2. Academic Validation
  3. EGCG activates Keap1/P62/Nrf2 pathway, inhibits iron deposition and apoptosis in rats with cerebral hemorrhage

EGCG activates Keap1/P62/Nrf2 pathway, inhibits iron deposition and apoptosis in rats with cerebral hemorrhage

  • Sci Rep. 2024 Dec 28;14(1):31474. doi: 10.1038/s41598-024-82938-y.
Liang Hao # 1 2,  Aobo Zhang # 1,  Dongsheng Lv 3,  LuLu Cong 1,  Zhimin Sun 2,  Liqiang Liu 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 2 Department of Neurosurgery, The Third Hospital of Shijiazhuang, Shijiazhuang, 050000, Hebei, China.
  • 3 Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
  • 4 Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. 27400950@hebmu.edu.cn.
  • # Contributed equally.
PMID: 39732956 DOI: 10.1038/s41598-024-82938-y
Abstract

Intracerebral hemorrhage (ICH) is a common cerebrovascular disease characterized by a high incidence, disability rate, and mortality. Epigallocatechin gallate (EGCG), a key catechin compound found in green tea, has received increasing attention for its potential neuroprotective and therapeutic effects in neurological disorders. Studies have indicated that EGCG may influence various signaling pathways and molecular targets, including the inhibition of oxidative stress, reduction of inflammatory responses, suppression of cell Apoptosis, regulation of cell survival, and enhancement of Autophagy. Although the exact mechanism of action of EGCG is not fully understood, it has become a focal point of research in various disciplines due to its promising potential. This study aims to investigate the effects of EGCG on oxidative stress, iron deposition, and cell Apoptosis in rats with ICH, as well as to uncover the underlying mechanisms. An ICH rat model was created to simulate cerebral hemorrhage, while an in vitro model utilizing primary cortical neurons was developed. The neurons were pre-treated with EGCG before being exposed to Erastin and RSL3 to induce iron death. The levels of oxidative stress, iron deposition, and cell Apoptosis were evaluated in both models. In the ICH model, EGCG was discovered to enhance the activation of the Keap1/p62/Nrf2 signaling pathway in both in vivo and in vitro studies. Furthermore, EGCG significantly elevated the levels of GPX4 and XCT proteins, as well as the nuclear expression of Nrf2. It was noted that the Nrf2 inhibitor ML385 partially decreased the expression of these proteins. Through the activation of the Keap1/p62/Nrf2 pathway, EGCG inhibits inflammation, oxidative stress and iron deposition in rats with cerebral hemorrhage. EGCG inhibits oxidative stress, iron deposition and Apoptosis in rats with ICH by activating Keap1/p62/Nrf2 pathway.

Keywords

Cell apoptosis; EGCG; Ferroptosis; Intracerebral hemorrhage; Oxidative stress.

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