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
  • 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.
Products