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

• Published in: Journal of diabetes research 2016-01, Vol.2016 (2016), p.1-11
• Main Authors: Golub, Lorne M., Johnson, Francis, Zhang, Yu, Gu, Ying, Yu, Huiwen, Elburki, Muna S., Lee, Hsi-Ming, McClain, Steve A., Zhang, Yazhou, Wolff, Mark
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Administration, Oral; Animals; Binding sites; Blood Glucose - metabolism; Case-Control Studies; Collagen; Curcumin - analogs & derivatives; Curcumin - pharmacology; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - metabolism; Experiments; Hyperglycemia; Intubation; Life sciences; Male; Matrix Metalloproteinase 8 - drug effects; Matrix Metalloproteinase 8 - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Skin; Ulcers; Wound healing; Wound Healing - drug effects; Wounds and Injuries - metabolism
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2016/5782904

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.