Combined effect of substance P and curcumin on cutaneous wound healing in diabetic rats

Abstract Background Our earlier studies demonstrated that topically applied substance P (SP) or curcumin on excision skin wound accelerated the wound healing in streptozotocin-induced diabetic rats. In the present study, we aimed to evaluate the wound healing potential of combination of SP and curcumin in diabetic rats. Materials and methods Open cutaneous excision wound was created on the back of each of the 60 diabetic rats. Wound-inflicted rats were equally divided into three groups namely, control, gel treated, and SP + curcumin treated. Normal saline, pluronic gel, and SP (0.5 × 10−6 M) + curcumin (0.15%) were topically applied once daily for 19 d to these control, gel-treated, and SP + curcumin groups, respectively. Results SP + curcumin combination significantly accelerated wound closure and decreased messenger RNA expressions of tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9, whereas the combination markedly increased the expressions of interleukin-10, vascular endothelial growth factor, transforming growth factor-beta1, hypoxia-inducible factor 1-alpha, stromal cell–derived factors-1alpha, heme oxygenase-1 and endothelial nitric oxide synthase, and activities of superoxide dismutase, catalase, and glutathione peroxidase in granulation–healing tissue, compared with control and gel-treated groups. In combination group, granulation tissue was better, as was evidenced by improved fibroblast proliferation, collagen deposition, microvessel density, growth-associated protein 43–positive nerve fibers, and thick regenerated epithelial layer. Conclusions The combination of SP and curcumin accelerated wound healing in diabetic rats and both the drugs were compatible at the doses used in this study.