1529 A Novel Chemically-Modified Curcumin (CMC2.24) Improves Diabetic Wound-Healing

Saturday, March 24, 2012: 9:45 a.m. - 11 a.m.
Presentation Type: Poster Session
H.W. YU1, Y. ZHANG1, Y. ZHANG2, H. LEE3, S.A. MCCLAIN4, F. JOHNSON2, and L.M. GOLUB5, 1State University of New York - Stony Brook, Stony Brook, NY, 2Department of Chemistry, State University of New York - Stony Brook, Stony Brook, NY, 3Oral Biology and Pathology, State University of New York - SUNY - Stony Brook, Stony Brook, NY, 4Departments of Dermatology and Emergency Medicine, State University of New York - Stony Brook, Smithtown, NY, 5School of Dental Medicine, State University of New York - SUNY - Stony Brook, Stony Brook, NY
Objective: To identify a curcumin-derived potent MMP inhibitor and investigate its effectiveness to enhance wound-healing in a diabetic rat model. 

Method: A congener series of five chemically-modified curcumins were assessed in vitro by a fluorogenic substrate assay for their ability to inhibit matrix metalloproteinases. The most potent of these, CMC2.24 was selected for in vivo wound-healing studies in a streptozotocin-induced diabetic rat model, using the dorsal skin defect method (six wounds of 6mm diam. symmetrically located on each rat). Fifteen male Sprague-Dawley rats were distributed into five groups (n=3/group). Group I: non-diabetic healthy rats (control); Group II: diabetic but received no CMC; Groups III and IV: diabetic and their wounds were treated topically with either 1% or 3% of CMC2.24, once daily for seven days (all groups received vehicles daily). Group V: diabetic treated with CMC 2.24 by oral gavage. At sacrifice, granulation tissues, and blood were collected for analysis of MMP-9 activity and glucose content (histology will be discussed elsewhere).

Result: Of the five CMC compounds tested in vitro, CMC2.24 showed the most favorable IC50 against MMP-9 and MMP-13. In vivo topical administration of 1% CMC2.24, to a lesser extent 3% CMC2.24, improved clinically-measured wound healing (p<0.05) and reduced the pathologically-excessive MMP-9 levels in diabetic wounds compared to vehicle-alone (p<0.001). Interestingly the topical treatments had no effect, neither on the levels of the constitutive MMP-2 nor on the severity of the hyperglycemia. 


Conclusion: In the in vitro study we identified a potent but selective MMP inhibitor, namely CMC2.24. The compound significantly improved wound healing and attenuated inflammation-induced MMP-9 in the skin of the wounds of diabetic rats. CMC 2.24 therefore has a demonstrated therapeutic potential to resolve inflammation during the healing of diabetic wounds and other inflammatory responses associated with the presence of excessive levels of MMPs.

This abstract is based on research that was funded entirely or partially by an outside source: NYSTAR grant # A43273 from the Center for Advanced Technology (SBU), Chem-Master Int. Inc. and the SBU Summer Research Fellowship Program

Keywords: Wound healing