Tryptanthrin promotes pressure ulcers healing in mice by inhibiting macrophage-mediated inflammation via cGAS/STING pathways

Pressure ulcers (PUs) is ischemic necrosis caused by long-term local tissue pressure, directly affecting postoperative functional recovery. There is evidence that inflammation has an adverse impact on the development of PUs and contributes to unfavorable outcomes, suggesting that blocking the inflammatory response may be a promising therapeutic strategy for PUs. Tryptanthrin (Tryp), a natural product isolated from indigenous plants, has an anti-inflammatory biological function. However, the efficacy of Tryp in PUs remains unclear. Efficacy of Tryp suppressed inflammation was assessed using magnets-induced PUs model in mice. Hematoxylin-Eosin staining, masson staining and immunohistochemistry were used to evaluate the histologic changes after the formation of PUs. The expression of inflammatory cytokines was detected by qRT-PCR. And we detected the expression of protein by Western blotting. Tryp could promote wound healing, such as epidermal thickening, revascularization, and nerve regeneration. Then the treatment of Tryp was able to promote fibroblast migration and collagen deposition. Moreover, Tryp attenuated inflammation through inducing macrophage polarization to M2 phenotype by suppressing the activation of cGAS-STING pathway. Tryp could reduce the release of inflammatory cytokines, and induce RAW 264.7 polarization to M2 phenotype by targeting cGAS/STING/TBK1 pathways. In summary, Tryp may be a novel medicine for the treatment of PUs in the future.