title: Selenium added unripe carica papaya pulp extracts enhance wound repair through TGF-β1 and VEGF-a signalling pathway.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Science, International Islamic University Malaysia, Bandar Indera Mahkota, Kuantan, 25200, Pahang, Malaysia.
authors.forename: Abdulrazaq Bidemi
authors.initials: AB
authors.lastname: Nafiu
authors.affiliation: Faculty of Dentistry, University Malaya, Kuala Lumpur, 50603, Malaysia. m.tariqur.rahman@gmail.com.
authors.forename: Mohammad Tariqur
authors.initials: MT
authors.lastname: Rahman
mesh_terms: D000818:Animals; D029441:Carica / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005638:Fruit / Q000737:chemistry; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D010936:Plant Extracts; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D012643:Selenium