Resveratrol accelerates wound healing by inducing M2 macrophage polarisation in diabetic mice

Pharm Biol. 2022 Dec;60(1):2328-2337. doi: 10.1080/13880209.2022.2149821.

Abstract

Context: The reduction in M2 macrophage polarisation plays a major role during diabetic wound healing. Resveratrol (RSV) can promote the polarisation of M2 macrophages and accelerate diabetic wound healing. However, the specific mechanism by which RSV regulates M2 macrophage polarisation to promote diabetic wound healing is unclear.

Objective: This study evaluated the effectiveness of RSV on diabetic wound healing and analysed the underlying mechanisms.

Materials and methods: STZ-induced C57/B6 mice were used as a diabetic mice model for a period of 15 days. RSV (10 μmol/L) was injected around the wound to evaluate the effect of RSV on the healing process of diabetic wounds. The human monocyte line THP-1 was used to evaluate the effects of RSV (10 μmol/L) on polarisation of M2 macrophages and the secretion of pro-inflammatory factors.

Results: In vivo, RSV significantly increased diabetic wound healing (p < 0.05) and make the regenerated skin structure more complete. And it promoted the expression of α-SMA and Collagen I (p < 0.05). Moreover, RSV reduced the secretion of inflammatory factors (TNF-α, iNOS and IL-1β) (p < 0.05) and promoted M2 macrophage polarisation by increasing Arg-1 and CD206 expression (p < 0.01). In vitro, RSV promoted the polarisation of M2 macrophages (p < 0.001) and reduced the secretion of pro-inflammatory factors (TNF-α, IL-6 and IL-1β) (p < 0.05). The therapeutic effects of RSV were all significantly reversed with LY294002 (p < 0.01).

Discussion and conclusions: RSV has the positive effects on promoting the acceleration and quality of skin wound healing, which provides a scientific basis for clinical treatment in diabetic wound.

Keywords: Diabetic wounds; PI3K/Akt; STZ; THP-1; inflammation.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Humans
  • Macrophages
  • Mice
  • Resveratrol / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Wound Healing

Substances

  • Resveratrol
  • Tumor Necrosis Factor-alpha

Grants and funding

All authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China [NO. 81671922, 81974288].