2. Academic Validation
  3. Corilagin attenuates intestinal ischemia/reperfusion injury in mice by inhibiting ferritinophagy-mediated ferroptosis through disrupting NCOA4-ferritin interaction

Corilagin attenuates intestinal ischemia/reperfusion injury in mice by inhibiting ferritinophagy-mediated ferroptosis through disrupting NCOA4-ferritin interaction

  • Life Sci. 2023 Oct 17:122176. doi: 10.1016/j.lfs.2023.122176.
Yunxiang Wang 1,  Bin Li 2,  Guanting Liu 1,  Qipeng Han 1,  Yunpeng Diao 3,  Jing Liu 4
Affiliations

Affiliations

  • 1 College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
  • 2 College of Pharmacy, Dalian Medical University, Dalian, 116044, China; Dalian Anti-Infective Traditional Chinese Medicine Development Engineering Technology Research Center, Dalian 116044, China.
  • 3 College of Pharmacy, Dalian Medical University, Dalian, 116044, China; Dalian Anti-Infective Traditional Chinese Medicine Development Engineering Technology Research Center, Dalian 116044, China. Electronic address: diaoyp@dmu.edu.cn.
  • 4 College of Pharmacy, Dalian Medical University, Dalian, 116044, China; Dalian Anti-Infective Traditional Chinese Medicine Development Engineering Technology Research Center, Dalian 116044, China. Electronic address: liujing8166@dmu.edu.cn.
PMID: 37858718 DOI: 10.1016/j.lfs.2023.122176
Abstract

Aims: Intestinal ischemia reperfusion (II/R) is a common clinical emergency. Ferroptosis is reported to play a role in II/R injury. Our previous studies revealed that corilagin significantly attenuates intestinal ischemia/reperfusion injuries. However, the underlying molecular mechanism is unclear and requires further study.

Materials and methods: DAO, GSSG/T-GSH, MDA, and Fe2+ were assessed by IHC and 4-HNE and 15-LOX were measured by ELISA. Mitochondrial damage was observed by TEM and cellular oxidation levels were detected by C11-BODIPY 581/591 and DHE probes. LC3, p62, Beclin1, ACSL4, GPX4, NCOA4, and ferritin expression were examined by WB in vivo and in vitro. IF, co-IF, q-PCR, and constructed NCOA4-knock-down IEC-6 were used to evaluate the role of NCOA4 in the effect of corilagin against II/R injury. Temporal and nucleoplasmic variations with or without corilagin were observed by WB. Co-IP and molecular docking were used to investigate the NCOA4-ferritin interaction.

Key findings: Corilagin attenuated II/R-induced Ferroptosis both in vitro and in vivo. Further study revealed that the anti-ferroptosis bioactivity of corilagin might be due to the modulation of iron homeostasis via inhibition of ferritinophagy in an NCOA4-dependent manner.

Significance: Corilagin might be a potential therapeutic agent for II/R-induced tissue injury.

Keywords

Corilagin; Corilagin (PubChem CID: 73568); Erastin (PubChem CID: 11214940); Ferritinophagy; Ferroptosis; Ischemia-reperfusion; LY294002 (PubChem CID: 3973); MG-132 (PubChem CID: 462382); NCOA4; Nigericin (PubChem CID: 16760591).

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