Diabetes mellitus is a complex metabolic disease and delayed wound healing constitutes one of the most serious diabetes-associated complications. Diabetes can impede the wound healing process by inducing inflammation which can lead to delayed maturation of granulation tissues and reduced wound parallel tension. Brucine, one of the major constituents in Strychnos nux-vomica has antioxidant and anti-inflammatory properties. In this study, we investigated the effects of topical administration of brucine on the key mediators of wound healing, namely T cell subsets, glucocorticoid-induced tumor necrosis factor receptor expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, Th17 cells, Th1 cytokines, and inflammatory mediator mRNA expression.In current study, 5 groups of mice were used (10/group): group 1, the nondiabetic normal control; group 2, wound in nondiabetic mice; group 3, wound in diabetic mice; group 4, brucine 20mg/kg treated wounds in diabetic mice. Wound size was recorded on every third day and after 14 days of treatment, the heparinized whole blood and the wound tissue of all the groups was collected and tested. Brucine administration showed a significant reduction in wound size, the levels of GITR-expressing cells, and Th1 cytokines as well as substantial down regulation of mRNA expression of the inflammatory mediators compared with the diabetic mice. Brucine also significantly up regulated the number of Tregs or also induced Th17/Treg balance and modulated various pro-inflammatory and anti-inflammatory cytokines and the mRNA expression of their mediators. Furthermore, histopathological examination showed complete re-epithelization, decreased inflammatory cells and presence of granulation tissue in the brucine treated mice. Therefore, our results suggest the beneficial effect of brucine in enhanced wound healing and rebalancing the wound environment in diabetes.

Disclosure

H. Madkhali: None. M. Ganaie: None. M.N. Ansari: None.

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