title: Topical application of the bee hive protectant propolis is well tolerated and improves human diabetic foot ulcer healing in a prospective feasibility study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Frances R
authors.initials: FR
authors.lastname: Henshaw
authors.affiliation: Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Thyra
authors.initials: T
authors.lastname: Bolton
authors.affiliation: Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nube
authors.affiliation: Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Anita
authors.initials: A
authors.lastname: Hood
authors.affiliation: Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Danielle
authors.initials: D
authors.lastname: Veldhoen
authors.affiliation: Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Pfrunder
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Department of Microbiology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Genevieve L
authors.initials: GL
authors.lastname: McKew
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Department of Microbiology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Colin
authors.initials: C
authors.lastname: Macleod
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Susan V
authors.initials: SV
authors.lastname: McLennan
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Diabetes Centre, Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia. Electronic address: stephen.twigg@sydney.edu.au.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Twigg
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000009:adverse effects; D058491:Bacterial Load / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism / Q000382:microbiology; D017719:Diabetic Foot / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D011429:Propolis / Q000008:administration & dosage* / Q000009:adverse effects; D020011:Protective Agents / Q000008:administration & dosage / Q000009:adverse effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D020011:Protective Agents; D011429:Propolis; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Bacteria; Diabetic foot ulcer; MMP-9; Pilot; Propolis