Timely repair of damaged skin is very important to maintain the integrity and homeostasis of skin, but the wound healing process is compromised in diabetic patients due to several extrinsic and intrinsic factors thus lead to leg
amputation and death eventually.
Sirtuins, a family of seven conserved
proteins are known to be associated with pathophysiological processes of the skin. The most important among them are sirt1and
sirt3 involved in cell regeneration and cell survival.
Naphthoquinone derivatives have a wide range of therapeutic properties, but the potential diabetic wound healing activity of
lapachol has not been identified yet. The present study thus aimed to investigate the wound healing effects of
lapachol in a diabetic mouse model. Diabetic wounded mice were divided into 3 groups; vehicle,
lapachol 0.05%, and
lapachol 0.1%. Skin samples collected from diabetic wounded mice on different time points
after treatment for 10 consecutive days were subjected to downstream analysis by western blot, ELISA and histology.
Lapachol treatment was found to enhance the expression of
sirt1/
sirt3 and other
proteins involved in cell migration and blood vessel formation. The tissue development rate was increased by
lapachol treatment with better
collagen deposition. Interestingly,
lapachol treatment also gave rise to a high concentration of
growth factors resulting in speedy and timely recovery of injured skin. In summary, our findings suggest that
lapachol promotes efficient wound healing in a diabetic mouse model by increasing the expression of
sirt1 and
sirt3 and other
proteins related to
wound repair and skin regeneration including α-PAK, RAC1/CDC42,
VEGF and
growth factors viz PDGF and
VEGF. This research work finds a novel potential activator of
sirtuins in the form of
lapachol and depicts the role of activated
sirtuins in diabetic wound healing.