Scar tissue formation following skin wound healing is a challenging public health problem. Skin regeneration and preventing the formation of scar tissue by currently available commercial products are largely ineffective. This study aimed to test the efficacy of a novel topical metformin lotion (ML) in inhibiting scar tissue formation during skin wound healing in rats and to determine the mechanisms of action involved. A 6% ML was prepared in our laboratory. A skin wound healing model in rats was used. The wounded rats were divided into two groups and treated daily for 10 days as follows: Group 1 received a daily application of 50 mg of control lotion, or 0% ML (totaling 100 mg of lotion per rat), and Group 2 received a daily application of 50 mg of 6% ML (totaling 100 mg of 6% ML per rat). Blood samples from the heart of each rat were analyzed for inflammatory markers, HMGB1 and IL-1β, using ELISA, and immunological and histological analyses were performed on skin tissue sections. ML decreased levels of inflammatory markers HMGB1 and IL-1β in the serum of rats and inhibited the release of HMGB1 from cell nuclei into the skin tissue matrix. Additionally, ML demonstrated anti-fibrotic properties by enhancing AMPK activity, decreasing the expression of TGF-β1, reducing the number of myofibroblasts, decreasing the production of collagen III, and increasing the expression of collagen I. ML promotes the regeneration of high-quality skin during wound healing by reducing scar tissue formation. This effect is mediated through the activation of AMPK, inhibition of TGF-β1, and a decrease in the number of myofibroblasts.
Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.