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Notoginsenoside R1 (NGR1), a bioactive component extracted from the traditional herb Panax notoginseng has been widely applied in the therapy of cardiovascular diseases and neurological disorders. This study aims to investigate the effects of NGR1 on oxidative damage following ICH. Methods: NGR1 was administrated to a collagenase-induced ICH mouse model and hemin-stimulated primary astrocytes in vitro. Hematoma volume, brain water content and neurobehavioral outcomes were assessed in the ICH mice. Cell viability was evaluated using the Cell Counting Kit-8 (CCK-8) assay. In astrocytes pretreated with 25 \u03bcM NGR1 for 24 h followed by 30 \u03bcM hemin treatment for 24 h, levels of reactive oxygen species (ROS), malondialdehyde (MDA), and the glutathione (GSH)\/oxidized glutathione (GSSG) ratio were measured. The expression of lipocalin-2 (LCN2), heme oxygenase-1 (HO-1), and glial fibrillary acidic protein (GFAP) was detected via immunofluorescence staining and Western blotting. Additionally, LCN2 and HO-1 were knocked down in astrocytes, using small interfering RNA (siRNA) transfection. Results: LCN2, HO-1, and GFAP expression was upregulated in the peri-lesional area of the brain following ICH. NGR1 alleviated brain injury and improved neurological function in the collagenase-induced ICH mouse model. Specifically, administration of 20 mg\/kg NGR1 suppressed the upregulation of LCN2 and increased HO-1 expression post ICH. NGR1 enhanced cell viability and reversed hemin-induced toxicity in astrocytes in vitro. Treatment with 25 \u03bcM NGR1 reduced ROS and MDA levels and upregulated the GSH\/GSSG ratio in astrocytes exposed to 30 \u03bcM hemin. Furthermore, 25 \u03bcM NGR1 inhibited LCN2 and GFAP expression while promoting HO-1 expression in hemin-treated astrocytes. The inhibitory effect of NGR1 on LCN2 was reversed by the Nrf-2\/HO-1 inhibitor ML385. Moreover, LCN2 knockdown promoted HO-1 expression and suppressed ROS levels in astrocytes. Conversely, HO-1 knockdown increased LCN2 and GFAP expression, thereby reversing the protective effects of NGR1. Conclusions: This study demonstrates that NGR1 alleviates ICH-induced oxidative damage by promoting HO-1 expression and inhibiting LCN2 expression, thereby maintaining redox homeostasis.<\/jats:p>","DOI":"10.3390\/brainsci16090958","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:27:21Z","timestamp":1789036041000},"page":"958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Notoginsenoside R1 Attenuates Oxidative Damage After Intracerebral Hemorrhage by Inhibiting LCN2 and Promoting HO-1 in Astrocytes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8540-7543","authenticated-orcid":false,"given":"Qingyun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5391-0364","authenticated-orcid":false,"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1072-4283","authenticated-orcid":false,"given":"Baofeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yuhao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7543-5066","authenticated-orcid":false,"given":"Liuguan","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.121.319949","article-title":"Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions","volume":"130","author":"Girard","year":"2022","journal-title":"Circ. 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