Ferulic acid promotes hair growth via estrogen receptor alpha activation in cultured human dermal papilla cells

Current alopecia treatments have side effects and limited efficacy, highlighting the need for better alternatives. Estrogen and estrogen receptor alpha (ERα)-targeting therapies have shown promise in addressing female-pattern hair loss, outperforming some conventional options. This study investigated the hair growth-promoting effects of Cnidium officinale extract (COE) and its active compound, ferulic acid (FA), focusing on their role in activating ERα. Using human dermal papilla cells (DPCs) and cultured human hair follicles, we assessed cell proliferation, mitochondrial function, gene expression, and protein levels including transcriptome analysis. Both COE and FA significantly enhanced DPCs proliferation and mitochondrial activity, and extended hair follicle length during the anagen (growth) phase. Transcriptomic comparisons between FA- and estrogen-treated cells revealed upregulation of genes involved in energy metabolism, particularly those related to ATP regeneration. FA also elevated c-JUN mRNA expression, indicating estrogen-like ERα activation, and increased the expression of MAPK pathway-associated proteins, along with key growth factors. Additionally, co-treatment with FA and NMN, a cellular activity regulator, enhanced mitochondrial activity in a concentration-dependent manner beyond NMN alone. These findings suggest that COE and FA stimulate hair growth by enhancing DPCs function, with FA’s ERα-activating properties offering potential as a novel therapeutic option for alopecia.