Hair growth-promoting activity of ginsenoside Rf from Panax ginseng C.A. Meyer, an industrial crop-derived functional material

Panax ginseng is cultivated worldwide for traditional medicinal purposes and as an industrial crop with potential bio-based applications. Among the active metabolites in P. ginseng C.A. Meyer, ginsenoside Rf (G-Rf) is a unique saponin. In this study, we investigated the biological activity of G-Rf, focusing on its anti-androgenetic alopecia potential. In a dihydrotestosterone-treated mouse model, oral administration of G-Rf promoted hair regrowth and increased hair shaft thickness. The expression of hair growth-inhibitory genes, including dickkopf 1, bone morphogenetic protein 2, and interleukin-6, was markedly attenuated in the dorsal skin tissue of G-Rf-treated mice. Mechanistically, G-Rf enhanced androgen receptor (AR) ubiquitination and proteasomal degradation by binding to and inhibiting ubiquitin-specific peptidase 10 (USP10), a deubiquitinating enzyme that stabilizes AR without altering its expression in the testicular tissue or causing systemic toxicity. These findings highlight G-Rf as a natural metabolite derived from the industrial crop P. ginseng. G-Rf specifically targets AR signaling through USP10 inhibition and has strong potential as a functional ingredient for application in the cosmetic and functional food industries.