2. Academic Validation
  3. Sesamin promotes the survival of skin flaps in rats by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway

Sesamin promotes the survival of skin flaps in rats by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway

  • J Ethnopharmacol. 2026 Feb 28:357:120938. doi: 10.1016/j.jep.2025.120938.
Jialong Yang 1,  Hebin Pan 2,  Zhigang Bian 3,  Yiran Wang 4,  Qingyu Chen 5,  Sihan Chen 6,  Kai Chen 7,  Weilong Song 8,  Panshen Xu 9,  An Wang 10,  Jiapeng Deng 11,  Dingsheng Lin 12
Affiliations

Affiliations

  • 1 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 2 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 3 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 4 Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
  • 5 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 6 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 7 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 8 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 9 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 10 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 11 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
  • 12 Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: [email protected].
PMID: 41275941 DOI: 10.1016/j.jep.2025.120938
Abstract

Ethnopharmacological relevance: Skin flaps are widely used in surgery yet remain prone to distal necrosis, making improved survival a significant clinical goal. Sesamin, the primary bioactive component of traditional Chinese medicines Sesamum indicum L. (hu ma) and sesame oil, is known for promoting blood circulation and tonifying essence and blood. While its efficacy against oxidative stress-related pathologies is recognized, its specific impact on FLAP survival has not been elucidated.

Aim of the study: This study investigated the pharmacological effects of sesamin on FLAP survival and its mechanism of action.

Materials and methods: 54 rats undergoing McFarlane FLAP surgery were randomly divided into low-dose (LS), high-dose (HS) sesamin, and Control groups. On postoperative day 3, FLAP tissues were harvested to examine mitochondrial ultrastructure via transmission electron microscopy and to analyze the expression of ferroptosis-related proteins by Western blot. On day 7, FLAP survival rates and blood perfusion were assessed. Histopathological evaluation was performed using hematoxylin and eosin (H&E) staining, while oxidative stress levels were determined by measuring superoxide dismutase (SOD) activity and malondialdehyde (MDA) content with commercial assay kits. Furthermore, the expression levels of VEGF and inflammatory cytokines were detected by immunofluorescence. In vitro experiment, an oxygen-glucose deprivation/reperfusion (OGD/R) model was established using human umbilical vein endothelial cells (HUVECs). To elucidate the core mechanism by which sesamin exerts its pharmacological effects through Nrf2-mediated inhibition of Ferroptosis, the experimental groups included an inhibitor group and a positive Control group treated with Nrf2 inhibitor (ML385) and Ferroptosis inhibitor (Ferrostatin-1), respectively.

Results: Sesamin treatment significantly enhanced FLAP survival, correlating with enhanced angiogenesis and attenuated histopathological damage. It concomitantly alleviated inflammation, as evidenced by reduced levels of TNF-α, IL-1β, and IL-6, and mitigated oxidative stress, indicated by elevated SOD activity and decreased MDA content. Mechanistically, sesamin regulated key ferroptosis-related proteins, demonstrating its ability to suppress Ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway.

Conclusion: Sesamin promotes FLAP survival by enhancing angiogenesis, alleviating oxidative stress and inflammation, and inhibiting Ferroptosis via the Nrf2/SLC7A11/GPX4 axis.

Keywords

Angiogenesis; Ferroptosis; Flap survival; Inflammation; Nrf2/SLC7A11/GPX4 pathway; Sesamin.

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