{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:58:38Z","timestamp":1790618318888,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82608237"],"award-info":[{"award-number":["82608237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vascular dementia (VD), a prevalent cognitive disorder mainly resulting from chronic cerebral hypoperfusion\u2010triggered white matter injury (WMI), takes regulation of oligodendrocyte (OL) lineage and restoration of remyelination as key therapeutic targets, whereas the precise role and mechanism of the natural neuroprotective compound emodin in VD\u2010related demyelination have yet to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A VD rat model was generated by bilateral common carotid artery occlusion. After 2\u2009weeks of emodin administration, cognitive function, myelination, and OL lineage were evaluated using behavioral tests, histology, electron microscopy, and immunofluorescence. A comprehensive approach combining proteomics, network pharmacology, molecular docking, dynamics simulations, cellular thermal shift assay (CETSA), and both pharmacological inhibition and activation was applied to systematically elucidate the underlying mechanism of emodin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Emodin administration significantly improved cognitive deficits and reduced WMI in VD rats. It effectively modulated the OL lineage by reducing the elevated proliferative response of OPCs while robustly promoting their maturation and remyelination and inhibiting the RAGE\/ROCK1 signaling pathway in the corpus callosum and hippocampus of VD rats. Mechanistically, CETSA revealed engagement between emodin and RAGE\/ROCK1, and pharmacological inhibition of either RAGE or ROCK1 mimicked the therapeutic benefits of emodin. Conversely, ROCK1 activation reversed emodin\u2010induced improvements in OL maturation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study reveals that emodin modulates the OL lineage to promote remyelination in VD by suppressing the RAGE\/ROCK1 pathway. These results suggest a potential molecular mechanism for emodin and highlight the RAGE\/ROCK1 axis as a therapeutic target for VD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71154","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:41:19Z","timestamp":1789544479000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emodin Suppresses the\n                    <scp>RAGE<\/scp>\n                    \/\n                    <scp>ROCK1<\/scp>\n                    Pathway to Modulate the Oligodendrocyte Lineage and Ameliorate Demyelination in Vascular Dementia Rats"],"prefix":"10.1002","volume":"32","author":[{"given":"Xueqing","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Xin'an Medicine, the Ministry of Education Anhui University of Chinese Medicine  Hefei China"},{"name":"Department of Pharmacy, the First Affiliated Hospital of 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