{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:18Z","timestamp":1785412518082,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["FWFE-2024-0007"],"award-info":[{"award-number":["FWFE-2024-0007"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FWFE-2024-0007"],"award-info":[{"award-number":["FWFE-2024-0007"]}],"id":[{"id":"https:\/\/ror.org\/00ghqgy32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Ether phospholipids from marine organisms represent an understudied class of bioactive lipids with unique structural features. In this study, we isolated, for the first time, an ether phosphatidylserine (ePS) species from the soft coral Sclerophytum heterospiculatum and assessed its biological activity on human microglial clone 3 (HMC-3) cells. The isolated ePS contained an ether bond at the sn-1 position and very-long-chain polyunsaturated fatty acids (PUFA) (24:5) at the sn-2 position. Using an MTS assay, we demonstrated that ePS was non-cytotoxic at all tested concentrations (0.39\u2013100 \u03bcg\/mL) and even increased microglial proliferation at 50\u2013100 \u03bcg\/mL. In microglial cells activated by lipopolysaccharide (LPS-activated), ePS significantly reduced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). A lipidomic analysis by HPLC\u2013MS\/MS revealed that ePS modulated the membrane lipid composition of microglial cells, increasing the content of polyunsaturated phosphatidylserines (PS 36:3, PS 40:5) and decreasing the levels of phosphatidylinositols (PI 18:1\/20:4; PI 18:0\/20:4, 18:1\/20:3). Furthermore, a fatty acid analysis showed that ePS prevented LPS-induced accumulation of saturated fatty acids and preserved PUFA levels in HMC-3 cells. These findings suggest that marine-derived ePS can be considered as promising agents with antioxidant and anti-inflammatory properties.<\/jats:p>","DOI":"10.3390\/md24060188","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:30:33Z","timestamp":1779669033000},"page":"188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ether Phosphatidylserine from Soft Coral Sclerophytum heterospiculatum Reveals Antioxidant Activity and Modulates Lipid Composition in LPS-Activated Human Microglial HMC-3 Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7707-1602","authenticated-orcid":false,"given":"Elena T.","family":"Bizikashvili","sequence":"first","affiliation":[{"name":"A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, ul. Palchevskogo 17, 690041 Vladivostok, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9830-1669","authenticated-orcid":false,"given":"Arina I.","family":"Ponomarenko","sequence":"additional","affiliation":[{"name":"A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, ul. Palchevskogo 17, 690041 Vladivostok, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina V.","family":"Ermolenko","sequence":"additional","affiliation":[{"name":"A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, ul. Palchevskogo 17, 690041 Vladivostok, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor V.","family":"Manzhulo","sequence":"additional","affiliation":[{"name":"A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, ul. Palchevskogo 17, 690041 Vladivostok, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref_1","unstructured":"Fabricius, K., and Alderslade, P. (2001). Soft Corals and Sea Fans: A Comprehensive Guide to the Tropical Shallow Water Genera of the Central-West Pacific, the Indian Ocean and the Red Sea."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104167","DOI":"10.1016\/j.bioorg.2020.104167","article-title":"Uncommon terpenoids with anti-inflammatory activity from the Hainan soft coral Sinularia tumulosa","volume":"104","author":"Cai","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.3390\/md11124741","article-title":"New sinularianin sesquiterpenes from soft coral Sinularia sp.","volume":"11","author":"Yang","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1007\/s12272-016-0759-z","article-title":"Endoperoxy and hydroperoxy cadinane-type sesquiterpenoids from an Okinawan soft coral, Sinularia sp.","volume":"39","author":"Roy","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1080\/14786419.2017.1402326","article-title":"Eudesmane and aromadendrane sesquiterpenoids from the vietnamese soft coral Sinularia erecta","volume":"32","author":"Huong","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Qin, G.-F., Tang, X.-L., Sun, Y.-T., Luo, X.-C., Zhang, J., Van Ofwegen, L., Sung, P.-J., Li, P.-L., and Li, G.-Q. (2018). Terpenoids from the soft coral Sinularia sp. collected in Yongxing island. Mar. Drugs, 16.","DOI":"10.3390\/md16040127"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chu, M.-J., Tang, X.-L., Han, X., Li, T., Luo, X.-C., Jiang, M.-M., Van Ofwegen, L., Luo, L.-Z., Zhang, G., and Li, P.-L. (2018). Metabolites from the Paracel islands soft coral Sinularia cf. molesta. Mar. Drugs, 16.","DOI":"10.3390\/md16120517"},{"key":"ref_8","first-page":"1000205","article-title":"Distribution of very-long-chain fatty acids between molecular species of different phospholipid classes of two soft corals","volume":"4","author":"Imbs","year":"2015","journal-title":"Biochem. Anal. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1134\/S1068162019010151","article-title":"Study of total lipidome of the Sinularia siaesensis soft coral","volume":"44","author":"Sikorskaya","year":"2018","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s13238-017-0423-5","article-title":"Structural and functional roles of ether lipids","volume":"9","author":"Dean","year":"2018","journal-title":"Protein Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105422","DOI":"10.1016\/j.chemphyslip.2024.105422","article-title":"Phosphatidylserine: A comprehensive overview of synthesis, metabolism, and nutrition","volume":"264","author":"Hussain","year":"2024","journal-title":"Chem. Phys. Lipids"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plipres.2014.06.002","article-title":"Phosphatidylserine in the brain: Metabolism and function","volume":"56","author":"Kim","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/10236244.2022.2120816","article-title":"Recovery of a symbiotic octocoral Sinularia heterospiculata after heat stress exposure","volume":"55","author":"Sikorskaya","year":"2022","journal-title":"Mar. Freshw. Behav. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s12974-018-1288-0","article-title":"The human microglial HMC3 cell line: Where do we stand? A systematic literature review","volume":"15","author":"Cappoli","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nri.2017.125","article-title":"Microglia and macrophages in brain homeostasis and disease","volume":"18","author":"Li","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Caruso, G., Benatti, C., Blom, J.M.C., Caraci, F., and Tascedda, F. (2019). The many faces of mitochondrial dysfunction in depression: From pathology to treatment. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00995"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1124\/jpet.116.237503","article-title":"Oxidative stress and the central nervous system","volume":"360","author":"Salim","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s11154-019-09512-0","article-title":"Dietary lipids, gut microbiota and lipid metabolism","volume":"20","author":"Schoeler","year":"2019","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100048","DOI":"10.1016\/j.cpnec.2021.100048","article-title":"LPS and palmitic acid co-upregulate microglia activation and neuroinflammatory response","volume":"6","author":"Lu","year":"2021","journal-title":"Compr. Psychoneuroendocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12407","DOI":"10.1074\/jbc.M110.191783","article-title":"Direct activation of human phospholipase C by its well known inhibitor U73122","volume":"286","author":"Klein","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s12017-009-8092-z","article-title":"Phospholipases A2 and inflammatory responses in the central nervous system","volume":"12","author":"Sun","year":"2010","journal-title":"Neuromol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.plefa.2017.01.012","article-title":"Dynamic interactions of n-3 and n-6 fatty acid nutrients","volume":"136","author":"Lands","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gil-de-G\u00f3mez, L., Astudillo, A.M., Lebrero, P., Balboa, M.A., and Balsinde, J. (2017). Essential role for ethanolamine plasmalogen hydrolysis in bacterial lipopolysaccharide priming of macrophages for enhanced arachidonic acid release. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01251"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1007\/s00343-021-1141-7","article-title":"Cytological and transcriptional analysis reveal phosphatidylinositol signaling pathway plays key role in mitotic division of Pyropia yezoensis","volume":"40","author":"Zhu","year":"2022","journal-title":"J. Ocean. Limnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s11010-011-1023-y","article-title":"Phosphatidylinositol 3-kinase inhibitor suppresses inducible nitric oxide synthase expression in bronchiole epithelial cells in asthmatic rats","volume":"359","author":"Xia","year":"2012","journal-title":"Mol. Cell Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.bbadis.2012.05.008","article-title":"Functions of plasmalogen lipids in health and disease","volume":"1822","author":"Braverman","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.chemphyslip.2011.04.010","article-title":"Ether lipids","volume":"164","author":"Magnusson","year":"2011","journal-title":"Chem. Phys. Lipids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1016\/j.biocel.2013.06.004","article-title":"Ceramide metabolism in mouse tissue","volume":"45","author":"Schiffmann","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_30","unstructured":"Rouser, G., Kritchevsky, G., and Yamamoto, A. (1967). Column chromatographic and associated procedures for separation and determination of phosphatides and glycolipids. Lipid Chromatographic Analysis, Marcel Dekker."},{"key":"ref_31","unstructured":"Markossian, S., Grossman, A., Baskir, H., Arkin, M., Auld, D., Austin, C., Baell, J., Brimacombe, K., Chung, T.D.Y., and Coussens, N.P. (2004). Cell Viability Assays, Assay Guidance Manual."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1021\/acs.analchem.7b00043","article-title":"Preparation and practical applications of 2\u2032,7\u2032-dichlorodihydrofluorescein in redox assays","volume":"89","author":"Reiniers","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1878","DOI":"10.21769\/BioProtoc.1878","article-title":"Fluorescent detection of intracellular nitric oxide in Staphylococcus aureus","volume":"6","author":"Lewis","year":"2016","journal-title":"Bio-protocol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/S0021-9673(00)88356-9","article-title":"Adaptation of a macro-scale method to the micro-scale for fatty acid methyl transesterification of biological lipid extracts","volume":"151","author":"Carreau","year":"1978","journal-title":"J. Chromatogr. A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1134\/S106816202202008X","article-title":"Distribution of fatty acids in storage and structural lipids of the holothurian Eupentacta fraudatrix","volume":"48","author":"Ermolenko","year":"2022","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/jhrc.1240200305","article-title":"Standard equivalent chain length values of monoenic and polyenic (methylene interrupted) fatty acids","volume":"20","year":"1997","journal-title":"J. High Resol. Chromatogr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s11745-015-4021-0","article-title":"Fatty acid, lipid class, and phospholipid molecular species composition of the soft coral Xenia sp. (Nha Trang Bay, the South China Sea, Vietnam)","volume":"50","author":"Imbs","year":"2015","journal-title":"Lipids"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Imbs, A.B., Dang, L.P.T., and Nguyen, K.B. (2019). Comparative lipidomic analysis of phospholipids of hydrocorals and corals from tropical and cold-water regions. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215759"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/6\/188\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:13:43Z","timestamp":1779682423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/6\/188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,23]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["md24060188"],"URL":"https:\/\/doi.org\/10.3390\/md24060188","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,23]]}}}