Enhancing Wound Healing via Modulation of Autophagy-Induced Apoptosis: The Role of Nicotinamide Riboside and Resveratrol in Streptozotocin-Treated Diabetic Rat.

Background: Impaired wound healing from diabetes mellitus (DM) causes lower limb amputations, posing clinical, social, and economic issues. Hypoxia and advanced glycation end products cause autophagy and apoptosis dysregulation, which delays wound healing. The study will test systemic and topical Nicotinamide Riboside (NR) and Resveratrol (RSV) for the capacity to modulate autophagy and apoptosis via the SIRT-1-FOXO1 pathway and improve diabetic wound healing.

Methods: 54 male Sprague-Dawley rats were separated into control, diabetic (T1D), T1D-Gel-Base, T1D-NR, T1D-RSV, and T1D-NR+RSV groups. Rats were gavaged with 50 mg/kg/day RSV and 300 mg/kg/day NR for 5 weeks before having their wounds topically treated with 5% NR and RSV gel for 15 days after diabetes induction. Biochemical, histomorphometric, and stereological assays were conducted. The mRNA expressions of SIRT-1, FOXO1, VEGF, BAX, Cas3, Bcl-2, Beclin1, LC3IIβ, P62, and ATG5 were examined by qRT-PCR.

Results: NR and RSV improved diabetic rat wound closure. Diabetic rats treated with NR and RSV had significantly higher LC3IIβ, VEGEF, Bcl-2, and SIRT-1 mRNA levels. Bcl-2, p62, and ATG5 were regulated whereas BAX and Cas 3 were reduced. Stereological investigations showed epidermal, dermal, collagen bundle, vascular, and fibroblast density enhancements.

Conclusion: This study highlights the potential of NR and RSV, acting as SIRT-1 activators, in improving diabetic wound healing by regulating SIRT-1-FOXO1-mediated autophagy and apoptosis. These findings offer valuable insights for developing targeted strategies to enhance diabetic wound healing. The combination of NR and RSV showed promising effects, suggesting a potential therapeutic approach for improving diabetic wound healing.