Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2016, Article ID 5782904, 11 pages
http://dx.doi.org/10.1155/2016/5782904
Research Article

A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies

1Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA
2Department of Cariology and Comprehensive Care, College of Dentistry, New York University, New York, NY 10010, USA
3Departments of Dermatology and Emergency Medicine, Stony Brook University, Stony Brook, NY 11794, USA
4Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA
5Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA

Received 16 December 2015; Revised 10 February 2016; Accepted 2 March 2016

Academic Editor: Toshiyasu Sasaoka

Copyright © 2016 Yazhou Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.