Marine Drugs最新文献

{"title":"The Brown Algal Phlorotannin Dieckol Attenuates Amyloid-β Oligomer-Induced Oxidative DNA Damage and Senescence-like Stress in Human Neuron-like Cells.","authors":"Yu-Ru Lee, Mei Chou Lai, Yu-Shun Tzeng, I-Min Liu","doi":"10.3390/md24090320","DOIUrl":"10.3390/md24090320","url":null,"abstract":"<p><p>Amyloid-β oligomers (AβOs) induce oxidative and genomic stress that may promote neuronal senescence-like alterations in Alzheimer's disease. Dieckol, a brown algal phlorotannin, has antioxidant and neuroprotective properties, but its effects on AβO-induced senescence-like stress remain unclear. Differentiated SH-SY5Y cells were pretreated with dieckol (10-50 μmol/L) or the receptor for advanced glycation end products (RAGE) antagonist azeliragon (100 μmol/L) for 24 h, followed by AβO (20 μmol/L) exposure for 24 h. Dieckol concentration-dependently preserved cell viability, as indirectly assessed by the MTT assay and reduced mitochondrial superoxide accumulation. Dieckol also decreased senescence-associated β-galactosidase positivity, H3K9me2/3-associated chromatin remodeling, and interleukin-1β, interleukin-6, and tumor necrosis factor-α secretion while partially restoring telomerase activity. This restoration was consistent with improved cellular stress resilience in the differentiated neuron-like model. Furthermore, dieckol reduced 8-hydroxy-2'-deoxyguanosine and γ-H2AX accumulation and attenuated ATM-Chk2-p53 DNA damage response signaling. Azeliragon elicited broadly similar responses; however, these similarities do not establish RAGE dependence or a shared mechanism of action. Collectively, dieckol concurrently attenuated mitochondrial oxidative stress, DNA damage response signaling, and senescence-associated alterations. Although these parallel effects support a possible relationship among these processes, their causal and temporal relationships remain to be established.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomedical Potential of the Deep-Sea Vent Mussel <i>Bathymodiolus azoricus</i>: Integrating Immunity, Bioadhesion, Biomineralization, and Targeted Transcriptomic Reanalysis.","authors":"Raul Bettencourt, Rui L Reis, Tiago H Silva","doi":"10.3390/md24090318","DOIUrl":"10.3390/md24090318","url":null,"abstract":"<p><p>The deep sea harbors a substantial proportion of the ocean's unexplored biological and chemical diversity, while hydrothermal vent ecosystems expose resident organisms to unusual combinations of hydrostatic pressure, steep chemical gradients, reduced compounds, and elevated metal concentrations. This Review examines the deep-sea vent mussel <i>Bathymodiolus azoricus</i>, a dominant species at Mid-Atlantic Ridge hydrothermal fields, as a source of biological mechanisms and molecular systems with potential biomedical relevance. We integrate three areas that have largely developed separately in the literature: innate immunity and host-symbiont interactions, mussel-derived wet adhesion and byssal structural proteins, and shell biomineralization and repair. These published observations are complemented by targeted reanalyses of legacy and more recent <i>B. azoricus</i> transcriptomic resources, used here as supporting transcriptomic evidence for molecular families relevant to these themes rather than as standalone genome-scale transcriptomic studies. Particular attention is given to mussel foot proteins and byssal collagens as candidate templates for wet-tissue adhesives and structural biomaterials, and to shell-derived calcium carbonate as a potential precursor for calcium-phosphate-based materials. We further advance a specific, testable hypothesis-long-term exposure to the metal-rich hydrothermal vent environment may have influenced the metal-binding chemistry of <i>B. azoricus</i> adhesive and structural proteins, potentially generating functional properties distinct from those of shallow-water mytilids. This possibility is biologically plausible in light of established DOPA-metal coordination mechanisms in mussel adhesion, but no direct comparative measurements of Fe³⁺-binding affinity, metal-mediated cross-linking, or adhesive performance currently demonstrate such an advantage in <i>B. azoricus</i>. The species should therefore be regarded not as a proven source of superior vent-adapted biomaterials, but as a well-suited experimental system in which immunity, bioadhesion, biomineralization, and environmental adaptation converge to generate specific hypotheses for biomedical discovery. Comparative functional studies, protein-level validation of transcript-derived candidates, and improved molecular characterization of foot and mantle tissues will be required to test these possibilities.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cembrane- and Casbane-Type Diterpenes from the South China Sea Soft Coral <i>Sinularia nanolobata</i>.","authors":"Yao Dong, Xiao Xiao, Li-Gong Yao, Lin-Fu Liang, Song-Wei Li, Yue-Wei Guo","doi":"10.3390/md24090317","DOIUrl":"10.3390/md24090317","url":null,"abstract":"<p><p>Five new cembrane-type diterpenes (<b>1</b>-<b>5</b>), one new casbane-type diterpene (<b>7</b>), and ten known related ones (<b>6</b>, <b>8</b>-<b>16</b>) were isolated from the South China Sea soft coral <i>Sinularia nanolobata</i>. The structures of new compounds were elucidated through comprehensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations, and comparison with the reported spectroscopic data of known analogs. Structurally, compounds <b>2</b>-<b>5</b> featured rare five- to seven-membered oxygen-containing heterocyclic rings with diverse joints, reflecting remarkable chemical diversity of secondary metabolites. In bioassays, all isolates were evaluated for their cytotoxic and anti-inflammatory effects. Although no significant cytotoxic or anti-inflammatory activity was observed, the structural novelty of these compounds expands the chemical diversity of this class of natural products, providing valuable leads for further structural modifications and biological investigations.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Genome Mining of <i>Jiangella</i> sp. GA3 from Turtle-Ingested Plastic Reveals Conserved Biosynthetic Gene Clusters.","authors":"Ruggero Baviera, Fanny Claire Capri, Paola Galluzzo, Rosa Alduina","doi":"10.3390/md24090319","DOIUrl":"10.3390/md24090319","url":null,"abstract":"<p><p>Rare actinobacteria are promising sources of specialized metabolites, yet genome mining still prioritizes genomes encoding many biosynthetic gene clusters (BGCs) rather than clusters that are distant from characterized chemistry. Here, we describe the isolation of a novel <i>Jiangella</i> strain reported from a marine, animal-associated plastisphere and place its biosynthetic repertoire in the context of the whole genus, providing a genome-based prioritization of candidate biosynthetic targets. Digital DNA-DNA hybridization (57.8%) and OrthoANIu (94.65%) values against its closest relative, <i>J. alba</i> DSM 45237ᵀ, support its assignment as a candidate novel species, although formal species description will require additional phenotypic and chemotaxonomic characterization. antiSMASH predicted twelve BGCs, within the range observed across the genus (7-13), of which only one matched a characterized pathway, and the Biosynthetic Novelty Index of the genome was 865.3, the fourth highest among the twelve genomes analyzed. Across these genomes, 124 BGCs grouped into 70 gene cluster families, 74% of them strain-specific. Two families without any characterized representative, a lasso-peptide family and a RiPP recognition element-containing family, were instead conserved across a subclade, down to nearly identical precursor peptides. No antimicrobial activity was detected under the conditions tested. Genus-wide comparison therefore identifies conserved yet uncharacterized families as rational priorities that cluster counts alone would miss.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Antihyperlipidemic Activity of Marine Polysaccharides.","authors":"Yongxuan Liu, Haowei Liu, Dan Li, Shengzhou Ma, Chunxia Li","doi":"10.3390/md24090315","DOIUrl":"10.3390/md24090315","url":null,"abstract":"<p><p>Hyperlipidemia is a chronic metabolic disorder in humans, contributing to the onset of cardiovascular diseases (CVDs) that remain the leading cause of death worldwide. Current clinical antihyperlipidemic agents are often accompanied by diverse adverse side effects. Therefore, developing safer novel lipid regulators is an urgent and challenging task. Marine polysaccharides exhibit remarkable antihyperlipidemic activity owing to their distinctive physicochemical properties, multi-target mechanisms, and system-level modulation. This review systematically summarizes recent progress regarding the antihyperlipidemic efficacy of marine polysaccharides and provides comprehensive insights into their sources, structural features, structure-activity relationships, mechanisms of action, and application potential. Furthermore, this review also highlights the existing limitations and challenges in translational research of marine polysaccharides, and puts forward future research directions to advance marine polysaccharides into safe, effective, and sustainable natural therapeutics for hyperlipidemia.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrocarpane-Type Sesquiterpenes from <i>Laurencia microcladia</i>.","authors":"Adrián Gutiérrez-Cepeda, Jorge J Cabrera-Trujillo, José J Fernández, Antonio Hernández-Daranas, Manuel Norte, María L Souto","doi":"10.3390/md24090316","DOIUrl":"10.3390/md24090316","url":null,"abstract":"<p><p>Seven undescribed sesquiterpenes featuring an uncommon macrocarpane skeleton, laurocarpanes A-G (<b>1</b>-<b>7</b>), were isolated from specimens of <i>Laurencia microcladia</i> collected in Fuerteventura, the Canary Islands. The identification of these macrocarpane-type metabolites is of particular interest from both chemical and chemotaxonomic perspectives, as it highlights distinctive biosynthetic capabilities within the studied species and further expands current knowledge regarding the distribution of this uncommon structural class in marine organisms. Their structures and configurational assignments were determined by a comprehensive NMR study, high-resolution mass spectrometry, and coupling constant evaluations. A biosynthetic model was proposed linking the assembly of the macrocarpane skeleton directly to an (<i>S</i>)-<i>β</i>-bisabolene monocyclic precursor, with the process mediated by vanadium-dependent bromoperoxidase (V-BPO). The plausibility of the proposed biogenetic formation of laurocarpanes A-G (<b>1</b>-<b>7</b>) was assessed through Density Functional Theory (DFT) calculations.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization and Intra-Laboratory Validation of the Neuro-2a Assay for Tetrodotoxin Detection in Mussels.","authors":"Alessandra D'Arelli, Silvio Sosa, Sonia Dall'Ara, Monica Cangini, Michela Carlin, Pietro Antonelli, Aurora Dall'Occo, Nicolas Scapin, Giuseppe Arcangeli, Carmen Losasso, Aurelia Tubaro, Marco Pelin","doi":"10.3390/md24090314","DOIUrl":"10.3390/md24090314","url":null,"abstract":"<p><p>Tetrodotoxin (TTX) is a potent marine neurotoxin responsible for severe seafood poisoning in humans, characterized by neurological symptoms that may be fatal. Originally identified as a natural contaminant of pufferfish (Tetraodontidae family), over the last few years TTX and its analogs have also been detected in other edible marine organisms, including mollusks, gastropods and crustaceans. Consequently, there is a need for rapid, sensitive, and reliable methods for TTX detection in seafood. In this study, a functional assay based on the use of mouse neuroblastoma Neuro-2a cells has been optimized and characterized for TTX detection in mussels. The assay is based on the toxin's ability to block voltage-gated sodium channels, thereby counteracting the sodium-dependent cytotoxicity induced by veratridine and ouabain. The linear range of the TTX standard curve fell between 0.44 and 33 ng/mL, with limits of TTX detection (LOD) and quantitation (LOQ) of 0.132 ng/mL and 0.439 ng/mL, respectively, and good intra- and inter-day repeatability (RSDr= 15 and 11%, respectively). The assay also detected saxitoxin, which shares the same mechanism of action as TTX, but was less sensitive towards 4,9-anhydro-TTX. The minimum mussel extract dilution of 1:100 did not result in matrix-related interference, allowing accurate TTX quantitation, with a LOQ of 0.54 µg TTX equivalents/kg mussel meat. Given its sensitivity, the optimized Neuro-2a assay represents a promising tool for toxicity-based TTX quantitation in mussels before their consumption.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposed Biosynthesis and Molecular Targets of Manzamine Alkaloids from <i>Acanthostrongylophora ingens</i> (Phylum Porifera: Class Demospongiae).","authors":"Novriyandi Hanif, Ritha Lusian Karuwal, Muhammad Naufal Khotmi Ramadhan Ashari Jaya Sudrajat, Didik Huswo Utomo, Gibral Abdul Khalik, Heri Yanti, Lik Tong Tan, Nicole J de Voogd, Anggia Murni, Junichi Tanaka","doi":"10.3390/md24090313","DOIUrl":"10.3390/md24090313","url":null,"abstract":"<p><p>Manzamine alkaloids are a structurally diverse class of marine-derived alkaloids that have attracted considerable interest because of their complex polycyclic architectures, diverse biological activities, and distinctive biosynthetic features. The Indonesian marine sponge <i>Acanthostrongylophora ingens</i> is a particularly rich source of these alkaloids, providing an opportunity to further explore their chemical diversity, biosynthetic relationships, and biological properties. Detailed analyses of LC-HR-ESI-MS/MS and molecular networking were performed on EtOAc layers obtained from H₂O/EtOAc partitioning of methanolic extracts of the marine sponge, <i>Acanthostrongylophora ingens</i>, collected from Raja Ampat (Southwest Papua), the Thousand Islands reef complex (Jakarta Special Region), Spermonde Archipelago (South Sulawesi), and Sangiang Island (Banten). This approach revealed the presence of both known and new manzamine alkaloids, along with their possible precursors and structural modifications, thereby supporting the proposed biosynthetic origin of these alkaloids. In addition, three flexible cytotoxic manzamine alkaloids, namely (+)-manzamine A hydrochloride (<b>1</b>), (+)-manzamine B (<b>2</b>), and (+)-32,33-dihydro-31-hydroxymanzamine A (<b>3</b>), were purified and their relative configurations determined using quantum mechanic NMR-based calculations and validated by X-ray analysis. (+)-Manzamine A hydrochloride (<b>1</b>) displayed the most potent cytotoxic activities against <i>Artemia salina</i> larvae (LC₅₀ value of 0.041 ± 0.012 µM) and HEK293T cells (IC₅₀ value of 0.599 ± 0.057 µM). The potent cytotoxic activity suggested the importance of azocine ring (<i>Z</i>-olefin at C32-C33) in <b>1</b>. Molecular mechanisms of <b>1</b>-<b>3</b> were subsequently revealed through computational approaches identifying GSK-3β as a potential target. Docking results indicated that <b>3</b> possessed better binding affinity to GSK-3β, compared with other ligands. All isolated manzamines (<b>1</b>-<b>3</b>) were found to be stable in the binding site. A molecular mechanism is also proposed to provide insights into how manzamines interrupt cancer cells by targeting specifically with GSK-3β.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Host-Symbiont-Pathogen Triad in <i>Bathymodiolus azoricus</i>: The Multifunctional Gill at the Deep-Sea Interface.","authors":"Raul Bettencourt","doi":"10.3390/md24090312","DOIUrl":"10.3390/md24090312","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Deep-sea hydrothermal vents and cold seeps sustain highly productive animal communities through chemosynthetic symbioses, among which bathymodioline mussels are prominent examples. Bathymodioline gill bacteriocytes accommodate intracellular chemosynthetic symbionts, including sulfur- and/or methane-oxidizing bacteria depending on the host species, while remaining sheltered in an epithelium continuously exposed to environmental microorganisms, creating a fundamental immunological problem: how can an innate defense system remain effective without eliminating the microbial partners on which host nutrition depends? This review examines this problem through &lt;i&gt;Bathymodiolus azoricus&lt;/i&gt;, integrating two decades of work on its cellular immunity, gill transcriptome, microbial challenge responses and symbiosis biology with recent mechanistic studies from related bathymodiolines. Central to the present synthesis are previously reported &lt;i&gt;B. azoricus&lt;/i&gt; observations showing that gill tissue can mount local transcriptional responses to bacterial challenge, while hemolymph serum differentially modulates immune-gene expression following exposure to symbiont preparations or non-symbiotic Vibrio. Immune-gene expression also varies along the anterior-posterior gill axis, with lower expression in the posterior budding zone than in mature anterior filaments. We interpret this zonation primarily as a feature of tissue maturation rather than demonstrated active immune suppression, consistent with evidence that newly formed filaments are initially aposymbiotic and become colonized only after formation. Together, these observations evoke a host-symbiont-pathogen triad in which local gill-tissue responses, systemic humoral modulation and gill development constitute interacting levels of immune organization and compartmentalization. As a working hypothesis, we propose that this triad is reconciled principally through spatial and developmental compartmentalization of immune competence rather than through generalized immune suppression, predicting that immune-gene expression should track gill maturation state rather than symbiont occupancy per se. We consider this tissue-level model alongside comparative evidence for putative symbiont-uptake mechanisms, post-engulfment microbial discrimination, lysosomal regulation, symbiont digestion and bacteriocyte turnover, including the mTORC1-dependent phagosome-digestion checkpoint demonstrated in &lt;i&gt;Bathymodiolus japonicus&lt;/i&gt;. Rather than assuming that these mechanisms are conserved across species, we distinguish explicitly between findings established in &lt;i&gt;B. azoricus&lt;/i&gt;, evidence from other bathymodiolines and canonical pathways used as mechanistic context. We conclude by identifying unresolved components of &lt;i&gt;B. azoricus&lt;/i&gt; immunity, including the prophenoloxidase system, the broader antimicrobial-peptide repertoire and the relationship between cellular checkpoints and tissue-level gill zonation, and consider the p","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"αO-Conotoxin GeXIVA[1,2] Attenuates Paclitaxel-Induced Neurotoxicity by Suppressing Ferroptosis via the Nrf2/SLC7A11/GSH/GPX4 Pathway.","authors":"Dongmeng Liu, Jiaqi Yu, Weifeng Xu, Yihong Shen, Xiaoli Feng, Xiaodan Li, Sulan Luo, Jiaolin Bao, Ren-Bo Ding","doi":"10.3390/md24090311","DOIUrl":"10.3390/md24090311","url":null,"abstract":"<p><p>Chemotherapy-induced neurotoxicity, affecting both the central and peripheral nervous systems, is a frequent and severe adverse effect of paclitaxel (PAC) treatment with limited therapeutic options. We previously demonstrated that PAC triggers neuronal cell death via ferroptosis. αO-Conotoxin GeXIVA[1,2], a marine-derived peptide, has shown efficacy in alleviating chemotherapy-induced neuropathic pain. In the present study, we investigated whether GeXIVA[1,2] protects neurons from PAC-induced neurotoxicity by suppressing ferroptosis. Using SH-SY5Y and HT-22 neuronal cell lines, we found that GeXIVA[1,2] pretreatment rescued PAC-impaired cell viability without exhibiting cytotoxicity. GeXIVA[1,2] markedly attenuated PAC-induced reactive oxygen species (ROS) overproduction and restored intracellular glutathione (GSH) levels. Mechanistically, PAC suppressed the Nrf2/SLC7A11/GSH/GPX4 ferroptosis-defense pathway, and GeXIVA[1,2] reactivated this axis by upregulating Nrf2, SLC7A11, and GPX4 protein expression. These results reveal a novel ferroptosis-suppressive function of GeXIVA[1,2] in the context of PAC-induced neurotoxicity. Our findings provide a mechanistic foundation for developing GeXIVA[1,2] as a ferroptosis-targeted intervention against chemotherapy-induced neurotoxicity.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"24 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}