Identification of dihydrokaempferol from Platycladus orientalis leaves as a potential therapeutic candidate for androgenetic alopecia through modulation of the KIT-mediated mast cell axis

Background/objectives Androgenetic alopecia (AGA) is the most common form of hair loss, characterized by progressive follicular miniaturization. Current therapies mainly target androgen signaling and show limited efficacy. Emerging evidence indicates that immune dysregulation contributes to AGA progression, but its therapeutic implications remain unclear. This study aimed to identify active compounds from Platycladus orientalis leaves and investigate their mechanisms in regulating AGA. Methods AGA-related genes were identified through integrated analysis of public databases and transcriptomic data. Active compounds from Platycladus orientalis leaves were screened using TCMSP, BATMAN-TCM, GraphBAN prediction, and ADMET evaluation. Compound-target interactions were characterized by molecular docking and molecular dynamics simulations. Immune infiltration analysis was per-formed to identify AGA-associated immune alterations. Human hair follicle specimens and an SCF-induced mouse model were used for experimental validation. Results Dihydrokaempferol and Germacrene D were identified as key active compounds of Platycladus orientalis leaves. Integrated network analysis and molecular simulations revealed KIT as a potential target of dihydrokaempferol with strong binding stability. Immune profiling identified mast cells as a prominent dysregulated immune population in AGA, and increased mast cell infiltration was confirmed in balding hair follicles. In vivo , dihydrokaempferol alleviated SCF-induced hair growth inhibition and reduced mast cell infiltration and degranulation. Conclusions This study supports a possible dihydrokaempferol-KIT-mast-cell axis in AGA, but they do not establish direct binding to or inhibition of KIT. Dihydrokaempferol may modulate SCF/KIT-associated mast-cell activity and warrants direct biochemical validation.