title: A Novel Chemically Modified Curcumin "Normalizes" Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies.
abstract: Introduction. Impaired wound-healing in diabetics can lead to life-threatening complications, such as limb amputation, associated in part with excessive matrix metalloproteinase- (MMP-) mediated degradation of collagen and other matrix constituents. In the current study, a novel triketonic chemically modified curcumin, CMC2.24, was tested for efficacy in healing of standardized skin wounds in streptozotocin-induced diabetic rats. Initially, CMC2.24 was daily applied topically at 1% or 3% concentrations or administered systemically (oral intubation; 30 mg/kg); controls received vehicle treatment only. Over 7 days, the diabetics exhibited impaired wound closure, assessed by gross and histologic measurements, compared to the nondiabetic controls. All drug treatments significantly improved wound closure with efficacy ratings as follows: 1% 2.24 > systemic 2.24 > 3% 2.24 with no effect on the severe hyperglycemia. In subsequent experiments, 1% CMC2.24 "normalized" wound-healing in the diabetics, whereas 1% curcumin was no more effective than 0.25% CMC2.24, and the latter remained 34% worse than normal. MMP-8 was increased 10-fold in the diabetic wounds and topically applied 1% (but not 0.25%) CMC2.24 significantly reduced this excessive collagenase-2; MMP-13/collagenase-3 did not show significant changes. Additional studies indicated efficacy of 1% CMC2.24 over more prolonged periods of time up to 30 days.
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of Cariology and Comprehensive Care, College of Dentistry, New York University, New York, NY 10010, USA.
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Dermatology and Emergency Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Steve A
authors.initials: SA
authors.lastname: McClain
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Hsi-Ming
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Muna S
authors.initials: MS
authors.lastname: Elburki
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cariology and Comprehensive Care, College of Dentistry, New York University, New York, NY 10010, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Wolff
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Johnson
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Lorne M
authors.initials: LM
authors.lastname: Golub
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: C000589611:1,7-bis(4-hydroxyphenyl)-4-N-phenylaminocarbonylhepta-1,6-dien-3,5-dione; D001786:Blood Glucose; D020784:Matrix Metalloproteinase 8; D003474:Curcumin