{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:42:48Z","timestamp":1783953768039,"version":"3.55.0"},"reference-count":71,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002628","name":"Incheon National University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002628","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Ishige okamurae Yendo (I. okamurae) is a brown macroalga with diverse biological activities. Recently, its ameliorative effects against dementia progression have been demonstrated in various in vitro and in vivo models of Alzheimer\u2019s disease (AD), glutamate excitotoxicity, and bacterial-driven neuroinflammation. I. okamurae extract (IOE) inhibited AD progression by regulating amyloid beta\u2013induced neuronal death and cognitive impairments. Moreover, IOE attenuated glutamate-induced neurodegeneration by modulating the mitogen-activated protein kinases\/Nrf2\/heme oxygenase-1 signaling pathway. Furthermore, IOE effectively suppressed lipopolysaccharide-mediated neuroinflammation and memory deficits by downregulating the Toll-like receptor 4\/MyD88-dependent signaling pathway. Collectively, these findings highlight the potential of IOE as a natural multi-target, anti-dementia agent. In this review, we summarize the neuroprotective and cognition-enhancing properties of IOE, discuss the molecular mechanisms underlying its action, and consider the advantages of I. okamurae as a promising natural resource for effective therapeutic developments that are capable of targeting multiple pathogenic causes of dementia.<\/jats:p>","DOI":"10.3390\/life15111699","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic Potential of Ishige okamurae Yendo as a Multi-Target Inhibitor Against Dementia Symptoms"],"prefix":"10.3390","volume":"15","author":[{"given":"Oh Yun","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Nano-Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 406-772, Republic of Korea"},{"name":"Institute of New-Drug Development, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 406-772, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9941-4195","authenticated-orcid":false,"given":"Seung Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nano-Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 406-772, Republic of Korea"},{"name":"Institute of New-Drug Development, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 406-772, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.amjmed.2018.01.022","article-title":"Dementia","volume":"131","author":"Gale","year":"2018","journal-title":"Am. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: A clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00415-021-10402-2","article-title":"Differentiating dementia with Lewy bodies from Alzheimer\u2019s disease and Parkinson\u2019s disease dementia: An update on imaging modalities","volume":"269","author":"Orad","year":"2022","journal-title":"J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","article-title":"Traumatic Brain Injury and Risk of Neurodegenerative Disorder","volume":"91","author":"Brett","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_6","first-page":"383","article-title":"Malignant Lymphoma of the Brain, and Dementia","volume":"68","author":"Mizutani","year":"2016","journal-title":"Brain Nerve"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/jcbfm.2015.164","article-title":"The neuropathology and cerebrovascular mechanisms of dementia","volume":"36","author":"Raz","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_8","unstructured":"GBD 2019 Dementia Forecasting Collaborators (2022). Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019. Lancet Public Health, 7, e105\u2013e125."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e069780","DOI":"10.1136\/bmj-2021-069780","article-title":"Regulatory decisions diverge over aducanumab for Alzheimer\u2019s disease","volume":"376","author":"Lythgoe","year":"2022","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Malik, R., Kalra, S., Bhatia, S., Harrasi, A.A., Singh, G., Mohan, S., Makeen, H.A., Albratty, M., Meraya, A., and Bahar, B. (2022). Overview of therapeutic targets in management of dementia. Biomed. Pharmacother., 152.","DOI":"10.1016\/j.biopha.2022.113168"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fedele, E. (2023). Anti-Amyloid Therapies for Alzheimer\u2019s Disease and the Amyloid Cascade Hypothesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914499"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: Mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Miculas, D.C., Negru, P.A., Bungau, S.G., Behl, T., Hassan, S.S.U., and Tit, D.M. (2022). Pharmacotherapy Evolution in Alzheimer\u2019s Disease: Current Framework and Relevant Directions. Cells, 12.","DOI":"10.3390\/cells12010131"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1146\/annurev-med-052919-120219","article-title":"Novel Targets for Alzheimer\u2019s Disease: A View Beyond Amyloid","volume":"72","author":"Ray","year":"2021","journal-title":"Annu. Rev. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1113\/JP280875","article-title":"Positive allosteric modulation of NMDA receptors: Mechanisms, physiological impact and therapeutic potential","volume":"600","author":"Geoffroy","year":"2022","journal-title":"J. Physiol."},{"key":"ref_16","first-page":"8253904","article-title":"Acupuncture Attenuates Inflammation in Microglia of Vascular Dementia Rats by Inhibiting miR-93-Mediated TLR4\/MyD88\/NF-\u03baB Signaling Pathway","volume":"2020","author":"Wang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13287-024-03737-w","article-title":"Promoting Alzheimer\u2019s disease research and therapy with stem cell technology","volume":"15","author":"Cao","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Isakovic, J., Serer, K., Barisic, B., and Mitrecic, D. (2023). Mesenchymal stem cell therapy for neurological disorders: The light or the dark side of the force?. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1139359"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.7150\/ijms.21666","article-title":"Ethical and Safety Issues of Stem Cell-Based Therapy","volume":"15","author":"Volarevic","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"El Menyiy, N., El Allam, A., Aboulaghras, S., Jaouadi, I., Bakrim, S., El Omari, N., Shariati, M.A., Miftakhutdinov, A., Wilairatana, P., and Mubarak, M.S. (2022). Inflammatory auto-immune diseases of the intestine and their management by natural bioactive compounds. Biomed. Pharmacother., 151.","DOI":"10.1016\/j.biopha.2022.113158"},{"key":"ref_21","first-page":"420","article-title":"Natural products as reservoirs of novel therapeutic agents","volume":"17","author":"Mushtaq","year":"2018","journal-title":"EXCLI J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7001","DOI":"10.1021\/jf801133h","article-title":"Antioxidant effects of phlorotannins isolated from Ishige okamurae in free radical mediated oxidative systems","volume":"56","author":"Zou","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112221","DOI":"10.1016\/j.foodres.2022.112221","article-title":"Seaweed metabolomics: A review on its nutrients, bioactive compounds and changes in climate change","volume":"163","author":"Park","year":"2023","journal-title":"Food Res. Int."},{"key":"ref_24","first-page":"1921","article-title":"Metabolome profiling of various seaweed species discriminates between brown, red, and green algae","volume":"249","author":"Hamid","year":"2019","journal-title":"Planta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1039\/c3np70057g","article-title":"Biogeography and biodiscovery hotspots of macroalgal marine natural products","volume":"30","author":"Leal","year":"2013","journal-title":"Nat. Prod. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kim, M., Cho, C., Lee, C., Ryu, B., Kim, S., Hur, J., and Lee, S.H. (2021). Ishige okamurae Ameliorates Methylglyoxal-Induced Nephrotoxicity via Reducing Oxidative Stress, RAGE Protein Expression, and Modulating MAPK, Nrf2\/ARE Signaling Pathway in Mouse Glomerular Mesangial Cells. Foods, 10.","DOI":"10.3390\/foods10092000"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/ptr.2674","article-title":"Anti-inflammatory effect of Ishige okamurae ethanolic extract via inhibition of NF-\u03baB transcription factor in RAW 264.7 cells","volume":"23","author":"Kim","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.diabres.2011.03.018","article-title":"Ishige okamurae ameliorates hyperglycemia and insulin resistance in C57BL\/KsJ-db\/db mice","volume":"93","author":"Min","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1901220","DOI":"10.1002\/mnfr.201901220","article-title":"Ameliorating Activity of Ishige okamurae on the Amyloid Beta-Induced Cognitive Deficits and Neurotoxicity through Regulating ERK, p38 MAPK, and JNK Signaling in Alzheimer\u2019s Disease-Like Mice Model","volume":"64","author":"Kwon","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kwon, O.Y., and Lee, S.H. (2021). Ishige okamurae Suppresses Trimethyltin-Induced Neurodegeneration and Glutamate-Mediated Excitotoxicity by Regulating MAPKs\/Nrf2\/HO-1 Antioxidant Pathways. Antioxidants, 10.","DOI":"10.3390\/antiox10030440"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kwon, O.Y., and Lee, S.H. (2022). Ishige okamurae Attenuates Neuroinflammation and Cognitive Deficits in Mice Intracerebroventricularly Injected with LPS via Regulating TLR-4\/MyD88-Dependent Pathways. Antioxidants, 12.","DOI":"10.3390\/antiox12010078"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer\u2019s Disease: Causes and Treatment. Molecules, 25.","DOI":"10.3390\/molecules25245789"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid beta-based therapy for Alzheimer\u2019s disease: Challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Araki, W. (2023). Abeta Oligomer Toxicity-Reducing Therapy for the Prevention of Alzheimer\u2019s Disease: Importance of the Nrf2 and PPARgamma Pathways. Cells, 12.","DOI":"10.3390\/cells12101386"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic Abeta oligomer and Alzheimer\u2019s disease: An emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1002\/jcb.30141","article-title":"Distinct types of amyloid-beta oligomers displaying diverse neurotoxicity mechanisms in Alzheimer\u2019s disease","volume":"122","author":"Madhu","year":"2021","journal-title":"J. Cell. Biochem."},{"key":"ref_37","first-page":"802","article-title":"Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease\/Metabolic Dysfunction-associated Steatotic Liver Disease","volume":"12","author":"Hu","year":"2024","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1126\/science.adk0830","article-title":"Side effects loom over Alzheimer\u2019s drugs","volume":"381","year":"2023","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neuropharm.2013.04.014","article-title":"NMDA receptors and memory encoding","volume":"74","author":"Morris","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S191","DOI":"10.33549\/physiolres.932678","article-title":"Structure, function, and pharmacology of NMDA receptor channels","volume":"63","author":"Vyklicky","year":"2014","journal-title":"Physiol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40035-021-00278-7","article-title":"Excitotoxicity, calcium and mitochondria: A triad in synaptic neurodegeneration","volume":"11","author":"Verma","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jphs.2020.07.011","article-title":"Glutamate-induced excitotoxicity in Parkinson\u2019s disease: The role of glial cells","volume":"144","author":"Iovino","year":"2020","journal-title":"J. Pharmacol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3233\/JAD-160763","article-title":"Role of Glutamate and NMDA Receptors in Alzheimer\u2019s Disease","volume":"57","author":"Wang","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.neurobiolaging.2014.09.006","article-title":"Abeta and NMDAR activation cause mitochondrial dysfunction involving ER calcium release","volume":"36","author":"Ferreira","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pardo-Moreno, T., Gonzalez-Acedo, A., Rivas-Dominguez, A., Garcia-Morales, V., Garcia-Cozar, F.J., Ramos-Rodriguez, J.J., and Melguizo-Rodriguez, L. (2022). Therapeutic Approach to Alzheimer\u2019s Disease: Current Treatments and New Perspectives. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061117"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41580-022-00456-z","article-title":"Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology","volume":"23","author":"Sies","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Choi, Y.K., and Kim, Y.M. (2022). Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137041"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/jnc.13607","article-title":"Neuroinflammation: The devil is in the details","volume":"139","author":"DiSabato","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12974-021-02071-9","article-title":"Activated STAT3 signaling pathway by ligature-induced periodontitis could contribute to neuroinflammation and cognitive impairment in rats","volume":"18","author":"Hu","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Qin, Z., Zhou, C., Xiao, X., and Guo, C. (2021). Metformin attenuates sepsis-induced neuronal injury and cognitive impairment. BMC Neurosci., 22.","DOI":"10.1186\/s12868-021-00683-8"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tran, V.T.A., Lee, L.P., and Cho, H. (2022). Neuroinflammation in neurodegeneration via microbial infections. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.907804"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Emery, D.C., Shoemark, D.K., Batstone, T.E., Waterfall, C.M., Coghill, J.A., Cerajewska, T.L., Davies, M., West, N.X., and Allen, S.J. (2017). 16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer\u2019s Post-Mortem Brain. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00195"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Fulop, T., Witkowski, J.M., Bourgade, K., Khalil, A., Zerif, E., Larbi, A., Hirokawa, K., Pawelec, G., Bocti, C., and Lacombe, G. (2018). Can an Infection Hypothesis Explain the Beta Amyloid Hypothesis of Alzheimer\u2019s Disease?. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00224"},{"key":"ref_55","first-page":"1108","article-title":"Microbiota-Gut-Brain Axis Dysregulation in Alzheimer\u2019s Disease: Multi-Pathway Effects and Therapeutic Potential","volume":"15","author":"Qu","year":"2024","journal-title":"Aging Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12974-019-1564-7","article-title":"The endotoxin hypothesis of neurodegeneration","volume":"16","author":"Brown","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/glia.21094","article-title":"Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NF\u03baB signaling, MAPK, and Jak1\/Stat1 pathways","volume":"59","author":"Gorina","year":"2011","journal-title":"Glia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Malko, P., Syed Mortadza, S.A., McWilliam, J., and Jiang, L.H. (2019). TRPM2 Channel in Microglia as a New Player in Neuroinflammation Associated With a Spectrum of Central Nervous System Pathologies. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00239"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/s41401-021-00702-8","article-title":"Luteolin alleviates cognitive impairment in Alzheimer\u2019s disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation","volume":"43","author":"Kou","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Stojanovic, T.D., Rakic, M.R., Cosic, M.V., Oalde Pavlovic, M.M., Sabovljevic, A.D., Sabovljevic, M.S., Bozic, B.D., Bozic Nedeljkovic, B.D., Vujicic, M.M., and Lunic, T.M. (2025). Moss Extracts as Natural Neuroprotective Agents: Mitigating LPS-Induced Neuroinflammation and Microglial Activation. Cells, 14.","DOI":"10.3390\/cells14110780"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12016-013-8402-y","article-title":"TLR2 and TLR4 in autoimmune diseases: A comprehensive review","volume":"47","author":"Liu","year":"2014","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Cui, W., Sun, C., Ma, Y., Wang, S., Wang, X., and Zhang, Y. (2020). Inhibition of TLR4 Induces M2 Microglial Polarization and Provides Neuroprotection via the NLRP3 Inflammasome in Alzheimer\u2019s Disease. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00444"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Chen, Y., Xu, C., Zhang, H., and Lin, C. (2020). TLR4 Targeting as a Promising Therapeutic Strategy for Alzheimer Disease Treatment. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.602508"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lee, H.L., Go, M.J., Lee, H.S., and Heo, H.J. (2024). Ecklonia cava Ameliorates Cognitive Impairment on Amyloid beta-Induced Neurotoxicity by Modulating Oxidative Stress and Synaptic Function in Institute of Cancer Research (ICR) Mice. Antioxidants, 13.","DOI":"10.3390\/antiox13080951"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"359","DOI":"10.4014\/jmb.1910.10068","article-title":"Neuroprotective Effects of Phlorotannin-Rich Extract from Brown Seaweed Ecklonia cava on Neuronal PC-12 and SH-SY5Y Cells with Oxidative Stress","volume":"30","author":"Nho","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Jo, S.L., Yang, H., Jeong, K.J., Lee, H.W., and Hong, E.J. (2023). Neuroprotective Effects of Ecklonia cava in a Chronic Neuroinflammatory Disease Model. Nutrients, 15.","DOI":"10.3390\/nu15082007"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bogie, J., Hoeks, C., Schepers, M., Tiane, A., Cuypers, A., Leijten, F., Chintapakorn, Y., Suttiyut, T., Pornpakakul, S., and Struik, D. (2019). Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer\u2019s disease mouse model. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-41399-4"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ko, W., Lee, H., Kim, N., Jo, H.G., Woo, E.R., Lee, K., Han, Y.S., Park, S.R., Ahn, G., and Cheong, S.H. (2021). The Anti-Oxidative and Anti-Neuroinflammatory Effects of Sargassum horneri by Heme Oxygenase-1 Induction in BV2 and HT22 Cells. Antioxidants, 10.","DOI":"10.3390\/antiox10060859"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5416","DOI":"10.3390\/cimb44110367","article-title":"Sargassum horneri (Turner) C. Agardh Extract Regulates Neuroinflammation In Vitro and In Vivo","volume":"44","author":"Cho","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1007\/s12010-012-9545-7","article-title":"Neuroprotective effect of phlorotannin isolated from Ishige okamurae against H2O2-induced oxidative stress in murine hippocampal neuronal cells, HT22","volume":"166","author":"Heo","year":"2012","journal-title":"Appl. Biochem. Biotechnol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T05:36:26Z","timestamp":1762234586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":71,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["life15111699"],"URL":"https:\/\/doi.org\/10.3390\/life15111699","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,1]]}}}