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: Yazhou Zhang, Steve A McClain, Hsi-Ming Lee, Muna S Elburki, Huiwen Yu, Ying Gu, Yu Zhang, Mark Wolff, Francis Johnson, Lorne M Golub
• Journal: Journal of diabetes research (J Diabetes Res) Vol. 2016 Pg. 5782904 ( 2016) ISSN: 2314-6753 [Electronic] England
• PMID: 27190999 (Publication Type: Journal Article)

Chemical References

• 1,7-bis(4-hydroxyphenyl)-4-N-phenylaminocarbonylhepta-1,6-dien-3,5-dione
• Blood Glucose
• Matrix Metalloproteinase 8
• Curcumin

Topics

• Administration, Cutaneous
• Administration, Oral
• Animals
• Blood Glucose (metabolism)
• Case-Control Studies
• Curcumin (analogs & derivatives, pharmacology)
• Diabetes Mellitus, Experimental (metabolism)
• Diabetes Mellitus, Type 1 (metabolism)
• Male
• Matrix Metalloproteinase 8 (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Wound Healing (drug effects)
• Wounds and Injuries (metabolism)