1. Academic Validation
  2. Hydroalcoholic gel of Angelica sinensis polysaccharides promotes wound healing by suppressing ferroptosis through PI3K/AKT/Nrf2 signaling pathway

Hydroalcoholic gel of Angelica sinensis polysaccharides promotes wound healing by suppressing ferroptosis through PI3K/AKT/Nrf2 signaling pathway

  • Phytomedicine. 2026 Apr:153:157962. doi: 10.1016/j.phymed.2026.157962.
Juhong Pei 1 Hongxia Tao 2 Qiuxia Yang 3 Lin Lv 4 Yuxia Ma 1 Lin Han 5
Affiliations

Affiliations

  • 1 School of Nursing, Lanzhou University, Lanzhou, 730000, Gansu, China.
  • 2 School of Nursing, Gansu Medical College, Pingliang, 744000, Gansu, China.
  • 3 Department of Nursing, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, 730050, Gansu, China.
  • 4 Wound and Ostomy Care Center, Gansu Provincial Hospital, Lanzhou, 730000, Gansu, China.
  • 5 School of Nursing, Lanzhou University, Lanzhou, 730000, Gansu, China; Department of Nursing, Gansu Provincial Hospital, Lanzhou, 730000, Gansu, China. Electronic address: [email protected].
Abstract

Background: Angelica sinensis polysaccharide (ASP) exhibits considerable wound-healing properties. However, its clinical application is limited by rapid evaporation in aqueous solution, which shortens its sustained action. In the early stage, we developed a gel-based formulation of ASP (ASP-G). Although ASP-G holds promise as a topical agent, its effects on wound-related Ferroptosis and the underlying mechanisms remain incompletely understood.

Purpose: This study aimed to elucidate the effects and mechanisms of ASP-G in promoting wound healing.

Methods: This study assessed the impact of ASP-G on wound healing in a mouse model of pressure ulcer (PU) in vivo, as well as in endothelial cell lines stimulated with oxygen-glucose deprivation/reoxygenation (OGD/R) or erastin in vitro.

Results: In vivo, ASP-G accelerated wound healing and angiogenesis and showed anti-ferroptosis effect in wound tissues. Meanwhile, key proteins in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathways were upregulated following ASP-G treatment. Proteomic analysis revealed that the differentially expressed proteins were most significantly enriched in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Western blot analysis confirmed that ASP-G treatment increased the phosphorylation levels of PI3K and Akt in wounds of PU mice. In vitro, ASP-G markedly inhibited Ferroptosis induced by OGD/R in endothelial cells, enhanced p-AKT, Nrf2 and heme oxygenase-1 (HO-1) proteins expression, and improved cell migration, proliferation, and tube formation. Notably, these protective effects were abolished through either PI3K inhibition or Nrf2 knockdown.

Conclusions: ASP-G promotes wound healing by suppressing Ferroptosis of endothelial cells through activation of the PI3K/Akt/Nrf2 pathway.

Keywords

Angelica sinensis polysaccharide; Ferroptosis; PI3K/AKT/NrF2 pathway; Wound healing.

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