2. Academic Validation
  3. Hesperetin alleviates PM2.5-induced lung injury by inhibiting ferroptosis in an Nrf2-dependent manner

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.
Lu Wang 1,  Ying Tang 1,  Tianhua Hou 1,  Yun Gao 1,  Xinxin Ci 2,  Liping Peng 3
Affiliations

Affiliations

  • 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: cixinxin@jlu.edu.cn.
  • 3 Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021 China. Electronic address: penglp@jlu.edu.cn.
PMID: 39884081 DOI: 10.1016/j.intimp.2025.114123
Abstract

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.

Keywords

Ferroptosis; Hesperetin; Lung injury; Nrf2; PM2.5.

Figures
Products