated paclitaxel-induced mitochondrial dysfunction in both SH-SY5Y cells and Drosophila larvae. Importantly, PDE701 also significantly ameliorated paclitaxel-induced thermal hyperalgesia in Drosophila larvae. Knockdown of ATG5 or ATG7 abolished the effect of PDE701 on thermal hyperalgesia, suggesting that PDE701 exerts its therapeutic effect through mitophagy induction. This study identified PDE701 as a novel mitophagy inducer and a potential therapeutic compound for CIPN. Our results suggest that mitophagy stimulation is a promising strategy for the treatment of CIPN and that marine organisms are a potential source of mitophagy-inducing compounds.

A new 3,4-dinorsteroid from the marine sponge Cliona sp.

A new steroid, 2a-oxa-2-oxo-5β-hydroxy-3,4-dinor-24-methylcholesta-22E-ene (1), together with 10 known ones (2–11), was isolated from the marine sponge Cliona sp. The structures of these compounds were determined by the spectroscopic methods (UV, IR, MS, and NMR) and X-ray diffraction analysis. Compound 1 was the third example of 3,4-dinorsteroid with a hemiketal at C-5 that was isolated from the natural source. In addition, the antibacterial activities of these compounds were also evaluated. However, none of them exhibited significant inhibition effects.

Suberitolactams A-D and Suberitopyridines A-B: New γ-lactam and Pyridine Alkaloids Isolated from the South China Sea Sponge Pseudospongosorites suberitoides.

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1 N1 virus with IC50 values of 27.6 and 13.3 μM, respectively.

3D Spongin Scaffolds as Templates for Electro-Assisted Deposition of Selected Iron Oxides.

The skeletons of marine sponges are ancient biocomposite structures in which mineral phases are formed on 3D organic matrices. In addition to calcium- and silicate-containing biominerals, iron ions play an active role in skeleton formation in some species of bath sponges in the marine environment, which is a result of the biocorrosion of the metal structures on which these sponges settle. The interaction between iron ions and biopolymer spongin has motivated the development of selected extreme biomimetics approaches with the aim of creating new functional composites to use in environmental remediation and as adsorbents for heavy metals. In this study, for the first time, microporous 3D spongin scaffolds isolated from the cultivated marine bath sponge Hippospongia communis were used for electro-assisted deposition of iron oxides such as goethite [α-FeO(OH)] and lepidocrocite [γ-FeO(OH)]. The obtained iron oxide phases were characterized with the use of scanning electron microscopy, FTIR, and X-ray diffraction. In addition, mechanisms of electro-assisted deposition of iron oxides on the surface of spongin, as a sustainable biomaterial, are proposed and discussed.

The genomes of the aquarium sponges Tethya wilhelma and Tethya minuta (Porifera: Demospongiae)

Sponges (Phylum Porifera) are aquatic sessile metazoans found worldwide in marine and freshwater environments. They are significant in the animal tree of life as one of the earliest-branching metazoan lineages and as filter feeders play crucial ecological roles, particularly in coral reefs, but are susceptible to the effects of climate change. In the face of the current biodiversity crisis, genomic data is crucial for species conservation efforts and predicting their evolutionary potential in response to environmental changes. However, there is a limited availability of culturable sponge species with annotated high-quality genomes to further comprehensive insights into animal evolution, function, and their response to the ongoing global change. Despite the publication of a few high-quality annotated sponge genomes, there remains a gap in resources for culturable sponge species. To address this gap, we provide high quality draft genomes of the two congeneric aquarium species Tethya wilhelma and Tethya minuta, small ball-shaped demosponges that are easily maintained long-term in ex situ culture. As such, they offer promising opportunities as laboratory models to contribute to advancing our understanding of sponge biology and provide valuable resources for studying animal evolution, function, and responses to environmental challenges.

Gelatin nanoparticles loaded with 3-alkylpyridinium salt APS7, an analog of marine toxin, are a promising support in human lung cancer therapy

This study demonstrates the potential of gelatin nanoparticles as a nanodelivery system for antagonists of nicotinic acetylcholine receptors (nAChRs) to improve chemotherapy efficacy and reduce off-target effects. Too often, chemotherapy for lung cancer does not lead to satisfactory results. Therefore, new approaches directed at multiple pharmacological targets in cancer therapy are being developed. Following the activation of nAChRs (e.g. by nicotine), cancer cells begin to proliferate and become more resistant to chemotherapy-induced apoptosis. This work shows that the 3-alkylpyridinium salt, APS7, a synthetic analog of a toxin from the marine sponge Haliclona (Rhizoneira) sarai, acts as an nAChR antagonist that inhibits the pro-proliferative and anti-apoptotic effects of nicotine on A549 human lung adenocarcinoma cells. In this study, gelatin-based nanoparticles filled with APS7 (APS7-GNPs) were prepared and their effects on A549 cells were compared with that of free APS7. Both APS7 and APS7-GNPs inhibited Ca2+ influx and increased the efficacy of cisplatin chemotherapy in nicotine-stimulated A549 cells. However, significant benefits from APS7-GNPs were observed – a stronger reduction in the proliferation of A549 lung cancer cells and a much higher selectivity in cytotoxicity towards cancer cells compared with non-tumorigenic lung epithelial BEAS-2B cells.

Chemical Component Analysis of Marine Sponge Extract of Potentially Medicinal Based on Solvent Differences

Tracing and characterizing marine natural materials with special medicinal abilities is important to obtain new materials to enrich the diversity of drugs to treat particular diseases. The identification of the chemical components of sponges is interesting, considering the uniqueness and several other abilities possessed by sponges that are thought to have medicinal potential. Searching for chemical components in sponge extracts is suspected to contain secondary metabolic substances with medicinal potential. The study aimed to identify the chemical components of sponge extract with potential medicinal value based on differences in solvents. The first extract on the sponge Clathria (Thalysias) reinwardti Sp.1 (CTR) by maceration method using semi-polar solvents (methanol). The second extraction uses a separating funnel with two types of non-polar solvents (diethyl-ether and n-hexane). The chemical components of the three extracts were analyzed using a gas chromatography-mass spectrophotometer instrument. The identified chemical components of sponge extract generally belong to the class of free fatty acids and cholesterol. Investigation of identified compounds with medicinal value chemical components, for example, Cholestan-3.alpha.-ol, Ergosta-5, Hexadecanoic acid, 1-(2,6-Dichlorophenyl)-2-indolinone and Pyridine-3-carboxamide. Searching for chemical components with medicinal potential from sponge extracts is novelty research based on differences in solvents, a new method. Complementing the data from this research, it is necessary to carry out further and specific searches related to chemical components with medicinal properties, which can be carried out by chromatographic fractionation and testing the activity of the extract against bacteria. pathogens and parasitic fungi.

Biofouling sponges as natural eDNA samplers for marine vertebrate biodiversity monitoring

Environmental DNA (eDNA) analysis has now become a core approach in marine biodiversity research, which typically involves the collection of water or sediment samples. Yet, recently, filter-feeding organisms have received much attention for their potential role as natural eDNA samplers. While the indiscriminate use of living organisms as ‘sampling tools’ might in some cases raise conservation concerns, there are instances in which highly abundant sessile organisms may become a nuisance as biofouling on artificial marine structures. Here we demonstrate how a sea sponge species that colonizes the moorings of the world's largest curtain of hydroacoustic receivers can become a powerful natural collector of fish biodiversity information. By sequencing eDNA extracted from Vazella pourtalesii retrieved from moorings during routine biofouling maintenance, we detected 23 species of marine fish and mammals, compared to 19 and 15 species revealed by surface and bottom water eDNA respectively, and 28 species captured by groundfish survey in the surrounding area, which are more ecologically impactful and involve higher additional costs. Sponge-based species inventories proved at least as informative as those obtained by traditional survey methods, and are also able to detect seasonal differences in fish assemblages. We conclude that opportunistic sampling of marine sponge biofouling may become an efficient way to document and monitor biodiversity in our rapidly changing oceans.

Cytotoxic Activity and Molecular Docking Studies of the Fraction Containing Ergosta-14,22-dien-3-ol (3β, 5α, and 22E) from Dysidea avara Sponges

Background: Cancer is a global health burden, and the discovery of novel therapeutic agents remains a critical pursuit. Marine organisms, including sponges, have emerged as a promising source of structurally diverse natural products with potential anticancer properties. Objectives: In the present study, the cytotoxic activity of the fraction containing Ergosta-14,22-dien-3-ol (3β, 5α, and 22E), a steroid compound derived from Dysidea avara, was evaluated against Jurkat/E6-1 and Hek293 cells. Methods: Multiple analytical techniques, including column chromatography, TLC, and GC-MS, were used to isolate and identify the compound from marine sponges from the Persian Gulf. The XTT assay determined the cytotoxic activity and western blot for P53 expression in the Jurkat/ E6-1 cell line. The compound was also docked within the poly (ADP-ribose) polymerase-1 (PARP1) and E3 ubiquitin-protein ligase (MDM2) to investigate its potential mechanism of action. Furthermore, the pharmacological properties of the compound were predicted using PerADME, SwissADME, and Molinspiration tools. Results: The results showed that Ergosta-14,22-dien-3-ol (3β, 5α, and 22E) exhibited significant cytotoxic activity against Jurkat/E6-1 cells with an IC50 of 26.59 μg/mL. Western blotting analysis demonstrated a noticeable increase in the expression of P53 protein in cells treated with 50 and 100 µg/mL of the compound. In silico analysis revealed adequate binding energy against PARP1 and E3 MDM2 receptors. The compound also demonstrated favorable pharmacokinetic characteristics, specifically in absorption, distribution, metabolism, and excretion (ADME). Conclusions: Ergosta-14,22-dien-3-ol (3β, 5α, and 22E) has the potential to be developed as a promising anti-cancer agent.

Latitudinal distribution of freshwater sponge species across European Russia

This study provides original faunistic data on freshwater sponge dispersal across a huge territory of European Russia from north to south, highlighting the northern limits of thermophilic and north-adapted species. The holarctic species Ephydatia muelleri and, especially, Spongilla lacustris were predominant in northern areas, while the cosmopolitan Ephydatia fluviatilis and Eunapius fragilis were less prevalent. Moving to the south, E. fluviatilis took the lead. The distributional pattern of northern sponges aligns with literature data from North Europe, confirming the prevalence of the holarctic species in high latitudes. Tubella (=Trochospongilla) horrida, Eunapius carteri, and Radiospongilla cerebellata are considered to be thermophilic species that could not tolerate the conditions in northern regions. Notable findings include the extension of Eunapius carteri's known range and the first report of R. cerebellata within Russia, which is also the second record for Europe. Three potentially expected species were not found in the studied area, indicating regional rarity. We also provide molecular and morphological evidence for the synonymy of Spongilla arctica and Spongilla lacustris. Finally, we discuss the impacts of climate change and agricultural activities on northern and southern sponge habitats respectively.

3D printed scaffolds of biosilica and spongin from marine sponges: analysis of genotoxicity and cytotoxicity for bone tissue repair.

Biosilica (BS) and spongin (SPG) from marine sponges are highlighted for their potential to promote bone regeneration. Moreover, 3D printing is introduced as a technology for producing bone grafts with optimized porous structures, allowing for better cell attachment, proliferation, and differentiation. Thus, this study aimed to characterize the BS and BS/SPG 3D printed scaffolds and to evaluate the biological effects in vitro. The scaffolds were printed using an ink containing 4 wt.% of sodium alginate. The physicochemical characteristics of BS and BS/SPG 3D printed scaffolds were analyzed by SEM, EDS, FTIR, porosity, evaluation of mass loss, and pH measurement. For in vitro analysis, the cellular viability of the MC3T3-E1 cell lineage was assessed using the AlamarBlue® assay and confocal microscopy, while genotoxicity and mineralization potential were evaluated through the micronucleus assay and Alizarin Red S, respectively. SEM analysis revealed spicules in BS, the fibrillar structure of SPG, and material degradation over the immersion period. FTIR indicated peaks corresponding to silicon oxide in BS samples and carbon oxide and amine in SPG samples. BS-SPG scaffolds exhibited higher porosity, while BS scaffolds displayed greater mass loss. pH measurements indicated a significant decrease induced by BS, which was mitigated by SPG over the experimental periods. In vitro studies demonstrated the biocompatibility and non-cytotoxicity of scaffold extracts. .Also, the scaffolds promoted cellular differentiation. The micronucleus test further confirmed the absence of genotoxicity. These findings suggest that 3D printed BS and BS/SPG scaffolds may possess desirable morphological and physicochemical properties, indicating in vitro biocompatibility.

Ocean Acidification: Effects on Sponges

Approximately 30% of the carbon dioxide (CO2) released into the atmosphere has been absorbed by the world’s oceans. As CO2 emissions increase due to human activities so does the amount of CO2 absorbed by the oceans. Carbon dioxide lowers the pH of the ocean system, causing ocean acidification (OA). The effects of OA on economically and ecologically important aquatic species is a subject of interest. Sponges are important reef-associated species that provide shelter for fish and crustaceans in reef habitats and can also structure ecosystems through bioerosion, water filtration, and colonization of coral reef areas. This publication considers the effects of OA on marine sponges, with a focus on Florida’s coral reef.

Irciniaplysins A-D: New Psammaplysin Derivatives from Philippine Marine Sponge Ircinia sp.

Four new psammaplysin derivatives (1-4) with fatty acyl substituents, designated irciniaplysins A-D, and three known psammaplysins (5-7) were isolated from a marine sponge Ircinia sp. Their structures were elucidated using extensive spectroscopic analyses. The positions of the double bonds and the branch points of the fatty acyl side chains were determined by GC-MS analysis of their fatty acid methyl ester (FAME) derivatives. Irciniaplysins A (1) and B (2) contained an unusual long-chain fatty acyl substituent with a 5,9-diene unit. The isolated compounds were evaluated for their cytotoxic activity against the human colorectal carcinoma (HCT 116) cells, however, none of these compounds showed significant activity.