Kaempferol stimulates dermal papilla cells and upregulates Wnt/β-catenin signaling pathway for androgenetic alopecia treatment.

Androgenetic alopecia (AGA) is the most common form of progressive hair loss, marked by a multifaceted pathogenesis and a lack of effective pharmacological treatments to arrest its progression. Flavonoids have drawn considerable research attention for their potential in fostering hair regeneration, yet kaempferol (Kae), a well-researched flavone, remains unexplored as a therapeutic agent for AGA. This study delves into the mechanisms and efficacy of Kae in AGA treatment, employing a blend of in vivo and in vitro experiments, complemented by transcriptome sequencing and molecular docking techniques. In vitro, Kae exhibited no significant toxicity to dermal papilla cells (DPCs); instead, it enhanced DPCs proliferation and migration in a dose-dependent manner, and significantly mitigated dihydrotestosterone (DHT)-induced cellular damage. Transcriptomic analysis and RT-qPCR indicated that Kae modulates the Wnt/β-catenin signaling pathway. Molecular docking studies indicated that Kae has binding potential to β-catenin and Cyclin D1, pivotal proteins within this pathway. Subsequent immunofluorescence experiments and Western blot confirmed Kae's ability to promote β-catenin nuclear translocation and inhibit DHT-induced downregulation of β-catenin and Cyclin D1. In vivo, oral Kae administration substantially promoted hair regeneration in an AGA mouse model, with efficacy on par with oral finasteride. In conclusion, this study presents robust evidence that Kae effectively stimulates hair growth by bolstering DPCs function and counteracting DHT-induced damage, thus holding promising therapeutic potential for AGA sufferers.