Abstract
β‑sitosterol (SIT) has anti‑inflammatory, anti‑tumor and anti‑fibrotic effects. However, the precise mechanisms underlying its efficacy in keloid treatment remain elusive. The present study aimed to elucidate the therapeutic effect of SIT on keloids. The active components of Fructus arctii, target molecules of these components and disease‑associated target molecules were identified and retrieved from various databases. Molecular docking was employed to evaluate the binding affinity of the active compounds for key targets. Cell viability and proliferation were evaluated via CCK‑8 and EdU assays, while cell migration capacity was assessed via wound healing assays and cell migration and invasion abilities were determined via Transwell assays. A rescue study involving YS‑49 was conducted. Western blot analysis was performed to assess the expression levels of proteins associated with EMT and proteins involved in the PI3K/AKT signaling pathway. A subcutaneous keloid fibroproliferative model was established in nude mice and immunohistochemical staining was performed on tissue sections. By intersecting the keloid targets, 29 targets were identified, with 10 core targets revealed by protein-protein interaction analysis. Molecular docking revealed a robust binding affinity between SIT and PTEN. In addition to inhibiting cell viability, invasion and migration, SIT significantly decreased the levels of phosphorylated (p‑)PI3K and p‑AKT, downregulated the protein expression of Vimentin and Snail proteins and increased the protein expression of Zonula Occludens‑1 and E‑cadherin. YS‑49 reversed the inhibitory effect of SIT on keloid in SIT‑treated cells. In vivo experiments demonstrated that SIT suppressed the growth of a keloid model in nude mice and increased PTEN expression. The present study provided the first evidence that SIT inhibits keloid proliferation, migration and invasion by modulating the PTEN/PI3K/AKT signaling pathway, suggesting its potential as a novel therapeutic approach for keloid treatment.