Fermented Yeast Complex Extract Promotes Hair Regrowth by Decreasing Oxidative Stress

Hair growth is orchestrated by a complex cycle comprising the anagen, catagen, telogen, and exogen phases that are largely regulated by dermal papilla cells (DPCs). The disruption of oxidative balance and inflammation impairs follicle function and regeneration. Fermented yeast complex extract (FYCE) is a bioactive material derived from enzymatically hydrolyzed yeast and collagen substrates through a two-step fermentation with <i>Lactobacillus brevis</i> and <i>Lactobacillus plantarum</i>, enriched in antioxidant amino acids such as γ-aminobutyric acid (GABA) and L-alanine. In this study, we evaluated the effect of FYCE on hair regrowth, with a focus on its modulation of oxidative stress and inflammatory pathways in hydrogen peroxide (H₂O₂)-treated DPCs. FYCE treatment significantly enhanced NRF2 expression (3.2-fold compared to H₂O₂-treated DPCs), a central transcription factor controlling antioxidant defense, and concomitantly suppressed NF-κB activity (0.6-fold compared to H₂O₂-treated DPCs), a key mediator of inflammation. Importantly, FYCE also attenuated the activation of the NLRP3 inflammasome, as evidenced by the decreased expression levels of its molecular components. Complementary studies showed that FYCE increased IGF-1 (5.4-fold compared to H₂O₂-treated DPCs), Wnt10b (1.8-fold compared to H₂O₂-treated DPCs), and Wnt3a (2.9-fold compared to H₂O₂-treated DPCs), and stabilized β-catenin (2.8-fold compared to H₂O₂-treated DPCs). FYCE also showed these changes in the shaved animal skin, which was associated with increased hair follicle number (1.6-fold compared to the water-administered control group) and the anagen phase (3.0-fold compared to the water-administered control group). Collectively, our results suggest that FYCE promotes hair regrowth through the dual modulation of antioxidative and anti-inflammatory pathways, specifically by activating NRF2, inhibiting NF-κB signaling, and downregulating the NLRP3 inflammasome. These findings support FYCE as a promising candidate for further investigation as a treatment to prevent or reverse hair loss, with in vivo and clinical studies substantiating its efficacy and safety.