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<p>This study aims to investigate the molecular mechanism by which sulfurized garlic (SAC) inhibits ferroptosis through targeting Keap1/Nrf2/GPX4 signaling pathway, thereby restoring intestinal epithelial cell barrier function and alleviating ulcerative colitis (UC). Oxidative stress was induced in cells using H₂O₂ and detected by DCFH-DA. CETSA and Western blotting were employed to assess SAC-target protein binding and antioxidant capacity using DPPH and total antioxidant assays. In <i>vivo</i>, C57BL/6 mice were divided into control, DSS, and SAC groups. DAI was scored based on weight loss, stool consistency, and bleeding. Histology (H&amp;E), IHC (MUC2 and Nrf2), ROS (ELISA), gene expression (qRT-PCR), and protein levels (Western blotting) were analyzed in colon tissues. Serum metabolite profiles were assessed by UHPLC-QTOF-MS for differential metabolite identification and KEGG pathway enrichment. SAC can effectively alleviate UC, which is based on SAC elevating the expression of antioxidant enzymes like GPX4 and NQO1, while reducing ROS and MDA levels. Molecular docking and CETSA analyses revealed that SAC interacts with Keap1 and GPX4 proteins, activating the Keap1/Nrf2/GPX4 pathway. Metabolomics enrichment indicated that SAC modulates the glutathione metabolism pathway by regulating GSH levels, thereby influencing GPX4 stability and activity. SAC can regulate glutathione metabolism through Keap1/Nrf2/GPX4 signaling pathway, inhibit ferroptosis, alleviate intestinal epithelial cell damage, and repair intestinal barrier function.</p>

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SAC regulates glutathione metabolism via the Keap1/Nrf2/GPX4 signaling pathway to inhibit ferroptosis and alleviate ulcerative colitis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月29日

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  • Ximin Wang,
  • Shunan Guo,
  • Jia Zhu,
  • Xianjing Hu,
  • Weibo Dai

摘要

This study aims to investigate the molecular mechanism by which sulfurized garlic (SAC) inhibits ferroptosis through targeting Keap1/Nrf2/GPX4 signaling pathway, thereby restoring intestinal epithelial cell barrier function and alleviating ulcerative colitis (UC). Oxidative stress was induced in cells using H₂O₂ and detected by DCFH-DA. CETSA and Western blotting were employed to assess SAC-target protein binding and antioxidant capacity using DPPH and total antioxidant assays. In vivo, C57BL/6 mice were divided into control, DSS, and SAC groups. DAI was scored based on weight loss, stool consistency, and bleeding. Histology (H&E), IHC (MUC2 and Nrf2), ROS (ELISA), gene expression (qRT-PCR), and protein levels (Western blotting) were analyzed in colon tissues. Serum metabolite profiles were assessed by UHPLC-QTOF-MS for differential metabolite identification and KEGG pathway enrichment. SAC can effectively alleviate UC, which is based on SAC elevating the expression of antioxidant enzymes like GPX4 and NQO1, while reducing ROS and MDA levels. Molecular docking and CETSA analyses revealed that SAC interacts with Keap1 and GPX4 proteins, activating the Keap1/Nrf2/GPX4 pathway. Metabolomics enrichment indicated that SAC modulates the glutathione metabolism pathway by regulating GSH levels, thereby influencing GPX4 stability and activity. SAC can regulate glutathione metabolism through Keap1/Nrf2/GPX4 signaling pathway, inhibit ferroptosis, alleviate intestinal epithelial cell damage, and repair intestinal barrier function.