Anti-androgenetic effect of diphlorethohydroxycarmalol on testosterone-induced hair loss by inhibiting 5α-reductase and promoting Wnt/β-catenin signaling pathway in human dermal papilla cells.

Diphlorethohydroxycarmalol (DPHC), a marine phlorotannin compound derived from the brown alga Ishige okamurae, has been known to have a variety of biological effects. Recently, marine resources have been highlighted by their effects on ameliorating alopecia and related hair loss. Therefore, this study aimed to investigate the potential of DPHC isolated from I. okamurae as a hair loss treatment through examination of its anti-androgenic alopecia effects. Molecular docking analysis predicted that DPHC can be used as a 5α-reductase inhibitor superior to finasteride, which has traditionally been used as an anti-androgenic alopecia agent. In addition, DPHC significantly inhibited 5α-reductase activity in dihydrotestosterone (DHT)-treated human dermal papilla (HDP) cells, and downregulated hair growth inhibitor proteins such as AR, DKK1, TGF-β1, and IL-6. Moreover, DPHC treatment remarkably upregulated both the phosphorylation levels of GSK3β and expression levels of β-catenin in DHT-treated HDP cells, confirming the effects of DPHC on activating the Wnt/β-catenin signaling pathway. Therefore, these findings suggest that DPHC has a significant potential to prevent androgenic alopecia by promoting hair growth and preventing hair loss.