Ginsenoside Rb3 attenuates skin flap ischemia-reperfusion damage by inhibiting STING-IRF3 signaling

J Mol Histol. 2022 Aug;53(4):763-772. doi: 10.1007/s10735-022-10081-x. Epub 2022 Jun 22.

Abstract

We investigate the protective effect of ginsenoside Rb3 on skin flap microvasculature following ischemia-reperfusion (I/R) injury and its regulatory mechanism. We used a rat model of I/R injury with the right iliolumbar artery and oxidative stress model of human dermal microvascular endothelial cells. The effects of Rb3 on skin flap tissue and endothelial cell survival, STING-IRF3 pathway activation, and endothelial cell adhesion were measured. Following reperfusion, the survival rate of rat perforator flaps in the Rb3-treated group gradually increased with increasing Rb3 concentration. The treatment also reduced the amount of STING protein, phosphorylated IRF3, and P-selectin in skin flap tissue, with this change being most obvious in microvascular endothelial cells. In vitro, activated IRF3 binds to the P-selectin promoter and induces P-selectin expression. Our results suggest that Rb3 plays a role in reducing I/R flap damage through negatively regulating STING-IRF3 activation to limit leukocyte-endothelial cell adhesion.

Keywords: Endothelial activation; Ginsenoside Rb3; Microcirculation disorders; P-selectin; STING-IRF3 pathway; Skin flap transplantation.

MeSH terms

  • Animals
  • Endothelial Cells
  • Ginsenosides
  • Humans
  • Interferon Regulatory Factor-3
  • Ischemia
  • P-Selectin*
  • Rats
  • Reperfusion Injury* / drug therapy

Substances

  • Ginsenosides
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • P-Selectin
  • ginsenoside Rb3