Molecular Changes in Diabetic Wound Healing following Administration of Vitamin D and Ginger Supplements: Biochemical and Molecular Experimental Study.

backgroundCirculating micro-RNAs are differentially expressed in various tissues and could be considered as potential regulatory biomarkers for T2DM and related complications, such as chronic wounds.

aimIn the current study, we investigated whether ginger extract enriched with [6]-gingerol-fractions either alone or in combination with vitamin D accelerates diabetic wound healing and explores underlying molecular changes in the expression of miRNA and their predicted role in diabetic wound healing.

methodsDiabetic wounded mice were treated with [6]-gingerol-fractions (GF) (25 mg/kg of body weight) either alone or in combination with vitamin D (100 ng/kg per day) for two weeks. Circulating miRNA profile, fibrogenesis markers, hydroxyproline (HPX), fibronectin (FN), and collagen deposition, diabetic control variables, FBS, HbA1c, C-peptide, and insulin, and wound closure rate and histomorphometric analyses were, respectively, measured at days 3, 6, 9, and 15 by RT-PCR and immunoassay analysis.

resultsTreatment of diabetic wounds with GF and vitamin D showed significant improvement in wound healing as measured by higher expression levels of HPX, FN, collagen, accelerated wound closure, complete epithelialization, and scar formation in short periods (11-13 days, (

conclusionTreatment with gingerols fractions (GF) and vitamin D for two weeks significantly improves delayed diabetic wound healing. The data showed that vitamin D and gingerol activate vascularization, fibrin deposition (HPX, FN, and collagen), and myofibroblasts in such manner to synthesize new tissues and help in the scar formation. Accordingly, three miRNAs, miR-155, miR-146a, and miR-15, as molecular targets, were identified and significantly evaluated in wound healing process. It showed significant association with fibrin deposition, vascularization, and reepithelialization process following treatment with GF and vitamin D. It proposed having anti-inflammatory action and promoting new tissue formation via vascularization process during the wound healing. Therefore, it is very interesting to consider miRNAs as molecular targets for evaluating the efficiency of nondrug therapy in the regulation of wound healing process.