2. Academic Validation
  3. Activating Ferroptosis of M1 Macrophages: A Novel Mechanism of Asiaticoside Encapsuled in GelMA for Anti-Inflammation in Diabetic Wounds

Activating Ferroptosis of M1 Macrophages: A Novel Mechanism of Asiaticoside Encapsuled in GelMA for Anti-Inflammation in Diabetic Wounds

  • Exploration (Beijing). 2025 Oct 31;5(6):20240062. doi: 10.1002/EXP.20240062.
Shengnan Cui 1 2,  Sheng Meng 1,  Yong Liu 3,  Shengqiu Chen 4,  Wenzhi Hu 1 5 6,  Qilin Huang 1,  Ziqiang Chu 1,  Weicheng Zhong 1,  Liqian Ma 1 5 6,  Zhe Li 7,  Yufeng Jiang 8,  Xi Liu 1 5 6,  Xiaobing Fu 1 5 6,  Cuiping Zhang 1 5 6
Affiliations

Affiliations

  • 1 Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing China.
  • 2 Department of Dermatology The Second Affiliated Hospital Shaanxi University of Chinese Medicine Xianyang Shaanxi China.
  • 3 Department of Dermatology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China.
  • 4 Innovation Research Center for Diabetic Foot West China Hospital Sichuan University Chengdu China.
  • 5 PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury Repair and Regeneration Beijing China.
  • 6 Research Unit of Trauma Care Tissue Repair and Regeneration Chinese Academy of Medical Sciences Beijing China.
  • 7 Burns Unit Concord Hospital University of Sydney Medical School Sydney Australia.
  • 8 Department of Tissue Regeneration and Wound Repair PLA General Hospital Beijing China.
PMID: 41476651 DOI: 10.1002/EXP.20240062
Abstract

Diabetic wounds are characterized by chronic inflammation, partly due to the persistent accumulation of pro-inflammatory M1 macrophages. Asiaticoside (AS), a triterpenoid extracted from Centella asiatica, has known anti-inflammatory effects in several diseases, but the underlying mechanisms in diabetic wounds are still unclear. This study reveals that AS alleviates inflammation in diabetic wounds by activating Ferroptosis of M1 macrophages. In vitro, AS reduces the number of M1 macrophages in a high glucose microenvironment and their secretion of proinflammatory cytokines with concurrent induction of Ferroptosis. Further investigation shows that AS-activated Ferroptosis is attributed to the downregulation of Ferroportin 1 (FPN1) and ferritinophagy-induced degradation of ferritin heavy chain 1 (FTH1), which together increase the amount of intracellular free ferrous ions (Fe2+). In vivo, AS-encapsulated gelatin-methacryloyl hydrogels accelerates diabetic wound healing and shortens the inflammatory period by activating Ferroptosis of M1 macrophages with the reduced expression of FPN1 and FTH1. These results suggest a promising AS-based strategy for treating inflammatory diseases associated with excessive activation of M1 macrophages.

Keywords

anti‐inflammation; asiaticoside; diabetic wounds; ferroptosis; macrophages.

Figures
Products