ABSTRACT
AIMS: Propolis is a naturally occurring anti-inflammatory bee derived protectant resin. We have previously reported that topically applied propolis reduces inflammation and improves cutaneous ulcer healing in diabetic rodents. The aim of this study was to determine if propolis shows efficacy in a pilot study of human diabetic foot ulcer (DFU) healing and if it is well tolerated. MATERIALS: Serial consenting subjects (n=24) with DFU ≥4 weeks' duration had topical propolis applied at each clinic review for 6 weeks. Post-debridement wound fluid was analyzed for viable bacterial count and pro-inflammatory MMP-9 activity. Ulcer healing data were compared with a matched control cohort of n=84 with comparable DFU treated recently at the same center. RESULTS: Ulcer area was reduced by a mean 41% in the propolis group compared with 16% in the control group at week 1 (P<0.001), and by 63 vs. 44% at week 3, respectively (P<0.05). In addition, 10 vs. 2% (P<0.001), then 19 vs. 12% (P<0.05) of propolis treated vs. control ulcers had fully healed by weeks 3 and 7, respectively. Post-debridement wound fluid active MMP-9 was significantly reduced, by 18.1 vs. 2.8% week 3 from baseline in propolis treated ulcers vs. controls (P<0.001), as were bacterial counts (P<0.001). No adverse effects from propolis were reported. CONCLUSIONS: Topical propolis is a well-tolerated therapy for wound healing and this pilot in human DFU indicates for the first time that it may enhance wound closure in this setting when applied weekly. A multi-site randomized controlled of topical propolis now appears to be warranted in diabetic foot ulcers.
Subject(s)
Anti-Infective Agents, Local/administration & dosage , Diabetic Foot/drug therapy , Propolis/administration & dosage , Wound Healing/drug effects , Administration, Topical , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Infective Agents, Local/adverse effects , Bacterial Load/drug effects , Body Fluids/metabolism , Body Fluids/microbiology , Diabetic Foot/microbiology , Diabetic Foot/physiopathology , Feasibility Studies , Female , Humans , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Middle Aged , Propolis/adverse effects , Protective Agents/administration & dosage , Protective Agents/adverse effectsABSTRACT
OBJECTIVE: We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-beta1 (TGF-beta1) with wound healing rate. RESEARCH DESIGN AND METHODS: The ulcers were cleansed to remove exudates, and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1, and TGF-beta1. RESULTS: At presentation, MMP-9 and the MMP-9-to-TIMP-1 ratio correlated inversely with the wound healing rate at 28 days (P < 0.001). MMP-9 and the MMP-9-to-TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 who did not. The pro-MMP-9 concentration was predictive of healing within 12 weeks. Addition of cutoffs for TIMP-1 (>480 pg/ml) and TGF-beta (>115 pg/ml) further improved its predictive power (area under the curve 0.94). CONCLUSIONS: These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1, and TGF-beta in wound fluid may help to identify ulcers at risk of poor healing.
