Angelica dahurica extract mitigates oxidative stress and apoptosis to promote flap survival via the ERK1/2-Nrf2 signaling pathway.

BACKGROUND

Flap necrosis remains a significant complication in reconstructive surgery. Angelica dahurica, a traditional medicinal herb, has demonstrated protective effects in various disease models. However, its role in flap survival and the underlying mechanisms remain unclear. This study aimed to evaluate the therapeutic effects and underlying mechanisms of Angelica dahurica extract (AD) on skin flap survival in rats.

MATERIALS: In silico analyses predicted interactions among bioactive compounds, targets, and signaling pathways. A modified McFarlane flap model was established in Sprague-Dawley rats, followed by administration of AD at different doses. An ERK1/2 inhibitor was used to verify pathway involvement. On postoperative day 7, flap survival area and blood perfusion were assessed. Hematoxylin-eosin staining evaluated neutrophil infiltration and microvascular density. Oxidative stress was measured by SOD activity and MDA levels. Protein expression related to signaling, apoptosis, and inflammation was analyzed by immunofluorescence and Western blotting.

RESULTS

AD significantly improved flap viability, increased blood perfusion, and promoted neovascularization. It reduced pro-inflammatory cytokine levels, attenuated oxidative injury, and inhibited apoptosis. Mechanistically, these effects were associated with activation of the ERK1/2-Nrf2 signaling pathway. Inhibition of ERK1/2 attenuated these protective effects, confirming its central role in mediating the response.

CONCLUSIONS

AD enhances skin flap survival by mitigating inflammation and oxidative stress, inhibiting apoptosis, and promoting angiogenesis. Collectively, these findings suggest that AD has considerable therapeutic potential for the treatment of skin flap necrosis.