Teicoplanin alleviates androgenetic alopecia through inhibition of androgen receptor expression and enhancing dermal papilla cell proliferation.

Androgenetic alopecia (AGA) is a prevalent form of hair loss primarily driven by androgen receptor (AR) signaling. Currently, therapeutic options for AGA are limited. In this study, we conducted structure-based virtual screening of 3014 known compounds and identified teicoplanin, a glycopeptide antibiotic, as having potent binding affinity for the AR ligand-binding domain along with inhibition of protein expression. To investigate the potential therapeutic effects of teicoplanin on AGA, we performed both in vitro and in vivo experiments. In vitro, treatment with teicoplanin resulted in dose-dependent enhancement of human dermal papilla cell proliferation, while AR protein levels decreased. Additionally, dihydrotestosterone (DHT) induced AGA mice were treated with teicoplanin (5 mg/kg low dose and 10 mg/kg high dose) or vehicle as a control for 17 days. Results showed that subcutaneous administration of teicoplanin significantly improved hair regrowth in high dose group (average coverage: 52.3% ± 8.8% in the teicoplanin high dose group vs. 10.5% ± 3.6% in AGA group). Furthermore, hair follicles in the teicoplanin-treated group were notably larger than those in the AGA group. Immunofluorescent analysis revealed that teicoplanin treatment significantly increased Ki-67 staining, a marker of cellular proliferation, while reducing AR staining intensity. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting analyses demonstrated that teicoplanin downregulated AR and its downstream target gene, transmembrane protease serine 2, by 66% and 35%, while promoting AR ubiquitination and proteasomal degradation. Concurrently, teicoplanin enhanced β-catenin expression and upregulated vascular endothelial growth factor-A mRNA. Our findings suggest that teicoplanin may serve as a promising candidate for the treatment of AGA.