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Rosavin is the main chemical component of <jats:italic>Rhodiola<\/jats:italic> plants, which exerts anti\u2010oxidative and antiinflammatory effects. In this research, the potential therapeutic effect of rosavin was investigated by the PM2.5\u2010induced lung injury rat model. Rats were instilled with PM2.5 (7.5\u00a0mg\/kg) suspension intratracheally, while rosavin (50\u2009mg\/kg, 100\u2009mg\/kg) was delivered by intraperitoneal injection before the PM2.5 injection. It was observed that rosavin could prevent lung injury caused by PM2.5. PM2.5 showed obvious ferroptosis\u2010related ultrastructural alterations, which were significantly corrected by rosavin. The pretreatment with rosavin downregulated the levels of tissue iron, malondialdehyde, and 4\u2010hydroxynonenal, and increased the levels of glutathione. The expression of nuclear factor E2\u2010related factor 2 (Nrf2) was upregulated by rosavin, together with other ferroptosis\u2010related proteins. RSL3, a specific ferroptosis agonist, reversed the beneficial impact of rosavin. The network pharmacology approach predicted the activation of rosavin on the phosphatidylinositol 3\u2010kinase (PI3K)\/protein kinase B (Akt) signaling pathway. LY294002, a potent PI3K inhibitor, decreased the upregulation of Nrf2 induced by rosavin. In conclusion, rosavin prevented lung injury induced by PM2.5 stimulation and suppressed ferroptosis via upregulating PI3K\/Akt\/Nrf2 signaling pathway.<\/jats:p>","DOI":"10.1002\/ptr.7606","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T02:24:20Z","timestamp":1663035860000},"page":"195-210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Pretreatment with rosavin attenuates PM2.5\u2010induced lung injury in rats through antiferroptosis via PI3K\/Akt\/Nrf2 signaling pathway"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-4176","authenticated-orcid":false,"given":"Yilan","family":"Wang","sequence":"first","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan 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