Therapeutic potential of Ishophloroglucin a from Ishige okamurae in androgenic alopecia: inhibition of 5α-reductase activity and activation of the Wnt/β-catenin signaling pathway in human dermal papilla cells

Abstract

Androgenic alopecia (AGA) is a common condition of hair loss, triggered by excessive 5 alpha-dihydrotestosterone (5 alpha-DHT) generated via 5 alpha-reductase activity. This study investigated the anti-alopecia effects of Ishophloroglucin A (IPA), a compound isolated from the brown seaweed Ishige okamurae. Molecular docking analysis revealed that IPA exhibits higher binding affinity to 5 alpha-reductase than finasteride. In human dermal papilla cells (HDPCs), IPA inhibited both 5 alpha-reductase activity and androgen receptor (AR) expression, reduced levels of dickkopf-related protein 1 (DKK1), transforming growth factor beta 1 (TGF-beta 1), and interleukin-6 (IL-6), and activated the Wnt/beta-catenin signaling pathway by promoting glycogen synthase kinase-3 beta (GSK3 beta) phosphorylation and upregulating beta-catenin (beta-catenin) expression. Additionally, IPA increased the expression of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF), both of which are associated with hair growth promotion. These findings suggest that IPA is a promising therapeutic candidate for treating AGA.