{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:18:25Z","timestamp":1788337105881,"version":"build-2803163510"},"reference-count":34,"publisher":"World Scientific Pub Co Pte Ltd","issue":"06","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82474352"],"award-info":[{"award-number":["82474352"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation of China","doi-asserted-by":"crossref","award":["2025JJ90026"],"award-info":[{"award-number":["2025JJ90026"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hunan Provincial Health and Family Planning Commission Project","award":["B202303079716"],"award-info":[{"award-number":["B202303079716"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Chin. Med."],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Panax notoginseng saponins (PNS), the chief saponin components of the traditional Chinese medicine Panax notoginseng, are known to ameliorate the outcomes of ischemic stroke (IS), primarily by mitigating inflammatory responses, enhancing microcirculation, and modulating oxidative stress. Damage to brain microvascular endothelial cells (BMECs) and BMECs\u2019 ferroptosis are critical steps in cerebral ischemia-reperfusion injury (CIRI), a process in which neutrophil extracellular traps (NETs) have been shown to induce BMECs injury, thereby aggravating CIRI. We aimed to investigate the regulatory effects of PNS on NETs and BMECs\u2019 ferroptosis following CIRI and evaluate its therapeutic efficacy in brain injury intervention. In this study, Sprague-Dawley rats were subjected to middle cerebral artery occlusion\/reperfusion (MCAO\/R), and the BMECs were exposed to oxygen-glucose deprivation\/reoxygenation (OGD\/R). These models were pretreated with PNS or the NETs-degrading agent DNase I, and the ensuing changes in key proteins, NETs-related markers, inflammatory factors, and ferroptosis-related indicators were assessed using Western Blotting or specific assay kits. Finally, neurological injury was assessed by neurological function scores and triphenyl tetrazolium chloride staining, while cell viability was evaluated using the Cell Counting Kit-8 (CCK-8) assay. In the rat models, PNS and DNase I markedly reduced the levels of key NETs biomarkers, related inflammatory factors, as well as MCAO\/R-triggered ferroptosis, thereby mitigating brain injury. PNS treatment effectively suppressed NETs-induced ferroptosis in BMECs in\u00a0vitro, thereby alleviating cell injury. This study demonstrated that PNS alleviates CIRI by inhibiting NETs and BMECs\u2019 ferroptosis. Mechanistically, PNS suppresses NETs, thereby suppressing ferroptosis. Collectively, these findings support a pharmacological rationale underlying the clinical treatment of IS.<\/jats:p>","DOI":"10.1142\/s0192415x26500679","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:43:52Z","timestamp":1787240632000},"page":"1807-1821","source":"Crossref","is-referenced-by-count":0,"title":["<i>Panax notoginseng<\/i>\n                    Saponins Attenuate Cerebral Ischemia-Reperfusion Injury by Suppressing Neutrophil Extracellular Traps and Ferroptosis in Brain Microvascular Endothelial Cells"],"prefix":"10.1142","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-948X","authenticated-orcid":false,"given":"Qian","family":"Xiao","sequence":"first","affiliation":[{"name":"Basic Research Center of Integrated Chinese and Western Medicine for Prevention and Treatment of Vascular Diseases, Hunan University of Chinese Medicine, Changsha, 410208 Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1573-4063","authenticated-orcid":false,"given":"Xin-Quan","family":"Deng","sequence":"additional","affiliation":[{"name":"Basic Research Center of Integrated Chinese and Western Medicine for Prevention and Treatment of Vascular Diseases, Hunan University of Chinese Medicine, Changsha, 410208 Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1185-5592","authenticated-orcid":false,"given":"Biao","family":"Tang","sequence":"additional","affiliation":[{"name":"Basic Research Center of Integrated Chinese and Western Medicine for Prevention and Treatment of Vascular Diseases, Hunan University of Chinese Medicine, Changsha, 410208 Hunan, China"},{"name":"People\u2019s Hospital of Ningxiang City, Hunan University of Chinese Medicine, Changsha, 410600 Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"219","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"S0192415X26500679BIB001","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.70385"},{"key":"S0192415X26500679BIB002","doi-asserted-by":"publisher","DOI":"10.1177\/17474930241267353"},{"key":"S0192415X26500679BIB003","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102906"},{"key":"S0192415X26500679BIB004","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00703-5"},{"key":"S0192415X26500679BIB005","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2026.151045"},{"key":"S0192415X26500679BIB006","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01563-4"},{"key":"S0192415X26500679BIB007","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116621"},{"key":"S0192415X26500679BIB007a","doi-asserted-by":"publisher","DOI":"10.1177\/17474930241308142"},{"key":"S0192415X26500679BIB008","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01379-8"},{"key":"S0192415X26500679BIB009","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.26.4.627"},{"key":"S0192415X26500679BIB010","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1287857"},{"key":"S0192415X26500679BIB011","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14634"},{"key":"S0192415X26500679BIB012","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-050823-094312"},{"key":"S0192415X26500679BIB013","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14916"},{"key":"S0192415X26500679BIB014","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.141110"},{"key":"S0192415X26500679BIB015","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgad011"},{"key":"S0192415X26500679BIB016","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16191-y"},{"key":"S0192415X26500679BIB017","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0747-x"},{"key":"S0192415X26500679BIB018","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.070487"},{"key":"S0192415X26500679BIB019","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1488317"},{"key":"S0192415X26500679BIB020","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118639"},{"key":"S0192415X26500679BIB021","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03382-x"},{"key":"S0192415X26500679BIB022","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.97150"},{"key":"S0192415X26500679BIB023","first-page":"e2308719","volume":"11","author":"Mu Q.","year":"2024","journal-title":"Adv. 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