{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T14:00:34Z","timestamp":1789221634892,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japan Society for the Promotion of Science","award":["19K08850"],"award-info":[{"award-number":["19K08850"]}]},{"name":"the Japan Society for the Promotion of Science","award":["134"],"award-info":[{"award-number":["134"]}]},{"name":"Suzuka University of Medical Science and Konan Chemical Manufacturing Co., Ltd.","award":["19K08850"],"award-info":[{"award-number":["19K08850"]}]},{"name":"Suzuka University of Medical Science and Konan Chemical Manufacturing Co., Ltd.","award":["134"],"award-info":[{"award-number":["134"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Rhamnan sulfate (RS), extracted from the seaweed Monostroma nitidum, suppresses vascular endothelial inflammation and arteriosclerosis, decreases blood glucose levels, and improves blood lipid metabolism and the intestinal environment. We examined whether RS improves hyperglycemia-induced cognitive decline in a hyperglycemic mouse model pretreated with nicotinamide and streptozotocin and then orally administered a high-fat diet and maltodextrin (MD) for 4 months. RS was administered in an MD solution at doses of 75, 225, and 750 mg\/kg of mouse body weight. Administration of RS to hyperglycemic mice significantly reduced blood glucose levels and tended to improve memory function in behavioral pharmacological tests using spontaneous locomotor activity, rotarod test, and eight-way-maze test, although the results were not significant. Brain histopathological analysis showed that RS significantly reduced atrophy of neuronal layers in each region of the hippocampus compared with untreated hyperglycemic controls. RS also significantly suppressed TNF-\u03b1 expression and microglial activation in the brain. These results suggest that RS intake suppresses inflammation in the brain and alleviates the cognitive impairment associated with hyperglycemic diabetes.<\/jats:p>","DOI":"10.3390\/md23060250","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T06:42:48Z","timestamp":1749710568000},"page":"250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rhamnan Sulfate from the Seaweed Monostroma nitidum May Improve Cognitive Impairment Caused by Hyperglycemia"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2715-3496","authenticated-orcid":false,"given":"Takaichi","family":"Miwa","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagakicho 3500-3, Suzuka 513-8670, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2569-4152","authenticated-orcid":false,"given":"Masaya","family":"Sato","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagakicho 3500-3, Suzuka 513-8670, Mie, Japan"},{"name":"Department of Pharmacy, Hinaga General Center for Mental Care, Hinaga 3500, Yokkaichi 510-8575, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7315-8835","authenticated-orcid":false,"given":"Ning","family":"Ma","sequence":"additional","affiliation":[{"name":"Graduate School of Health Science, Suzuka University of Medical Science, Kishioka-cho 1275-3, Suzuka 510-0226, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Hiramoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagakicho 3500-3, Suzuka 513-8670, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-1569","authenticated-orcid":false,"given":"Masahiro","family":"Terasawa","sequence":"additional","affiliation":[{"name":"Konan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagakicho 3500-3, Suzuka 513-8670, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/S1474-4422(11)70188-0","article-title":"Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): A randomized open-label substudy","volume":"10","author":"Launer","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/jdi.12136","article-title":"Trends in the prevalence of type 2 diabetes and prediabetes in community-dwelling Japanese subjects: The Hisayama Study","volume":"5","author":"Mukai","year":"2014","journal-title":"J. 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