MitoQ enhances CYP19A1 expression to stimulate WNT/β-catenin signaling pathway for promoting hair growth in androgenetic alopecia

Increased sensitivity to androgens and androgen receptors is the underlying cause of androgenetic alopecia (AGA), a hereditary disease. Our study investigated the preventive effects of MitoQ on dihydrotestosterone (DHT)-induced mitochondrial dysfunction and subsequent hair loss from three perspectives: in vivo, in vitro, and network pharmacology. A mouse model of AGA was used to assess the effectiveness of MitoQ intervention. Seventy-five drug targets and 367 disease targets were identified through network pharmacology analysis. Molecular docking analysis revealed that the androgen receptor (AR) and CYP19A1, which are key targets of MitoQ, may play a role in AGA treatment. CYP19A1 expression was downregulated in lesions from patients with AGA compared to healthy scalp tissue, while AR expression was upregulated. Cellular tests of human dermal papilla cells (DPCs) treated with MitoQ revealed that the mRNA and protein expression of AR remained unchanged, but the mRNA expression of CYP19A1 was upregulated. Our experiments also confirmed that CYP19A1 overexpression prevented DHT-induced apoptosis and upregulated the expression levels of WNT3A and β-catenin, whereas increased apoptosis levels and the downregulation of WNT3A and β-catenin due to CYP19A1 knockdown were reduced by MitoQ. We verified that MitoQ enhanced hair growth in DHT-induced hair loss model mice and reversed DHT-induced apoptosis by enhancing the expression of CYP19A1 in DPCs and that MitoQ may act by mediating the WNT/β-catenin pathway. These findings indicate that MitoQ could be a promising intervention for AGA and that CYP19A1 may serve as a valuable therapeutic target for AGA.