Iris germanica L. Rhizome-Derived Exosomes Ameliorated Dihydrotestosterone-Damaged Human Follicle Dermal Papilla Cells Through the Activation of Wnt/β-Catenin Pathway

Hair loss is often associated with oxidative stress and mitochondrial dysfunction in human follicle dermal papilla cells (HFDPCs), resulting in impaired cellular function and follicle degeneration. Thus, many studies have been conducted on natural plants aimed at inhibiting hair loss. This study investigated the therapeutic potential of exosomes derived from the rhizomes of <i>Iris germanica</i> L. (Iris-exosomes) in HFDPCs damaged by dihydrotestosterone (DHT). Iris-exosomes significantly reduced reactive oxygen species (ROS) levels, restoring mitochondrial membrane potential and ATP production, thereby mitigating oxidative stress and improving mitochondrial function. These effects occurred alongside enhanced cellular processes critical for hair follicle regeneration, including increased cell migration, alkaline phosphatase (ALP) activity, and three-dimensional (3D) spheroid formation, which replicates the follicle-like microenvironment and promotes inductive potential. Furthermore, Iris-exosomes stimulated the Wnt/β-catenin signaling pathway by enhancing glycogen synthase kinase-3β (GSK-3β), AKT, and extracellular signal-regulated kinase (ERK), leading to β-catenin stabilization and nuclear translocation, thereby supporting the expression of genes essential for hair growth. Taken together, these findings suggest that Iris-exosomes can be promising ingredients for alleviating hair loss.