{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:48Z","timestamp":1785437988461,"version":"3.56.0"},"reference-count":74,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cerebral ischemia reperfusion (CIR) is a condition of brain, which is occurred due to insufficient supply of blood. Isofraxidin is a naturally occurring coumarin derivative which showed the strong anti\u2010inflammatory and antioxidant\u2002effect in various disease animal models. Its neuroprotective effects against ischemia\/reperfusion (I\/R)\u2010mediated injuries,\u2002however, have not been investigated. The current study was to scrutinize the neuroprotective effect of Isofraxidin against the CIR in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Swiss Albino Wistar rats (sex\u2010male, 42 rats) were randomly selected for this study and transient occlusion of the middle cerebral artery was performed (1\u2009h) for the induction of ischemia followed by reperfusion (24\u2009h). Neurological score, brain water content, brain edema, infarct volume, nitric oxide (NO), myeloperoxidase (MPO), evans blue leakage, antioxidant, inflammatory, cytokines parameters and matrix metalloproteinases (MMP) level were estimated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Isofraxidin (7.5, 15 and 30\u2009mg\/kg) suppressed the brain edema (56.93%, 33.92%, 12.9%) neurological score (3.37, 2.76, 1.5), infarct volume (40.43%, 23.08%, 13.02%), evans blue leakage (4.32\u2009\u03bcg\/g tissue, 2.68\u2009\u03bcg\/g tissue, 1.35\u2009\u03bcg\/g tissue) and brain water content (72.95%, 54.66%, 40.38%) in the CIR group rats. CIR rats treated with Isofraxidin (7.5, 15 and 30\u2009mg\/kg) significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) altered the level of clusterin (305.17\u2009\u03bcg\/mL, 197\u2009\u03bcg\/mL, 110.65\u2009\u03bcg\/mL), neuron\u2010specific enolase (14.04\u2009ng\/mL, 8.08\u2009ng\/mL, 6.02\u2009ng\/mL), NO (0.78 \u03bcmol\/mg, 0.51 \u03bcmol\/mg, 0.39 \u03bcmol\/mg) and MPO (1.81 U\/mg protein, 1.41 U\/mg protein, 0.87 U\/mg protein) along with the modulation of antioxidant parameters. Isofraxidin (7.5, 15 and 30\u2009mg\/kg) significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) altered the level of cytokines such as tumor necrosis factor\u2010\u03b1 (29.53\u2009pg\/mg, 19.55\u2009pg\/mg, 11.52\u2009pg\/mg), interleukin\u20101\u03b2 (19.22\u2009pg\/mg, 12.36\u2009pg\/mg, 7.01\u2009pg\/mg), 2 (234.33\u2009pg\/mg, 151.66\u2009pg\/mg, 71.27\u2009pg\/mg), 6 (37.23\u2009pg\/mg, 30.55\u2009pg\/mg, 21.91\u2009pg\/mg), 9 (89.06\u2009pg\/mg, 48.51\u2009pg\/mg, 26.29\u2009pg\/mg) and 10 (10.98\u2009pg\/mg, 19.38\u2009pg\/mg, 28.86\u2009pg\/mg). CIR group rats treated with isofraxidin (7.5, 15 and 30\u2009mg\/kg) decreased the level of cyclooxygenase\u20102 (32.05\u2009pg\/mg, 19.91\u2009pg\/mg, 12.83\u2009pg\/mg), prostaglandin (33.88\u2009pg\/mg, 21.01\u2009pg\/mg, 12.13\u2009pg\/mg), inducible nitric oxide (31.01\u2009pg\/mg, 19.51\u2009pg\/mg, 10.16\u2009pg\/mg), vascular endothelial growth factor (41.71\u2009pg\/mg, 28.55\u2009pg\/mg, 16.19\u2009pg\/mg) and nuclear kappa B factor (52.91\u2009pg\/mg, 36.16\u2009pg\/mg, 16.17\u2009pg\/mg), respectively. Isofraxidin (7.5, 15 and 30\u2009mg\/kg) treatment altered the mRNA expression of COX\u20102, LOX\u20101, iNOS, NF\u2010\u03baB, Bax, Bcl\u20102, caspase\u20103, TRL4, syndecan\u20101, CSF, aquaportin\u20101, OCT3 and RFX1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Isofraxidin treatment exhibited brain protective against cerebral ischemia reperfusion via suppression of free radical and inflammatory reaction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70555","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:37:29Z","timestamp":1761896249000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Isofraxidin Attenuates Ischemia\/Reperfusion\u2010Induced Neuroinflammation and Oxidative Stress Via Modulation of the 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