Kaempferol enhances hair growth by regulating JAK3/STAT6 and TGF-β/Smad signaling in human dermal papilla cells and a C57BL/6 mousemodel

Kaempferol, a naturally occurring flavonoid found in hair growth-promoting plants, was investigated for its direct effects on hair loss prevention. This study assessed its impact on human dermal papilla (HDP) cells, essential regulators of hair follicle activity. Kaempferol significantly enhanced HDP cell proliferation in a dose-dependent manner, exceeding the effect of minoxidil. It markedly inhibited TGF-β1-induced Smad-binding activity (65.8%) and IL-4-induced STAT6 activity (72.5%), compared to finasteride (35%) and tofacitinib (96%), respectively. Western blot analysis showed suppression of phosphorylated Smad2/3 and STAT6, along with upregulation of CDK2, CDK4, cyclin D3, ERK1/2, IGF-1R, and VEGFR-2. In vivo, topical application of Kaempferol in C57BL/6 mice significantly promoted hair growth, increased follicle numbers, and improved hair thickness. These findings suggest that Kaempferol enhances hair growth through modulation of TGF-β/Smad and JAK3/STAT6 pathways and may serve as a promising natural therapeutic agent for hair loss treatment.