%0 Journal Article %T Ellagic acid inhibits dihydrotestosterone-induced ferroptosis and promotes hair regeneration by activating the wnt/β-catenin signaling pathway. %A Fu H %A Li W %A Liu J %A Tang Q %A Weng Z %A Zhu L %A Ding B %J J Ethnopharmacol %V 330 %N 0 %D 2024 Aug 10 %M 38685364 %F 5.195 %R 10.1016/j.jep.2024.118227 %X BACKGROUND: Androgenic alopecia (AGA) is the most prevalent form of hair loss in clinical practice and affects the physical and psychological well-being of adolescents. Paeonia lactiflora Pallas (PL), which is widely used in traditional Chinese medicine, enhances blood function and promotes hair growth, and ellagic acid (EA), a polyphenol in PL extract, shows strong antioxidant, anti-aging, and anti-inflammatory properties and also plays a role in the treatment of various skin conditions. However, its role and mechanism of action in AGA remain unclear.
OBJECTIVE: To determine whether EA can rescue slow hair regeneration by regulating dihydrotestosterone (DHT)-induced ferroptosis in AGA mice and clarify the effect of EA on DHT-induced ferroptosis in dermal papilla cells (DPCs).
METHODS: Male C57BL/6 mice were used to establish a DHT-induced AGA mouse model, whereas DPCs were used to establish a DHT-induced cellular model. Thereafter, we investigated the therapeutic mechanism of action of EA via immunofluorescence, western blot analysis, immunohistochemistry, electron microscopy, and molecular docking.
RESULTS: EA stimulated hair regeneration in mice and reversed DHT-induced increases in iron content, lipid peroxidation, and DHT-induced mitochondrial dysfunction by activating the Wnt/β-catenin signaling pathway. Further, β-catenin knockdown suppressed the inhibitory effect of EA on DHT-induced ferroptosis in DPCs.
CONCLUSIONS: EA inhibits DHT-induced ferroptosis and promotes hair regrowth in mice by activating the Wnt/β-catenin signaling pathway. Thus, it has potential for use as a treatment option for AGA.