Hemp Seed-Derived Exosomes Protect Against Dihydrotestosterone-Induced Hair Growth Inhibition

Background: Dihydrotestosterone (DHT), a potent androgen, suppresses key molecular pathways involved in hair follicle growth and contributes to alopecia. Hemp seed callus-derived exosomes (E40) demonstrated regenerative properties for cellular differentiation and immune regulation. This study investigated the protective effects of E40 against the DHT-induced inhibition of hair follicle development in a chicken embryo model. Methods: Chicken embryos at embryonic day 7 (E7) were injected with DHT (50 ng/mL) alone or in combination with E40 (40 µg/mL) and incubated until embryonic day 12 (E12). Feather length, density, and molecular marker expression were analyzed using fluorescence in situ hybridization and western blotting. Results: DHT exposure significantly reduced feather length and density in chicken embryos. However, the E40 treatment restored feather length and density to levels comparable to those of untreated controls. E40 also restored patched 1, sonic hedgehog, smoothened, and zinc finger protein GLI1 expression, which are crucial markers of the sonic hedgehog signaling pathway. Additionally, E40 suppressed bone morphogenetic protein 4 expression by approximately 30%, further promoting hair follicle growth. Conclusion: These results suggest that E40 effectively mitigates DHT-induced hair follicle damage by restoring key molecular pathways and suppressing alopecia-related markers. E40’s multi-faceted mechanism presents a promising therapeutic candidate for alopecia treatment and hair follicle regeneration strategies. Further studies are warranted to evaluate its efficacy in mammalian models and in clinical settings.