title: Improved function of diabetic wound-site macrophages and accelerated wound closure in response to oral supplementation of a fermented papaya preparation.
abstract: 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.
authors.affiliation: Comprehensive Wound Center, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Collard
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D001769:Blood / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D029441:Carica; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics; D019587:Dietary Supplements; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005285:Fermentation; D005638:Fruit / Q000382:microbiology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D028321:Plant Preparations / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D008070:Lipopolysaccharides; D008074:Lipoproteins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D028321:Plant Preparations; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D042461:Vascular Endothelial Growth Factor A; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C467480:vascular endothelial growth factor A, mouse; C496317:Nos2 protein, mouse