Effect of Ellagic Acid on Wound Healing of Chronic Skin Ulceration in Diabetic Mice and Macrophage Phenotype Transformation

Abstract

Objection: To study the effect of modified formulae for ellagic acid (EA) on wound healing and macrophage phenotype transformation in diabetic mice. Materials and Methods: 10 db/m mice regarded as normal group, Dividing 20 db/db mice as the model group and EA group, 10 in every group. Surgical operation on the back was made to prepare experimental wound models. External medicines were applied and changed dressings every other day and measurement. Wound tissues were gained when animals were sacrificed by anesthesia 7 days later. Pathological changes were observed by HE and Masson staining methods, while using RT-PCR and IHC to measure mRNA and protein levels of MI/M2 type cytokines of the wound tissues. Results: Compared with the normal group, the wound area of db/db was greater (P < 0.001), while EA group less (P < 0.001). IL-12 and TNF-α mRNA and proteins levels in model group were higher (P < 0.001, respectively), while VEGF and TGF-βmRNA and proteins were lower. mRNA and protein levels of inflammato cytokines of EA group was all lower (P < 0.001), while the growth factor were significantly higher (P < 0.001). Conclusion: Wound healing of db/db mice was delayed and modified formulae for EA had effects on wound healing. The way by decreasing the Ml type inf1ammatory factors and improving the M2 type growth factors might be one of the mechanisms for wound healing.