Natural SIRT1 modifiers as promising therapeutic agents for improving diabetic wound healing

Background: The occurrence of chronic wounds, account for significant suffering of diabetic people, together with increasing healthcare burden. The chronic wounds associated with diabetes do not undergo the normal healing process rather stagnate into chronic proinflammatory phase as well as declined fibroblast function and impaired cell migration.

Hypothesis: SIRT1, which is the most studied isoform of the sirtuin family in mammals, has now emerged as a crucial target for improving diabetic wound healing. It is an NAD⁺ dependent deacetylase, originally characterized to deacetylate histone proteins leading to heterochromatin formation and gene silencing. It is now known to regulate a number of cellular processes like cell proliferation, division, senescence, apoptosis, DNA repair, and metabolism.

Methodology: The retrieval of potentially relevant studies was done by systematically searching of three databases (Google Scholar, Web of science and PubMed) in December 2019. The keywords used as search terms were related to SIRT1 and wound healing. The systematic search retrieved 649 papers that were potentially relevant and after selection procedure, 73 studies were included this review and discussed below.

Results: Many SIRT1 activating compounds (SACs) were found protective and improve diabetic wound healing through regulation of inflammation, cell migration, oxidative stress response and formation of granulation tissue at the wound site.

Conclusions: However, contradictory reports describe the opposing role of SACs on the regulation of cell migration and cancer incidence. SACs are therefore subjected to intense research for understanding the mechanisms responsible for controlling cell migration and therefore possess prospective to enter the clinical arena in the foreseeable future.

Keywords: Adiponectin; Bergenin; Diabetes; Sirtuin activating compounds; Sirtuins; Wound healing.