{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:06:06Z","timestamp":1791911166654,"version":"4.3.4"},"reference-count":60,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81973452"],"award-info":[{"award-number":["81973452"]}]},{"name":"National Natural Science Foundation of China","award":["82111530156"],"award-info":[{"award-number":["82111530156"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR\/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR\/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion\/reperfusion (MCAO\/R) as well as H2O2-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H2O2-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2\/NQO-1 and Nrf2\/HO-1 signaling pathway.<\/jats:p>","DOI":"10.3390\/cells14151205","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:25:11Z","timestamp":1754486711000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Purified Cornel Iridoid Glycosides Attenuated Oxidative Stress Induced by Cerebral Ischemia-Reperfusion Injury via Morroniside and Loganin Targeting Nrf2\/NQO-1\/HO-1 Signaling Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhaoyang","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 Taibai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangli","family":"Xue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 Taibai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enjie","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 Taibai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yourui","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 Taibai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiliang","family":"Li","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, Division of Medicine, Faculty of Medical Sciences, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-2485","authenticated-orcid":false,"given":"Boling","family":"Qiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, No. 229 Taibai North Road, Xi\u2019an 710069, China"},{"name":"Shaanxi Traditional Chinese Medicine Innovation Engineering Technology Research Center, No. 229 Taibai North Road, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000487406","article-title":"Apparent diffusion coefficient signal intensity ratio predicts the effect of revascularization on ischemic cerebral edema","volume":"45","author":"Bevers","year":"2018","journal-title":"Cerebrovasc. 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