2. Academic Validation
  3. Galangin Mitigates Alcohol-Induced Intestinal Damage by Suppressing Ferroptosis via the SESN2/KEAP1/NRF2 Pathway in Mice and Caco-2 Cells

Galangin Mitigates Alcohol-Induced Intestinal Damage by Suppressing Ferroptosis via the SESN2/KEAP1/NRF2 Pathway in Mice and Caco-2 Cells

  • J Agric Food Chem. 2026 Feb 11;74(5):4781-4796. doi: 10.1021/acs.jafc.5c11761.
Yanan Zhao 1 2 3 4 5 6,  Rui Wang 1 2 3 4 5,  Ziyang Huang 1 2 3 4 5,  Siting Ju 1 2 3 4 5,  Binghua Dong 1 2 3 4 5,  Hui Teng 1 2 3 4 5,  Lei Chen 1 2 3 4 5 6
Affiliations

Affiliations

  • 1 College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524000, Guangdong, People's Republic of China.
  • 2 Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Zhanjiang524000, Guangdong, People's Republic of China.
  • 3 Guangdong Provincial Engineering Laboratory for Marine Biological Products, Zhanjiang 524000, Guangdong, People's Republic of China.
  • 4 Guangdong Provincial Engineering Technology Research Center of Seafood, Zhanjiang 524000, Guangdong, People's Republic of China.
  • 5 Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institutions, Zhanjiang 524000, Guangdong, People's Republic of China.
  • 6 Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, China.
PMID: 41605867 DOI: 10.1021/acs.jafc.5c11761
Abstract

The gut is often referred to as the "second brain" and is highly vulnerable to alcohol exposure. Galangin, a flavonoid extracted from traditional medicinal herbs, Alpinia officinarum Hance, has manifested auspicious clinical application potential. This study aims to explore the regulatory effect of galangin on Ferroptosis in an alcohol-related intestinal injury model and its underlying mechanism. In vivo, we confirmed that galangin administration could alleviate alcohol-induced iron metabolism dysfunction and Ferroptosis and activate the SESN2/KEAP1/NRF2 signaling pathway in mice colon. In vitro, alcohol-caused disruption of iron homeostasis and Ferroptosis could also be significantly reduced by galangin. Using specific small interfering RNA targeting SESN2 (Si-SESN2) or the NRF2 inhibitor ML385 significantly abrogated the protective effect of galangin. Molecular docking and Co-IP results further revealed that galangin activates NRF2 nuclear translocation by promoting KEAP1/SESN2 formation as well as KEAP1/NRF2 dissociation. Collectively, galangin suppressed Ferroptosis by activating the SESN2/KEAP1/NRF2 pathway in mice and Caco-2 cells.

Keywords

KEAP1; NRF2; SESN2; alcohol; ferroptosis; galangin; intestinal damage.

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