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Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SAH was modeled in vivo through filament perforation in male C57BL\/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2\/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2\/GPX4 and FSP1\/CoQ10 pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-024-03099-3","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T12:02:03Z","timestamp":1714737723000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation"],"prefix":"10.1186","volume":"21","author":[{"given":"Junhui","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"3099_CR1","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1001\/jamaneurol.2019.0006","volume":"76","author":"N Etminan","year":"2019","unstructured":"Etminan N, Chang HS, Hackenberg K, de Rooij NK, Vergouwen MDI, Rinkel GJE, Algra A. 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