Curcumin-induced angiogenesis hastens wound healing in diabetic rats

J Surg Res. 2015 Feb;193(2):978-88. doi: 10.1016/j.jss.2014.10.019. Epub 2014 Oct 18.

Abstract

Background: Neovasculogenesis, vital for wound healing, gets compromised in diabetics patients, which consequently delayed wound healing. Previous studies have shown curcumin as both a stimulatory and an inhibitory agent in the neovasculogenesis process. So, present study was aimed to investigate the effects of curcumin on wound healing in diabetic rats and to explore the expressions of the various factors involved in neovasculogenesis.

Materials and methods: Open excisional diabetic wound was created in sixty rats and divided into three groups viz. i) control, ii) pluronic gel-treated, and iii) curcumin-treated. The pluronic F-127 gel (25%) and curcumin (0.3%) in the pluronic gel were topically applied once daily for 19 d. The wound healing and neovasculogenesis among these groups were evaluated by gross appearance of wounds and microscopically by hematoxylin and eosin staining, immunohistochemistry for CD31, messenger RNA expressions of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, hypoxia-inducible growth factor-1 alpha, stromal cell-derived growth factor-1 alpha, and heme oxygenase-1, and Western blotting studies of VEGF and TGF-β1 in granulation and/or healing tissue on days 3, 7, 14, and 19.

Results: Curcumin application caused markedly fast wound closure with well-formed granulation tissue dominated by fibroblast proliferation, collagen deposition, and complete early regenerated epithelial layer. Immunohistochemistry for CD31 revealed well-formed blood vessels with increased microvessel density on days 3, 7, and 14 in the curcumin-treated group. Expressions of VEGF and TGF-β1 on days 3, 7, and 14, hypoxia-inducible growth factor-1 alpha, stromal cell-derived growth factor-1 alpha, and heme oxygenase-1 on days 3 and 7 were increased in curcumin-treated diabetic rats, as compared with other groups.

Conclusions: Curcumin enhanced the neovasculogenesis and accelerated the wound healing in diabetic rats by increased expressions of various factors.

Keywords: Curcumin; Diabetic wound; Healing; Neovasculogenesis; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Chemokine CXCL12 / metabolism
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Diabetes Mellitus, Experimental / complications*
  • Drug Evaluation, Preclinical
  • Heme Oxygenase (Decyclizing) / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Neovascularization, Physiologic / drug effects*
  • Nitric Oxide Synthase Type III / metabolism
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats, Wistar
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*

Substances

  • Antineoplastic Agents
  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Plant Extracts
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Curcumin