{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:19:56Z","timestamp":1788311996380,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dicle University Scientific Research Committee","award":["TIP.26.037"],"award-info":[{"award-number":["TIP.26.037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Objective: Cerebral ischemia\/reperfusion (I\/R) injury triggers oxidative stress, neuroinflammation, neuronal degeneration, and white matter damage not only in directly affected cerebral regions but also in remote brain areas such as the cerebellum. Skimmianine, a naturally occurring furoquinoline alkaloid, has been reported to possess antioxidant and anti-inflammatory properties. This study investigated the protective effects of skimmianine pretreatment against secondary cerebellar injury following experimental cerebral I\/R. Materials and Methods: Thirty-two female Wistar rats were randomly assigned to sham, Skimmianine, I\/R, and I\/R + Skimmianine groups (n = 8\/group). Cerebral I\/R was induced by transient middle cerebral artery occlusion for 60 min followed by 23 h reperfusion. Skimmianine (40 mg\/kg\/day, intraperitoneally) was administered for 14 days before ischemia induction. Oxidative stress markers, neuroinflammatory mediators, histopathological alterations, behavioral outcomes, and ultrastructural changes were evaluated. In addition, network pharmacology and molecular docking analyses were performed to explore potential molecular mechanisms. Results: Cerebral I\/R significantly decreased TAS levels compared with sham (0.89 \u00b1 0.15 vs. 1.52 \u00b1 0.18 mmol Trolox Eq\/L) and increased TOS (15.60 \u00b1 3.03 vs. 6.80 \u00b1 1.41 \u00b5mol H2O2 Eq\/L), OSI (17.48 \u00b1 0.50 vs. 4.43 \u00b1 0.47), TNF-\u03b1 (68.4 \u00b1 10.2 vs. 18.6 \u00b1 4.4 pg\/mL), Iba1 (41.3 \u00b1 9.7 vs. 11.7 \u00b1 1.6 pg\/mL), and GFAP levels (334.5 \u00b1 12.5 vs. 87.7 \u00b1 9.5 ng\/mL; all p &lt; 0.001). I\/R also impaired motor performance, as shown by increased beam crossing time (11.7 \u00b1 2.2 vs. 4.8 \u00b1 0.7 s) and grid foot fault rate (18.6 \u00b1 4.0% vs. 3.4 \u00b1 1.1%). Skimmianine pretreatment significantly improved these alterations, increasing TAS to 1.29 \u00b1 0.20 mmol Trolox Eq\/L and reducing TOS, OSI, TNF-\u03b1, Iba1, and GFAP levels to 9.20 \u00b1 2.04, 7.07 \u00b1 0.47, 34.9 \u00b1 7.4, 24.2 \u00b1 6.9, and 237.0 \u00b1 7.9, respectively, compared with the untreated I\/R group. Histopathological scores for Purkinje cell loss, edema, vascular congestion, and TNF-\u03b1 expression were also significantly reduced by skimmianine. Quantitative TEM analysis showed that I\/R reduced myelin thickness (0.29 \u00b1 0.05 vs. 0.53 \u00b1 0.07 \u00b5m), increased G-ratio values (0.75 \u00b1 0.05 vs. 0.63 \u00b1 0.04), and increased vacuolized fibers (24.70 \u00b1 4.20% vs. 3.20 \u00b1 1.10%), whereas skimmianine partially restored myelin thickness (0.42 \u00b1 0.07 \u00b5m), reduced the G-ratio (0.68 \u00b1 0.05), and decreased vacuolized fibers (11.20 \u00b1 2.80%; p &lt; 0.05 vs. I\/R). Molecular docking demonstrated favorable binding between skimmianine and TNF-\u03b1, with a predicted binding energy of \u22126.953 kcal\/mol. Conclusions: These findings indicate that skimmianine exerts neuroprotective effects against secondary cerebellar injury following cerebral I\/R through coordinated modulation of oxidative stress, systemic neuroinflammatory responses, astroglial injury-associated pathways, and inflammation-related mechanisms.<\/jats:p>","DOI":"10.3390\/antiox15060743","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:22:56Z","timestamp":1781684576000},"page":"743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Skimmianine Pretreatment Attenuates Cerebellar Neuroinflammation and Myelin Injury Following Experimental Cerebral Ischemia\u2013Reperfusion"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-9146","authenticated-orcid":false,"given":"F\u0131rat","family":"A\u015f\u0131r","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"G\u00f6kalp \u00d6zkorkmaz","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, \u00c7ubuk, 06760 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Yal\u00e7\u0131n","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Diyarbak\u0131r Gazi Ya\u015fargil Training and Research Hospital, Health Sciences University, 21070 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u0131rat","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Division of Infertility, Turan \u00c7etin In-Vitro Fertilization Center, \u00c7ukurova, 01360 Adana, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-4022","authenticated-orcid":false,"given":"Tu\u011fcan","family":"Korak","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Medical Faculty, Kocaeli University, 41380 Kocaeli, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Luo, B., Shang, T., Wei, Z., and Zou, W. 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