Improved function of diabetic wound-site macrophages and accelerated wound closure in response to oral supplementation of a fermented papaya preparation

Antioxid Redox Signal. 2010 Sep 1;13(5):599-606. doi: 10.1089/ars.2009.3039.


Carica papaya Linn is widely known as a medicinal fruit. We sought to study a standardized fermented papaya preparation (FPP) for its effects on wound healing in adult obese diabetic (db/db) mice. FPP blunted the gain in blood glucose and improved the lipid profile after 8 weeks of oral supplementation. However, FPP did not influence weight gain during the supplementation period. FPP (0.2 g/kg body weight) supplementation for 8 weeks before wounding was effective in correcting wound closure. Studies on viable macrophages isolated from the wound site demonstrated that FPP supplementation improved respiratory-burst function as well as inducible NO production. Reactive oxygen species support numerous aspects of wound healing; NO availability in diabetic wounds is known to be compromised. Diabetic mice supplemented with FPP showed a higher abundance of CD68 as well as CD31 at the wound site, suggesting effective recruitment of monocytes and an improved proangiogenic response. This work provides the first evidence that diabetic-wound outcomes may benefit from FPP supplementation by specifically influencing the response of wound-site macrophages and the subsequent angiogenic response. Given that FPP has a long track record of safe human consumption, testing of the beneficial effects of FPP on diabetic wound-related outcomes in a clinical setting is warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Blood / drug effects
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Carica*
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology
  • Diabetes Complications / therapy*
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / genetics
  • Dietary Supplements
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fermentation*
  • Fruit / microbiology*
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Insulin / blood
  • Lipids / blood
  • Lipopolysaccharides / pharmacology
  • Lipoproteins / blood
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Obese
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Plant Preparations / administration & dosage*
  • Plant Preparations / pharmacology
  • Plant Preparations / therapeutic use*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Vascular Endothelial Growth Factor A / genetics
  • Wound Healing / drug effects*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology
  • Wounds and Injuries / therapy


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Blood Glucose
  • CD68 protein, mouse
  • Insulin
  • Lipids
  • Lipopolysaccharides
  • Lipoproteins
  • Plant Preparations
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Reactive Oxygen Species
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Superoxides
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Tetradecanoylphorbol Acetate