Sinapic Acid Attenuates Hypertrophic Scarring by Modulating the TGF‐β1/Smad Pathway: An In Vivo and In Vitro Investigation

Rationale Hypertrophic scars are formed as a result of excess collagen and fibroblast activity during the tissue healing process and can result in loss of function. Sinapic acid (SA) is a naturally occurring phenolic compound with antifibrotic, anti‐inflammatory, and antioxidant properties. Aims and Objectives This study aims to evaluate the ability of SA to inhibit hypertrophic scar generation and explain the mechanisms through which this happens by performing both in vivo and in vitro experiments. Methods A rat tail wound model in vivo was employed to assess the impact of SA on the pathological scar area, biomolecule deposition, and fibroblast multiplication. Histopathological, immunohistochemistry, and molecular tests were also performed. Fibroblast cell culture of hypertrophic scar fibroblast cells was used in addition to SA treatment to measure cell growth, movement activity, cell division phases, and fibrotic‐related proteins. Results In vivo results showed that SA reduced the area of scarring in skin tissues and enhanced the organization of collagen, with the high‐concentration group showing the most improvement. The reduction in TGF‐β1 and P‐SMAD2 was established through immunohistochemistry assays. In vitro findings indicated SA to decrease cell proliferation and movement capabilities of fibroblasts, as well as blocking the G1 phase and resulting in apoptosis. SA also downregulated key fibrosis markers including COL1A1, COL3A1, and α‐SMA. Conclusions Modulation of the TGF‐β1/Smad pathway, reduction of fibroblast proliferation, and the improvement of collagen organization are effects of SA, which aid in attenuation of hypertrophic scar formation. Our findings support the suggestion for further studies in this regard in order to test the safety and efficacy of SA, which can have great potentials for use in antiscarring therapies. These findings provide a mechanistic rationale for the translational development of SA as a topical antiscarring therapy.