Selenium added unripe carica papaya pulp extracts enhance wound repair through TGF-β1 and VEGF-a signalling pathway

BMC Complement Altern Med. 2015 Oct 15:15:369. doi: 10.1186/s12906-015-0900-4.

Abstract

Background: Increased wound healing efficiency by Se(2+) added Carica papaya L. (Caricaceae) fruit extract was linked to increased antioxidant and anti-inflammatory responses during healing. We investigated the impact of Se(2+) or Zn(2+) added papaya water (WE) and phosphate-buffered saline (PE) extracts on cells recruitment and bio-molecular alterations on days 4 and 10 post wounding in an in vivo excision wound.

Methods: Excision wounds were created on the dorsum of Sprague Dawley rats and treated topically twice/day with 20 μL of PE and WE (5 mg extract/mL), 0.5 μgSe(2+) added PE and WE (PES and WES), or 100 μMZn(2+) added PE and WE (PEZ and WEZ). Deionised water (negative) and Solcoseryl (positive) were applied on the control groups. Histochemical and biochemical assays were used to evaluate cellular and bio-molecular changes in the wound.

Results: PES (PE + 0.5 μg Se(2+)) only increased significantly (p < 0.05) wound total protein content (95.14 ± 1.15 mg/g tissue vs positive control; 80.42 ± 0.86 mg/g tissue) on day 10 post wounding. PES increased significantly (p < 0.05) the number of fibroblasts/high power field (HPF) (75.60 ± 9.66) but decreased significantly (p < 0.05) the number of polymorphonuclear leukocytes/HPF (59.20 ± 12.64) in the wound compared to positive control (50.60 ± 12.58 fibroblasts/HPF, 101.00 ± 27.99 polymorphonuclear leukocytes/HPF) on day 4. Similar results were recorded for WES. PES demonstrated increased neovascularization, TGF-β1 and VEGFA expressions at day 4 and increased collagen at day 10.

Conclusion: Papaya extract improved wound repair by increasing fibroblasts recruitment and reducing polymorphonuclear leukocytes infiltration through early transient expressions of TGF-β1 and VEGFA at the wound area. The processes were amplified with Se(2+) addition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carica / chemistry*
  • Collagen / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fruit / chemistry
  • Humans
  • Male
  • Plant Extracts / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Selenium / pharmacology*
  • Signal Transduction* / drug effects
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Wound Healing / drug effects*
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / genetics
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / physiopathology

Substances

  • Plant Extracts
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • Collagen
  • Selenium