EGCG-Biotin-Pal-GHK composition modulates TGF-β and BMP pathways in scalp microenvironment for treating stress-induced alopecia.

Chronic stress commonly precipitates telogen effluvium (TE), but sustained stress can further induce follicular miniaturization and fibrosis. Thus, stress-induced alopecia may be considered a pathological continuum that progresses from TE to fibrotic follicular degeneration. Stress-induced alopecia involves multiple pathological mechanisms including follicular fibrosis, miniaturization and hair thinning. Currently, there is a lack of systematic therapeutic approaches targeting its multi-target pathological processes. This study proposes a novel combination strategy (EBP: EGCG, Biotin and Pal-GHK) designed to synergistically modulate the TGF-β/Smad and BMP signaling pathways to target key pathological processes in stress-induced alopecia. Through molecular docking, cell co-culture experiments, animal models and microbial interaction analysis, the EBP combination was systematically evaluated for its effects in inhibiting follicular fibrosis, promoting follicular regeneration and enhancing keratin synthesis. The results demonstrated that EBP effectively inhibited TGF-β/Smad pathway and activated BMP pathway. In the stress-induced fibrotic alopecia mouse model, compared to the Model group, the High EBP group significantly upregulated BMP2 by 2.77-fold, while downregulating TGF-β1 and P-Smad2 expression levels to 35.7% and 65.9%, respectively. These molecular changes were accompanied by substantial improvements in hair follicle morphology, hair shaft quality and hair regrowth. Furthermore, microbial biotransformation of EBP components may contribute to prolonged biological activity and sustained therapeutic efficacy. This study provides novel theoretical and experimental evidence for multi-target combined therapy in stress-induced alopecia.