Elsevier

Burns

Volume 48, Issue 6, September 2022, Pages 1452-1461
Burns

Topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway

https://doi.org/10.1016/j.burns.2021.10.019Get rights and content
Under a Creative Commons license
open access

Highlights

  • Pterostilbene (PTE) completely, while RSV partly, reverses hyperglycemia-induced oxidative stress.

  • PTE significantly reverses hyperglycemia-induced suppression of HIF1α signaling pathway.

  • Topical administration of PTE diminishes diabetes-induced oxidative stress and HIF1α suppression.

  • Topical administration of PTE accelerates burn wound healing in diabetes.

  • PTE may provide a potential therapeutic strategy for burn wound healing in diabetes.

Abstract

Impaired wound healing is one of a variety of severe diabetic complications and involves many factors, including consistent oxidative stress, prolonged inflammation, impaired angiogenesis, and delayed re-epithelialization. Despite the severe negative impacts that impaired wound healing has on patients’ lives, detailed mechanisms and effective therapies are still not fully developed. In this study, we aim to investigate the potential effects and mechanisms of topical administration of pterostilbene and resveratrol on burn wound healing in diabetes. Our in vitro experiments in human umbilical vein endothelial cells showed that long term exposure of hyperglycemia induces oxidative stress and suppression of hypoxia inducible factor1α (HIF1α) signaling pathway, and pterostilbene treatment completely, while resveratrol treatment partly, reversed this effect. Further in vivo experiments in diabetic rats showed that topical administration of pterostilbene exhibited stronger efficacy than resveratrol in normalizing oxidative stress, HIF1α activity, and accelerating burn wound healing in diabetes. We conclude that topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway; thus, pterostilbene may be a potential candidate for clinical treatment of burn wound healing in diabetes.

Abbreviations

ARNT
aryl hydrocarbon receptor nuclear translocator
ChIP
chromatin immunoprecipitation
ERβ
estrogen receptor β
HIF1α
hypoxia-inducible factor-1α
HUVEC
Human Umbilical Vein Endothelial Cells
O2.-
superoxide anion
MG
Methylglyoxal
8-OHdG
8-hydroxy-2′-deoxyguanosine
PTE
pterostilbene
ROS
reactive oxygen species
RSV
resveratrol
STZ
streptozotocin
VEGF
vascular endothelial growth factor

Keywords

Diabetes
HIF1α
Oxidative stress
Pterostilbene
Burn wound healing

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1

These authors contributed to this manuscript equally.