{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T15:01:34Z","timestamp":1775833294580,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech and App Biochem"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Senkyunolide I (Sen I) has a protective effect on the blood\u2013brain barrier (BBB) in rats with sepsis\u2010associated encephalopathy (SAE). This study investigated whether Sen I regulates Nrf2 to ameliorate sepsis\u2010induced brain dysfunction (SIBD). Sixty rats were randomly assigned into Sham group, SAE group (Model group), SAE\u00a0+\u00a0Sen I group (72\u00a0mg\/kg, Sen I group), and SAE+ positive control group (RTA 402, Nrf2 receptor agonist, RTA 402 group), with 15 rats in each group. The cecal ligation and puncture (CLP) method was applied to induce sepsis in rats. SAE modeling was verified 6\u00a0h after operation. The drug was administered 24\u00a0h after surgery. Six rats in each group were sacrificed 24\u00a0h after administration, with brains extracted. The remaining rats would continue to be observed for their survival status until 72\u00a0h post\u2010surgery. Brain cell apoptosis was measured using TUNEL. We detected the expression of glial fibrillary acidic protein (GFAP) by immunofluorescence, <jats:italic>Nrf2<\/jats:italic> gene expression by RT\u2010qPCR, and the protein expression of Nrf2, MMP\u20109, AQP\u20104, and occludin by Western blot. TNF\u2010\u03b1 and IL\u20101\u03b2 levels were tested by ELISA, and malondialdehyde (MDA) and glutathione peroxidase (GSH\u2010Px) by biochemical tests. Survival rate at 72\u00a0h post\u2010surgery, Sham group was 100%. The survival rate of the Sen I group (44.4%) and the RTA 402 group (55.6%) is significantly higher than that of the Model group (11.1%). Both Sen I and RTA 402 can improve the brain tissue damage in rats caused by sepsis, specifically by reducing apoptosis and GFAP expression, reducing TNF\u2010\u03b1, IL\u20101\u03b2, and MDA levels, increasing the activity of GSH\u2010Px, downregulating the protein expression of MMP\u20109 and AQP\u20104, and upregulating the protein expression of Nrf2 and occludin. Moreover, Sen I significantly increased the expression of Nrf2 in rat brain tissues. Sen I ameliorates SIBD in rats by regulating the expression of Nrf2 and astrocyte activation.<\/jats:p>","DOI":"10.1002\/bab.2748","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:20:27Z","timestamp":1744676427000},"page":"1385-1394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Senkyunolide I Improves Septicemia\u2010Induced Brain Dysfunction via Regulating Nrf2 and Astrocyte Activity."],"prefix":"10.1002","volume":"72","author":[{"given":"Haohao","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Wuhan Fourth Hospital  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Wuhan Fourth Hospital  Wuhan Hubei 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