2. Academic Validation
  3. Puerarin Attenuates Iron Overload-Induced Ferroptosis in Retina through a Nrf2-Mediated Mechanism

Puerarin Attenuates Iron Overload-Induced Ferroptosis in Retina through a Nrf2-Mediated Mechanism

  • Mol Nutr Food Res. 2024 Jan 9:e2300123. doi: 10.1002/mnfr.202300123.
Qiongtao Song 1 2 3 4,  Wenyuan Jian 1 2 3 4,  Yuanyuan Zhang 5,  Qiang Li 1 2 3 4,  Ying Zhao 1 2 3,  Rong Liu 1,  Yan Zeng 1,  Fuwen Zhang 1 2 3 4,  Junguo Duan 1 2 3 4
Affiliations

Affiliations

  • 1 Eye School of Chengdu University of TCM, No.37 Twelve Bridge Road, Chengdu, Sichuan, 610075, China.
  • 2 Ineye Hospital of Chengdu University of TCM, No.8 Xinghui Road, Chengdu, Sichuan, 610084, China.
  • 3 Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection, No.37 Twelve Bridge Road, Chengdu, Sichuan, 610075, China.
  • 4 Guangzhou Ineye Vision Health Innovation Institute, No.2 Fenghuang 3rd Road, Guangzhou, Guangdong, 510555, China.
  • 5 Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, No.326 Xinshi South Road, Shijiazhuang, Hebei, 050200, China.
PMID: 38196088 DOI: 10.1002/mnfr.202300123
Abstract

Scope: Age-related increases in retinal iron are involved in the development of retinal degeneration. The recently discovered iron-dependent mechanism of cell death known as Ferroptosis has been linked to a wide range of pathologies. However, its role in iron overload-induced retinal degeneration is still uncertain. Puerarin has been associated with retinal protection. The purpose of this research is to determine how puerarin prevents retinal Ferroptosis under iron overload conditions.

Methods and results: Models of iron overload in Kunming mice, 661W cell, and ARPE-19 cell are established. Increased iron deposition significantly worsens retinal pathology, decreases cell viability, and induces ferroptotic changes. Puerarin mitigates iron overload-induced Ferroptosis by decreasing excessive iron through the regulation of iron handling proteins and lowering lipid peroxidation through the inhibition of cyclooxygenase 2 expression and activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and downstream ferroptosis-related proteins (solute carrier family 7 member 11, Glutathione Peroxidase 4 and heme oxygenase-1). The protective effect of puerarin on Ferroptosis is diminished by the Nrf2-specific inhibitor ML385.

Conclusion: These findings suggest targeting Ferroptosis may be a novel strategy for the management of retinal degeneration. Puerarin may exert some of its ocular benefits by attenuating Ferroptosis.

Keywords

Nrf2; Puerarin; ferroptosis; iron overload; retinal degeneration.

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