Resveratrol Promotes Diabetic Wound Healing by Inhibiting Notch Pathway

J Surg Res. 2024 May:297:63-70. doi: 10.1016/j.jss.2024.02.004. Epub 2024 Mar 5.

Abstract

Introduction: Diabetic foot ulcer (DFU) is a severe complication that threatens the daily lives of patients with diabetes and represents a serious challenge to the global health system. Considering that impaired wound healing is the leading cause of DFU, exploring the mechanism of diabetic wound healing is beneficial for improving DFU treatment. Resveratrol (RES) is a native polyphenol with various pharmacological characteristics, and recent studies have indicated an accelerated function of RES in diabetic wound healing. As human dermal fibroblasts (HDFs) play a significant role in diabetic wound healing, this study aimed to elucidate the regulatory mechanism of RES in HDFs.

Methods: To mimic diabetic wound healing in vitro, the HDFs were stimulated with high glucose (HG). Our findings revealed that RES reversed HG-induced suppression of HDF proliferation and migration caused by HG. RES inhibits the Notch signaling pathway. More importantly, we demonstrated that the activation of the Notch pathway abrogated the effects of RES on HG-induced HDFs.

Results: In vivo assays also illustrated that RES contributed to wound healing in diabetic mice by blocking the Notch pathway.

Conclusions: In conclusion, RES improved diabetic wound healing by targeting the Notch pathway, which offers novel insights into DFU therapy.

Keywords: Diabetic wound healing; Human dermal fibroblast; Notch pathway; Resveratrol.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Foot*
  • Humans
  • Mice
  • Resveratrol / pharmacology
  • Skin / metabolism
  • Wound Healing

Substances

  • Resveratrol