Curcumin Affects the Progression of Diabetic Foot Ulcers by Regulating CRP Protein

Abstract

Background: Diabetic foot ulcer (DFU) is one of the major chronic complications of diabetes mellitus and is difficult to cure using existing conventional wound dressings. With the aim of finding more therapeutic targets for DFU, this study examined whether curcumin could improve DFU by altering the expression of C-reactive protein (CRP). Methods: DFU rat models were successfully constructed and treated with curcumin and different CRP mediators. The effect on DFU progression was then studied by evaluating the levels of fasting blood glucose (FBG) and serum CRP, the expression of CRP in wound tissue was detected by immunohistochemical (IHC) staining. The extent of granulation tissue formation and re-epithelialization was observed by Hematoxylin-Eosin (H&E) staining, the relative density of microvessels was detected by CD31 immunofluorescence staining, and collagen deposition and tissue fibrosis were observed by Masson staining. Results: The DFU animal model was successfully constructed and showed increased levels of FBG (p < 0.01) and serum CRP content (p < 0.01), and less wound healing (p < 0.001) on day 40. Treatment of DFU rats with 40 mg/kg curcumin (medium concentration) showed the best effect for the promotion of wound healing (p < 0.01), reducing the FBG level (p < 0.01), and reducing CRP (p < 0.01), with results even better than administration of sesame oil. Curcumin promoted the re-epithelialization of wound skin and new epidermis formation (p < 0.01), increased vascular density (p < 0.001), and increased collagen deposition (p < 0.01). These were all further improved by CRP knockdown (p < 0.05), and reversed by CRP overexpression (p < 0.01). Conclusion: Curcumin can affect the reconstruction of granulation tissue, angiogenesis, collagen formation and deposition, re-epithelialization and formation of tissue fibrosis in the damaged skin tissue of a rat model of DFU. It does this by reducing the expression of CRP, suggesting that curcumin and CRP may have clinical value in the treatment of DFU.