{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:04:57Z","timestamp":1787803497052,"version":"build-2784847793"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Pearl and nacre have been used in traditional medicines for treating brain dysfunctions, such as epilepsy, myopia, palpitations and convulsions. We previously showed that a pearl oyster nacre extract improves scopolamine-induced memory impairments using the Y-maze, Banes maze and object recognition tests. In this study, we aimed to isolate the memory-improving substance using ion-exchange column chromatography and reverse-phase column chromatography and elucidate the molecular mechanism underlying its memory-improving activity. The isolated substance was found to be a sulfated polysaccharide with a molecular weight of approximately 750 kDa. Monosaccharide composition analysis showed that it was rich in galactose, glucose, mannose and uronic acid. Furthermore, the mRNA expression levels of oxidative stress, inflammatory response and neuroprotective factors in the cerebral cortex were investigated. Treatment with the polysaccharide increased the expression levels of the antioxidant enzymes Cu, Zn -superoxide dismutase (SOD) and catalase and attenuated the scopolamine-mediated upregulation of the inflammatory cytokines interleukin-1 and interleukin-6. In addition, the polysaccharide suppressed the decrease in the expression levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These findings strongly suggest that the polysaccharide in the nacre extract mediated its antiamnesic effects by preventing oxidative stress and inflammation and increasing the expression levels of BDNF and NGF.<\/jats:p>","DOI":"10.3390\/antiox10040505","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T15:42:19Z","timestamp":1616600539000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Sulfated Polysaccharide Isolated from the Nacre of Pearl Oyster Improves Scopolamine-Induced Memory Impairment"],"prefix":"10.3390","volume":"10","author":[{"given":"Hikaru","family":"Yamagami","sequence":"first","affiliation":[{"name":"College of Environmental Technology, Muroran Institute of Technology, 27-1 Mizumoto, Muroran 050-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Fuji","sequence":"additional","affiliation":[{"name":"College of Environmental Technology, Muroran Institute of Technology, 27-1 Mizumoto, Muroran 050-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Wako","sequence":"additional","affiliation":[{"name":"College of Environmental Technology, Muroran Institute of Technology, 27-1 Mizumoto, Muroran 050-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-721X","authenticated-orcid":false,"given":"Yasushi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"College of Environmental Technology, Muroran Institute of Technology, 27-1 Mizumoto, Muroran 050-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kinoshita, S., Wang, N., Inoue, H., Maeyama, K., Okamoto, K., Nagai, K., Kondo, H., Hirono, I., Asakawa, S., and Watabe, S. (2011). Deep sequencing of ESTs from nacreous and prismatic layer producing tissues and a screen for novel shell formation- related genes in the pearl oyster. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021238"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jep.2016.01.039","article-title":"Anticonvulsant and sedative\u2013hypnotic activity screening of pearl and nacre (mother of pearl)","volume":"181","author":"Zhang","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/phrs.2000.0780","article-title":"A study on the prevention and treatment of myopia with nacre on chicks","volume":"44","author":"Xu","year":"2001","journal-title":"Pharmacol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S0002-9343(02)01353-0","article-title":"What is the role of the clinical \u201cpearl\u201d?","volume":"113","author":"Mangrulkar","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/raq.12225","article-title":"Shells from aquaculture: A valuable biomaterial, not a nuisance waste product","volume":"11","author":"Morris","year":"2019","journal-title":"Aquaculture"},{"key":"ref_6","first-page":"1","article-title":"The water-soluble matrix fraction from the nacre of Pinctada maxima produces earlier mineralization of MC3T3-E1 mouse pre-osteoblasts","volume":"135","author":"Rousseau","year":"2003","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.jsb.2015.10.012","article-title":"Nacre extract restores the mineralization capacity of subchondral osteoarthritis osteoblasts","volume":"192","author":"Brion","year":"2015","journal-title":"J. Struct. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/S0142-9612(98)90212-5","article-title":"Interface between bone and nacre implants in sheep","volume":"20","author":"Atlan","year":"1999","journal-title":"Biomaterials"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/31798","article-title":"A marriage of bone and nacre","volume":"392","author":"Westbroek","year":"1998","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0764-4469(97)86933-8","article-title":"Reconstruction of human maxillary defects with nacre powder: Histological evidence for bone regeneration","volume":"320","author":"Atlan","year":"1997","journal-title":"C. R. Acad. Sci. III"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/1097-4636(200111)57:2<306::AID-JBM1172>3.0.CO;2-H","article-title":"Comparative effects of nacre water-soluble matrix and dexamethasone on the alkaline phosphatase activity of MRC-5 fibroblasts","volume":"57","author":"Almeida","year":"2001","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chaturvedi, R., Singha, P.K., and Dey, S. (2013). Water Soluble Bioactives of Nacre Mediate Antioxidant Activity and Osteoblast Differentiation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0084584"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1007\/s10126-006-6037-1","article-title":"A novel matrix protein p10 from the nacre of pearl oyster (Pinctada fucata) and its effects on both CaCO3 crystal formation and mineralogenic cells","volume":"8","author":"Zhang","year":"2006","journal-title":"Mar. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cbpb.2007.05.010","article-title":"Characterization and in vitro mineralization function of a soluble protein complex P60 from the nacre of Pinctada fucata","volume":"148","author":"Lao","year":"2007","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.cbpb.2010.11.004","article-title":"Pinctada fucata mantle gene 3 (PFMG3) promotes differentiation in mouseo steoblasts (MC3T3-E1)","volume":"158","author":"Wang","year":"2011","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1007\/s11033-011-1088-4","article-title":"Nacre-driven water-soluble factors promote wound healing of the deep burn porcine skin by recovering angiogenesis and fibroblast function","volume":"39","author":"Lee","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1054\/tice.1999.0091","article-title":"Stimulation of rat cutaneous fibroblasts and their synthetic activity by implants of powdered nacre (mother of pearl)","volume":"32","author":"Lopez","year":"2000","journal-title":"Tissue Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1080\/03639045.2019.1593436","article-title":"Nanoscaled pearl powder accelerates wound repair and regeneration in vitro and in vivo","volume":"45","author":"Chen","year":"2019","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jfda.2017.05.010","article-title":"Efficacy of protein rich pearl powder on antioxidant status in a randomized placebo-controlled trial","volume":"26","author":"Chiu","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.4103\/1995-7645.228434","article-title":"Nacre extract prevents scopolamine-induced memory deficits in rodents","volume":"11","author":"Fuji","year":"2018","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.apjtm.2016.05.019","article-title":"Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity","volume":"9","author":"Hasegawa","year":"2016","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.ijbiomac.2020.11.004","article-title":"Increased antioxidant activity and improved structural characterization of sulfuric acid-treated stepwise degraded polysaccharides from Pholiota nameko PN-01","volume":"166","author":"Zheng","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ijbiomac.2020.01.072","article-title":"Native \u03ba-carrageenan induced-colitis is related to host intestinal microecology","volume":"147","author":"Mi","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1002\/fsn3.1608","article-title":"Scallop mantle toxin induces apoptosis in liver tissues of mice","volume":"8","author":"Kariya","year":"2020","journal-title":"Food Sci. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assem-bly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/abio.1996.0292","article-title":"The ferric reducing ability of plasma (FRAP) as a measure of \u201cantioxidant power\u201d: The FRAP assay","volume":"239","author":"Benzie","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.foodhyd.2011.02.009","article-title":"FTIR-ATR spectroscopy as a tool for polysaccharide identification in edible brown and red seaweeds","volume":"25","year":"2011","journal-title":"Food Hydrocoll."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0308-8146(99)00191-0","article-title":"Determination of pectin degree of esterification by diffuse reflectance Fourier transform infrared spectroscopy","volume":"68","author":"Gnanasambandam","year":"2000","journal-title":"Food Chem."},{"key":"ref_29","first-page":"163","article-title":"Study on the preparation of hydroxy ethylchitosan sulfate","volume":"19","author":"Fang","year":"1998","journal-title":"Chin. J. Biochem. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.carbpol.2017.05.014","article-title":"Structural characterization and immunomodulatory activity of awater soluble polysaccharide isolated from Botrychium ternatum","volume":"171","author":"Zhao","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pannakal, S.T., Ja\u00c8ger, S., Duranton, A., Tewari, A., Saha, S., Radhakrishnan, A., Roy, N., Kuntz, J.F., Fermas, S., and James, D. (2017). Longevity effect of a polysaccharide from Chlorophytum borivilianum on Caenorhabditis elegans and Saccharomyces cerevisiae. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179813"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1039\/C9AN02440A","article-title":"Rapid quality control of medicine and food dual purpose plant polysaccharides by matrix assisted laser desorption\/ionization mass spectrometry","volume":"145","author":"Wang","year":"2020","journal-title":"Analyst"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1021\/cg901389v","article-title":"Matrix interactions in biomineralization: Aragonite nucleation by an intrinsically disordered nacre polypeptide, n16N, associated with a \u03b2-chitin substrate","volume":"10","author":"Keene","year":"2010","journal-title":"Cryst. Growth Des."},{"key":"ref_34","first-page":"6","article-title":"The soluble matrix of Mercenaria mercenaria shell","volume":"6","author":"Crenshaw","year":"1972","journal-title":"Biominer. Res. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/jez.1402370104","article-title":"Mollusk shell organic matrix: Fourier transform infrared study of the acidic macromolecules","volume":"237","author":"Worms","year":"1986","journal-title":"J. Exp. Zool."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ijbiomac.2019.09.243","article-title":"The degraded polysaccharide from Pyropia haitanensis represses amyloid beta peptide-induced neurotoxicity and memory in vivo","volume":"146","author":"Zhang","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1535370219894558","article-title":"Angelica polysaccharide ameliorates memory impairment in Alzheimer\u2019s disease rat through activating BDNF\/TrkB\/CREB pathway","volume":"245","author":"Du","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"37127","DOI":"10.1039\/C9RA08245J","article-title":"(Grifola frondosa) polysaccharide ameliorates Alzheimer\u2019s disease-like pathology and cognitive impairments by enhancing microglial amyloid-b clearance","volume":"9","author":"Bai","year":"2019","journal-title":"RSC Adv."},{"key":"ref_39","first-page":"1","article-title":"Attenuation of scopolamine-Induced Learning and Memory Impairment by Ceriporia lacerata Mycelial Culture in C57BL\/6 Mouse Model","volume":"34","author":"Lee","year":"2020","journal-title":"FASEB J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18242","DOI":"10.1074\/jbc.RA117.001245","article-title":"Mini-GAGR, an intranasally applied polysaccharide, activates the neuronal Nrf2-mediated antioxidant defense system","volume":"293","author":"Murphy","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhu, L., Li, R., Jiao, S., Wei, J., Yan, Y., Wang, Z.A., Li, J., and Du, Y. (2020). Blood-brain Barrier Permeable chitosan Oligosaccharides Interfere with \u03b2-amyloid Aggregation and Alleviate \u03b2-amyloid Protein Mediated Neurotoxicity and Neuroinflammation in a Dose- and Degree of PolymerizationDependent Manner. Mar. Drugs, 18.","DOI":"10.3390\/md18100488"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Biase, E.D., Lunghi, G., Maggioni, M., Fazzari, M., Pom\u00e8, D.Y., Loberto, N., Ciampa, M.G., Fato, P., Mauri, L., and Sevin, E. (2020). GM1 oligosaccharide crosses the human blood-brain Barrier in vitro by a paracellular route. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082858"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/ptr.6804","article-title":"Protective effect of ginsenoside Rh2 on scopolamine-induced memory deficits through regulation of cholinergic transmission, oxidative stress and the ERK-CREB-BDNF signaling pathway","volume":"35","author":"Lv","year":"2020","journal-title":"Phytoter. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1055\/a-1018-5402","article-title":"Lespedeza bicolor extract improves amyloid beta25-35-induced memory impairments by upregulating BDNF and activating Akt, ERK, an CREB signaling in mice","volume":"85","author":"Ko","year":"2019","journal-title":"Planta Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jff.2017.10.014","article-title":"Phlorotannin-rich fraction from Ishige foliacea brown seaweed prevents the scopolamine-induced memory impairment via regulation of ERK-CREB BDNF pathway","volume":"40","author":"Um","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0896-6273(00)81010-7","article-title":"Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism","volume":"20","author":"Tao","year":"1998","journal-title":"Neuron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17681","DOI":"10.1074\/jbc.M600207200","article-title":"CAAT\/Enhancer-binding Protein and cAMP-response Element-binding Protein Mediate Inducible Expression of the Nerve Growth Factor Gene in the central nervous system","volume":"281","author":"McCauslin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13089","DOI":"10.1523\/JNEUROSCI.0457-10.2010","article-title":"Transgenic mice with chronic NGF deprivation and Alzheimer\u2019s disease-like pathology display hippocampal region-specific impairments in short- and long-term plasticities","volume":"30","author":"Houeland","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107125","DOI":"10.1016\/j.nlm.2019.107125","article-title":"BDNF induces in vivo long-lasting enhancement of synaptic transmission and structural reorganization at the hippocampal mossy fibers in a transcription and translation-independent manner","volume":"167","author":"Escobar","year":"2020","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s10571-017-0510-4","article-title":"BDNF: A key factor with multipotent impact on brain signaling and synaptic plasticity","volume":"38","author":"Lietzau","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lee, J.S., Hong, S.S., Kim, H.G., Lee, H.W., Kim, W.Y., Lee, S.K., and Son, C.G. (2016). Gongjin-Dan enhances hippocampal memory in a mouse model of scopolamine-induced amnesia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159823"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.biopha.2018.12.100","article-title":"CGY-1, a biflavonoid isolated from Cardiocrinum giganteum seeds, improves memory deficits by modulating the cholinergic system in scopolamine treated mice","volume":"111","author":"Zhang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","first-page":"1","article-title":"Ethyl acetate Extract Components Bushen-Yizhi Formula Provides Neuroprotection against scopolamine-induced Cognitive Impairment","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5","DOI":"10.29252\/nirp.bcn.9.1.5","article-title":"Comparison of memory impairment and oxidative stress following single or repeated doses administration of scopolamine in rat hippocampus","volume":"9","author":"Rahimzadegan","year":"2018","journal-title":"Basic Clin. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1007\/s11481-018-9824-3","article-title":"Melatonin rescue oxidative stress-mediated neuroinflammation\/ neurodegeneration and memory impairment in scopolamine-induced amnesia mice model","volume":"14","author":"Muhammad","year":"2019","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Iqbal, S., Shah, F.A., Naeem, K., Nadeem, H., Sarwar, S., Ashraf, Z., Imran, M., Khan, T., Anwar, T., and Li, S. (2020). Succinamide derivatives ameliorate neuroinflammation and oxidative stress in scopolamine-induced neurodegeneration. 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