2. Academic Validation
  3. Folic acid alleviates endothelial dysfunction caused by T2DM-induced ferroptosis by activating the SIRT6/NRF2/GPX4 signaling pathway

Folic acid alleviates endothelial dysfunction caused by T2DM-induced ferroptosis by activating the SIRT6/NRF2/GPX4 signaling pathway

  • Food Funct. 2026 Apr 27;17(8):3587-3599. doi: 10.1039/d5fo04381f.
Lei Hong 1 2 3,  Xinqi Lou 1 2 3,  Yingjie Zha 1 2 3,  Xuejie Fu 1 2 3,  Tuanjie Che 2 4,  Shigang Qiao 1 2 5 6,  Chen Wang 3,  Jianzhong An 1 2 3
Affiliations

Affiliations

  • 1 Institute of Clinical Medicine Research, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China. [email protected].
  • 2 Suzhou Science and Technology Town Hospital, No. 1 Lijiang Road, Suzhou 215153, China.
  • 3 Medical Research Center of Suzhou, School of Medicine, Nanjing University, China. [email protected].
  • 4 Laboratory of Precision Medicine and Translational Medicine, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
  • 5 Department of Anesthesiology, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, Jiangsu 215300, China.
  • 6 Gansu Key Laboratory of Functional Genomics and Molecular Diagnosis, Lanzhou 730000, China.
PMID: 41906715 DOI: 10.1039/d5fo04381f
Abstract

Cardiovascular complications associated with type 2 diabetes mellitus (T2DM) pose a serious threat to human health. Folic acid deficiency is associated with various diseases, including atherosclerosis. However, it remains unclear whether folic acid has a protective effect on vascular injury induced by T2DM. To address this, folic acid was administered to db/db or db/dm mice, and endothelial cells were treated under high-fat and high-glucose (HGF) conditions to evaluate the effect of folic acid on cell viability. RNA Sequencing was performed to explore the potential targets of folic acid. The results indicated that folic acid alleviates endothelial cell injury and Ferroptosis in T2DM by upregulating the SIRT6/NRF2 pathway and mitigating oxidative stress, Fe2+ accumulation and lipid peroxidation. The SIRT6 Inhibitor counteracted the protective effect of folic acid on endothelial cells in vitro. Overall, folic acid may be a promising drug for treating or alleviating endothelial dysfunction in T2DM.

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