Hesperetin alleviates PM2.5-induced lung injury by inhibiting ferroptosis in an Nrf2-dependent manner
- Int Immunopharmacol. 2025 Feb 20:148:114123. doi: 10.1016/j.intimp.2025.114123.
- 1. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021 China.
- 2. Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130001 China. Electronic address: [email protected].
- 3. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021 China. Electronic address: [email protected].
Background: Fine particulate matter (PM2.5) is a global environmental problem that threatens public health because it can induce Ferroptosis and cause lung injury. Hesperetin (Hes), a natural compound widely present in fruits and vegetables, can activate nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting powerful antioxidant effects.
Purpose: We explored the antioxidant effects of Hes on lung injury caused by PM2.5 exposure.
Methods: In vivo, a mouse model of PM2.5-induced lung injury was used to evaluate the protective effect of Hes. In vitro, the effects of Hes on PM2.5-induced Ferroptosis were examined in BEAS-2B cells.
Results: In vivo, Hes activated the Nrf2 signaling pathway and protected lung tissues from damage induced by PM2.5. In vitro, Hes activated Nrf2 by promoting PI3K/Akt phosphorylation and inhibiting PM2.5-induced Ferroptosis. However, in siNrf2-treated BEAS-2B cells, the protective effects of Hes were eliminated. In addition, Nrf2-KO mice exhibited more severe lung injury than did wild-type (WT) mice after PM2.5 exposure. Besides, the protective effects of Hes on PM2.5-exposed Nrf2-KO mice were strongly compromised.
Conclusion: Hes activates Nrf2 by promoting PI3K/Akt phosphorylation to exert a protective effect on PM2.5-induced Ferroptosis and lung injury.
-
Cat. No.Product NameDescriptionTargetResearch Area
-
Research Areas: Cancer
-