Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing

J Nat Prod. 2013 Nov 22;76(11):2047-53. doi: 10.1021/np4002898. Epub 2013 Nov 7.

Abstract

Type 1 diabetes mellitus is responsible for metabolic dysfunction, accompanied by chronic inflammation, oxidative stress, and endothelium dysfunction, and is often associated with impaired wound healing. Phenol-rich food improves vascular function, contributing to diabetes prevention. This study has evaluated the effect of phenol-rich beverage consumption in diabetic rats on wound healing, through angiogenesis, inflammation, and oxidative stress modulation. A wound-healing assay was performed in streptozotocin-induced diabetic Wistar rats drinking water, 5% ethanol, and stout beer with and without 10 mg/L xanthohumol (1), for a five-week period. Wounded skin microvessel density was reduced to normal values upon consumption of 1 in diabetic rats, being accompanied by decreased serum VEGF-A and inflammatory markers (IL-1β, NO, N-acetylglucosaminidase). Systemic glutathione and kidney and liver H2O2, 3-nitrotyrosine, and protein carbonylation also decreased to healthy levels after treatment with 1, implying an improvement in oxidative stress status. These findings suggest that consumption of xanthohumol (1) by diabetic animals consistently decreases inflammation and oxidative stress, allowing neovascularization control and improving diabetic wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Glutathione / metabolism
  • Hydrogen Peroxide / metabolism
  • Inflammation / complications
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Liver / metabolism
  • Male
  • Neovascularization, Pathologic / metabolism
  • Oxidative Stress / drug effects*
  • Phenols / pharmacology
  • Propiophenones / chemistry
  • Propiophenones / pharmacology*
  • Rats
  • Rats, Wistar
  • Skin / drug effects
  • Tyrosine / analogs & derivatives
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects

Substances

  • Angiogenesis Inducing Agents
  • Flavonoids
  • Interleukin-1beta
  • Phenols
  • Propiophenones
  • Vascular Endothelial Growth Factor A
  • 3-nitrotyrosine
  • Tyrosine
  • Hydrogen Peroxide
  • Glutathione
  • xanthohumol