Abstrato

By promoting the expression, resveratrol improves wound healing in type 1 diabetes mellitus

Ashish Pati

Diabetic non-healing skin ulcers provide a significant clinical issue, and the disruption of angiogenesis and endothelial dysfunction brought on by hyperglycemia is a key factor. Resveratrol (RES), a Silent Information Regulator 1 (SIRT1) agonist, has become a research focus for the treatment of diabetic non-healing skin ulcers; however, the underlying mechanism by which RES regulates these processes is still unknown. RES can improve endothelial function and has strong pro-angiogenic properties. The goal of the current investigation was to ascertain whether RES alleviates hyperglycemia-induced endothelial dysfunction and the disruption of angiogenesis in order to exercise its apparent protective role in diabetic wound healing. By using semi-quantitative RT-PCR, western blot analysis, terminal deoxynucleotidyl transferasemediated dUTP nick end labelling (TUNEL) staining, and immunofluorescence in vitro on 33 mM high glucose-stimulated Human Umbilical Vein Endothelial Cells (HUVECs), we examined the effects of RES on cell migration, cell proliferation, apoptosis, tube formation By using TUNEL labelling, immunofluorescence, and in vivo photography, we looked into the impact of RES on endothelial dysfunction and wound healing disruption in db/db mice in more detail. We noticed a clear reduction of the angiogenesis and endothelial dysfunction that hyperglycemia causes, which was followed by the stimulation of diabetic wound healing via RES and the activation of the SIRT1 signalling pathway that had been hindered by hyperglycemia. Diabetic wound healing was delayed after pretreatment with the SIRT1 inhibitor EX-527 eliminated the RESmediated endothelial protection and pro-angiogenesis effect. RES activated SIRT1 to restore hyperglycemia-triggered endothelial dysfunction and disturbance of angiogenesis, followed by the promotion of diabetic wound healing in a c-Myc-dependent manner, according to further research into the overexpression of fork head box O1 (FOXO1), a transcription factor substrate of SIRT1. Pretreatment with the c-Myc inhibitor 10058-F4 inhibited the angiogenesis, endothelial protection, and diabetic wound healing that is mediated by RES. Our results suggest that the suppression of FOXO1 and the de-repression of c-Myc expression are necessary for RES to play a beneficial role in diabetic wound healing via its SIRT1-dependent endothelial protection and pro-angiogenic actions.