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.