{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:08:00Z","timestamp":1778854080371,"version":"3.51.4"},"reference-count":43,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271228"],"award-info":[{"award-number":["82271228"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>Diabetic encephalopathy (DE) is a severe complication of the central nervous system associated with diabetes. In this study, we investigated the regulatory role of mammalian target of rapamycin (mTOR) on nuclear factor \u03baB (NF-\u03baB) in mice with DE, and the neuroprotective effect and therapeutic mechanisms of luteolin, a natural flavonoid compound with anti-inflammatory, antioxidant, and neuroprotective properties. The results indicated that treatment with luteolin improved the degree of cognitive impairment in mice with DE. It also decreased the levels of phosphorylated mTOR, phosphorylated NF-\u03baB, and histone deacetylase 2 (HDAC2) and increased the expression of brain-derived neurotrophic factor and synaptic-related proteins. Furthermore, protein-protein interaction and the Gene Ontology analysis revealed that luteolin was involved in the regulatory network of HDAC2 expression through the mTOR\/NF-\u03baB signaling cascade. Our bioinformatics and molecular docking results indicated that luteolin may also directly target HDAC2, as an HDAC2 inhibitor, to alleviate DE, complementing mTOR\/NF-\u03baB signaling inhibition. Analysis of luteolin\u2019s target proteins and their interactions suggest an effect on HDAC2 and cognition. In conclusion, HDAC2 and tau hyperphosphorylation are regulated by the mTOR\/NF-\u03baB signaling cascade in DE, and luteolin is found to reverse these effects, demonstrating its protective role in DE.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.2337\/db23-0969","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T13:40:48Z","timestamp":1718286048000},"page":"1513-1526","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["Regulatory Role of NF-\u03baB on HDAC2 and Tau Hyperphosphorylation in Diabetic Encephalopathy and the Therapeutic Potential of Luteolin"],"prefix":"10.2337","volume":"73","author":[{"given":"Qian","family":"Fu","sequence":"first","affiliation":[{"name":"1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 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