Abstract
Hair and nails serving protective roles differ in structure. Recent bioinformatics research has found that Wnt signaling is crucial for their growth. However, they show unique expression patterns of specific elements such as R-spondin, LGR receptors, and BMP. To identify small molecules that can enhance the Wnt/β-catenin pathway, assess their effects on RSPO, LGR, and BMP expression, and determine their influence on hair and nail growth. FDA-approved drugs and natural compounds (n = 5,170) were screened using HEK293 cells with TCF/LEF luciferase gene by measuring luciferase activity and cell viability. Selected drugs were tested with human dermal papilla cells to observe Wnt signaling gene expression. Three top candidates were further tested with C57BL/6 mice for hair and nail growth effects. Nine drugs were identified as significant activators of Wnt signal and categorized into antivirals (Imidocarb, Proflavine, Aminoacridine), anticancer drugs (Entinostat, Tucidinostat, Enzastaurin, Abemaciclib), and GSK-3β inhibitors (CP21R7, BIO). RT-PCR revealed that Aminoacridine and Proflavine notably increased Wnt-related genes RSPO3 and RSPO4. Aminoacridine also significantly reduced the Wnt inhibitor WIF1 gene. In animal experiments, Aminoacridine, especially combined with Minoxidil, resulted in better hair growth than other drugs and Minoxidil alone. Imidocarb and Proflavine also significantly increased toenail length. Six new drugs were discovered, with Aminoacridine and Aminoacridine combined with Minoxidil showing high potential for hair and nail regeneration via the Wnt/β-catenin pathway, underscoring the need for extensive clinical trials to verify these drugs' safety and efficacy, offering hope for effective hair and nail loss treatments.