Abstract:
One of the complications of diabetes is a delay in the healing of wounds, which, if not
treated timely, might result in the amputation of lower limbs. Sirtuins have significant
functions in regulating a wide range of biological processes, including metabolic diseases
and inflammation. Sirtuins 1, 3, and 6 are promising therapeutic targets in treating diabetic
wounds. However, the target genes of these situations and their effects on gene expression
are yet to be fully understood in diabetic wound healing. This study used lapachol to
increase sirtuin levels in diabetic mice. Lapachol is a naphthoquinone and exhibits a broad
range of therapeutics. In the in-vivo experiment, a wound was created in diabetic mice, and
lapachol was applied topically on the mice skin. Wound contraction was monitored from
days 1 to 10. Mice treated with 0.1% lapachol showed the most accelerated wound closure
compared to other groups, signifying lapachol healing capability. An in-silico analysis was
conducted to find key gene targets of the activated sirtuins involved in diabetic wound
healing, and several functional studies were performed using tools and databases such as
ShinyGO, Ingenuity Pathway Analysis and Kyoto Encyclopedia of Genes Genomes
pathway (KEGG), and Cytoscape analysis. XRCC6, FOXO3, HIF1A, P53, NNT,
PPARGC1A, PPARγ, PPARα, and GLUT1 are potential key gene targets of activated
sirtuin 1, 3, and 6, which are probably involved in diabetic wound regulation. This can
offer therapeutic potential for improving the healing of diabetic wounds.
