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

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 chemicall...

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Main 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
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2016/5782904
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author Yazhou Zhang
Steve A. McClain
Hsi-Ming Lee
Muna S. Elburki
Huiwen Yu
Ying Gu
Yu Zhang
Mark Wolff
Francis Johnson
Lorne M. Golub
author_facet Yazhou Zhang
Steve A. McClain
Hsi-Ming Lee
Muna S. Elburki
Huiwen Yu
Ying Gu
Yu Zhang
Mark Wolff
Francis Johnson
Lorne M. Golub
author_sort Yazhou Zhang
collection DOAJ
description 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.
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spelling doaj-art-c58afdf337fa4e6da869671d2f783c142025-02-03T06:11:22ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/57829045782904A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial StudiesYazhou Zhang0Steve A. McClain1Hsi-Ming Lee2Muna S. Elburki3Huiwen Yu4Ying Gu5Yu Zhang6Mark Wolff7Francis Johnson8Lorne M. Golub9Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartments of Dermatology and Emergency Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USADepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USADepartment of Cariology and Comprehensive Care, College of Dentistry, New York University, New York, NY 10010, USADepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USADepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USAIntroduction. 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.http://dx.doi.org/10.1155/2016/5782904
spellingShingle Yazhou Zhang
Steve A. McClain
Hsi-Ming Lee
Muna S. Elburki
Huiwen Yu
Ying Gu
Yu Zhang
Mark Wolff
Francis Johnson
Lorne M. Golub
A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies
Journal of Diabetes Research
title A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies
title_full A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies
title_fullStr A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies
title_full_unstemmed A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies
title_short A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies
title_sort novel chemically modified curcumin normalizes wound healing in rats with experimentally induced type i diabetes initial studies
url http://dx.doi.org/10.1155/2016/5782904
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