Polyphenols from Bacopa procumbens Nanostructured with Gold Nanoparticles Stimulate Hair Growth Through Apoptosis Modulation in C57BL/6 Mice.

Background/Objectives: Alopecia is a hair disorder with a significant impact on quality of life, and its incidence has been increasing in recent years. Current therapeutic options are limited and may cause adverse side effects, highlighting the need to develop safer and more effective formulations. Therefore, the objective of this study was to evaluate the effect of a formulation based on the bioactive fraction of Bacopa procumbens (BFNB), conjugated with gold nanoparticles, on hair growth through the modulation of apoptosis in C57BL/6 mice. Methods: The potential biological activities of the secondary metabolites of B. procumbens present in BFNB were analyzed in silico. In vivo experiments evaluated the expression of pro-apoptotic markers p53, caspase 3-p11, caspase 9-p10, and Bax, as well as anti-apoptotic marker Bcl-2, through Western blotting. Immunohistochemistry further assessed the expression and localization of some of these markers. Additionally, molecular docking and interactomic analyses were performed, complemented by functional enrichment, to explore molecular pathways modulated by the evaluated proteins. Results: In silico analyses suggested that BFNB metabolites are involved in the modulation of hair growth, hair fragility, and apoptosis. This finding was supported by in vivo experiments in mice, where BFNB significantly decreased the expression of p53, caspase 3-p11, caspase 9-p10, and Bax while increasing Bcl-2 levels. Immunohistochemistry showcased a reduction in pro-apoptotic markers in dermal and follicular bulb cells. Furthermore, molecular docking studies identified BFNB metabolites as potential direct modulators of these key proteins, strengthening evidence of their role in apoptotic regulation. The interactomic analysis highlighted 50 proteins associated with apoptosis, and functional enrichment underscored key processes such as p53 signaling, regulation of the apoptosome, and mitochondrial membrane involvement in the intrinsic apoptosis mechanism, among other pathways. Conclusions: This study demonstrates that BFNB effectively modulates apoptosis through key molecular mechanisms, highlighting its potential as an innovative therapy for promoting hair growth.