Hair follicle stem cells (HFSCs) are vital for maintaining hair growth and regeneration. Their dysfunction, often caused by oxidative stress or metabolic imbalance, leads to hair loss and scalp aging. β-catenin is a key protein in the Wnt signaling pathway, and its activity is crucial for HFSC maintenance and regeneration. In this study, we show that methylene blue (MB), a mitochondrial-targeted antioxidant, promotes HFSC proliferation and viability by both reducing reactive oxygen species (ROS) and activating the β-catenin signaling pathway. Functional tests demonstrated that MB significantly sped up wound healing in HFSC cultures, indicating enhanced regenerative ability. Although co-treatment with antioxidants like vitamins A and C improved ROS scavenging, it surprisingly reduced MB-induced β-catenin activation. Conversely, minoxidil, a clinically approved hair growth stimulant, synergized with MB to further activate β-catenin signaling and enhance HFSC viability. Lastly, exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) resulted in a dose-dependent decrease in HFSC survival, consistent with emerging reports of treatment-related hair loss. Remarkably, pre-treatment with MB protected HFSCs from GLP-1 RA-induced metabolic stress and premature cell death. Overall, these findings identify methylene blue as a multifunctional therapeutic candidate that reduces oxidative and metabolic stress while supporting HFSC-mediated hair regeneration.
Sadashivaiah et al. (Thu,) studied this question.