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...
Saved in:
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2016-01-01
|
Series: | Journal of Diabetes Research |
Online Access: | http://dx.doi.org/10.1155/2016/5782904 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832549404369747968 |
---|---|
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. |
format | Article |
id | doaj-art-c58afdf337fa4e6da869671d2f783c14 |
institution | Kabale University |
issn | 2314-6745 2314-6753 |
language | English |
publishDate | 2016-01-01 |
publisher | Wiley |
record_format | Article |
series | Journal of Diabetes Research |
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 |
work_keys_str_mv | AT yazhouzhang anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT steveamcclain anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT hsiminglee anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT munaselburki anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT huiwenyu anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT yinggu anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT yuzhang anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT markwolff anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT francisjohnson anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT lornemgolub anovelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT yazhouzhang novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT steveamcclain novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT hsiminglee novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT munaselburki novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT huiwenyu novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT yinggu novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT yuzhang novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT markwolff novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT francisjohnson novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies AT lornemgolub novelchemicallymodifiedcurcuminnormalizeswoundhealinginratswithexperimentallyinducedtypeidiabetesinitialstudies |