Research Paper Volume 16, Issue 13 pp 10918—10930

Luteolin targets the AGE-RAGE signaling to mitigate inflammation and ferroptosis in chronic atrophic gastritis

Nailin Zhang1,8, *, , Pingping Chen2, *, , Xiaoyan Liang3, , Jianhui Sun4, , Qiquan Liu5, , Shengjiang Guan6, , Qiao Wang7, ,

  • 1 Clinical Research Base Office, Hebei Provincial Hospital of Chinese Medicine, Hebei, China
  • 2 Department of Pharmacology, Hebei University of Chinese Medicine, Hebei, China
  • 3 Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 4 Hebei Key Laboratory of Turbidity Toxin Syndrome, Hebei University of Chinese Medicine, Hebei, China
  • 5 Department of Spleen and Stomach Diseases, Hebei Provincial Hospital of Chinese Medicine, Hebei, China
  • 6 Pharmaceutical Department, Hebei Provincial Hospital of Chinese Medicine, Hebei, China
  • 7 Pharmacological Analysis Teaching and Research Department, Hebei Medical University, Hebei, China
  • 8 Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, Hebei Provincial Hospital of Chinese Medicine, Hebei, China
* Co-first author

Received: January 23, 2024       Accepted: May 21, 2024       Published: June 24, 2024
How to Cite

Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and precancerous lesion in stomach cancer. Abnormal activation cellular ferroptosis further damages gastric tissue, which is susceptible to inflammation. Luteolin has powerful anti-inflammatory and regulatory potential for cellular ferroptosis. We aimed to clarify the involvement of luteolin in inflammation and ferroptosis during CAG. Luteolin targets were searched to identify intersecting genes in the chronic atrophic gastritis disease database. The AGE-RAGE pathway is a potential target of luteolin for the treatment of chronic atrophic gastritis and a binding site between luteolin and RAGE was predicted through a computer simulation of molecular docking. We established a CAG rat model using N-methyl-N-nitro-N-nitroguanidine. The therapeutic effect of luteolin on CAG was detected using western blotting, qPCR, hematoxylin and eosin staining, lipid oxidation (MDA), and Fe2+ assays. Luteolin inhibited the AGE-RAGE signaling pathway and reduced the inflammatory response in gastric tissues. Additionally, luteolin downregulated the concentration of (MDA) and Fe2+, and CAG downregulated the expression levels of ACSL4 and NOX1 and upregulated the expression levels of FIH1 and GPX4 ferroptosis-related proteins, thus inhibiting the ferroptosis of gastric tissue cells, which had a therapeutic effect on CAG.


CAG: chronic atrophic gastritis; GO: gene ontology; HE: hematoxylin and eosin; KEGG: Kyoto Encyclopedia of Genes and Genomes; PCA: principal component analysis; PPI: protein-protein interaction.