Ethnopharmacological relevance: 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.
Aim of the study: 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).
Materials and 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.
Conclusion: 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.
Keywords: Androgenic alopecia; Dermal papilla cells; Ellagic acid; Ferroptosis; β-catenin.
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