Asiaticoside (AS) has known anti-inflammatory effects in diabetic wounds, but the underlying mechanisms are still unclear. In this study, we reveal that AS alleviates inflammation in diabetic wounds by activating ferroptosis of M1 macrophages, which is attributed to the downregulation of ferroportin 1 and ferritinophagy-induced degradation of ferritin heavy chain 1. Furthermore, AS was encapsulated in gelatin-methacryloyl hydrogels to accelerate diabetic wound healing and shorten the inflammatory period by activating ferroptosis of M1 macrophages in vivo. This study suggests a promising AS-based strategy for treating inflammatory diseases associated with excessive activation of M1
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.
Author list:
Shengnan Cui†, Sheng Meng†, Yong Liu†, Shengqiu Chen, Wenzhi Hu, Qilin Huang, Ziqiang Chu, Weicheng Zhong, Liqian Ma, Zhe Li, Yufeng Jiang*, Xi Liu*, Xiaobing Fu*, Cuiping Zhang*
How to cite:
S. Cui, S. Meng, Y. Liu, S. Chen, W. Hu, Q. Huang, Z. Chu, W. Zhong, L. Ma, Z. Li, Y. Jiang, X. Liu, X. Fu, C. Zhang, Exploration 2025, 20240062.
https://doi.org/10.1002/EXP.20240062