Dendrobium officinale polysaccharide improves hair regrowth in androgenetic alopecia mice and is associated with coordinated changes in local steroid metabolism, ESR1 activation, and keratin-related follicular responses

<h4>Background</h4>Androgenetic alopecia (AGA) is characterized by androgen-dependent follicular miniaturization and progressive disturbance of follicular structure and cycling. Local steroid metabolism, including 5α-reductase-related androgen production and aromatase-related estrogen conversion, may contribute to this process.<h4>Methods</h4>A dihydrotestosterone (DHT)-induced mouse model of AGA was used to evaluate the <i>in vivo</i> effects of <i>Dendrobium officinale</i> polysaccharide (DOP). Dose screening was followed by histological assessment, quantitative proteomics, biochemical assays, multiplex immunofluorescence, and pharmacological perturbation with 17α-estradiol (17α-E2) and letrozole (LETZ).<h4>Results</h4>DOP improved hair regrowth in a dose-related manner, and the high-dose group showed the most consistent changes in hair coverage, hair follicle density, dermal thickness, hair bulb diameter, and anagen proportion. Proteomic analysis served to narrow the candidate range and prioritize steroid hormone biosynthesis- and estrogen-signaling-related processes. Quantitative evaluation showed that DOP treatment was associated with lower SRD5A1 expression, higher CYP19A1 expression, lower local dihydrotestosterone and testosterone levels, increased p-ESR1, and increased KRT28/KRT71 expression. Spatial analysis further showed a shift of CYP19A1, ESR1, and KRT28 toward hair matrix- and inner root sheath-associated regions. Pharmacological modulation with 17α-E2 and LETZ altered these DOP-related changes, although not uniformly across all endpoints.<h4>Conclusion</h4>In this model, the <i>in vivo</i> response to DOP was associated with changes related to local steroid metabolism, ESR1 activation, and keratin-related follicular responses, together with improvement in follicular morphology and cycle status. These findings support a candidate response framework for further study of DOP in AGA.