Pungenin Promotes Hair Growth in Mouse Models of Androgenic Alopecia Through Transcriptional Regulation of the PI3K/AKT/mTOR Axis

Androgenetic alopecia (AGA) is the most common form of hair loss, characterized by the progressive miniaturization of hair follicles driven by dihydrotestosterone (DHT)-mediated androgen receptor signaling. Current pharmacotherapies remain limited in efficacy and are often associated with undesirable side effects. Pungenin, a phenolic glucoside isolated from Picea wilsonii Mast., was investigated for its therapeutic efficacy in DHT-induced AGA model mice in this study. In primary mouse hair follicle cells exposed to DHT, pungenin mitigated cellular injury, restored normal morphology and viability, and significantly reduced the expression of type II 5α-reductase (Srd5α2). Topical treatment with pungenin markedly accelerated hair regeneration, as demonstrated by histological analysis and serum biochemical measurements. Transcriptomic profiling combined with network pharmacology suggested that the protective effects of pungenin are associated with transcriptional regulation of the PI3K/AKT/FoxO/mTOR axis, identifying 25 putative therapeutic targets, with qPCR further confirming the altered expression of key genes within this network. Collectively, these findings demonstrate that pungenin protects hair follicles against DHT-induced injury through suppression of Srd5α2 and transcriptional modulation of the PI3K/AKT/mTOR signaling axis, supporting further preclinical evaluation of pungenin as a potential candidate for AGA management.