Bioinspired engineering of Polygonum multiflorum root nanovesicles regulates dermal papilla cells in vitro and stimulates human hair follicle growth ex vivo

Introduction Polygonum multiflorum (PM), a traditional medicinal herb, is renowned for its regenerative effects on hair growth; however, its therapeutic application has been largely confined to crude extracts. Recent advances have highlighted plant-derived nanovesicles (PDNVs) as natural carriers of bioactive molecules. This study aimed to evaluate the hair growth–promoting potential of nanovesicles derived from the roots of Polygonum multiflorum (PM-NVs). Methods PM-NVs were isolated from fresh PM roots using differential and density gradient ultracentrifugation. Their morphology was confirmed by transmission electron microscopy. Human dermal papilla cells (DPCs) were treated with PM-NVs to assess proliferation using the CCK-8 assay and β-catenin activation via Western blot and quantitative RT-PCR (qRT-PCR). Ex vivo cultured human hair follicles (HFs) were treated with PM-NVs to evaluate hair shaft elongation. Results PM-NVs were spherical and efficiently internalized by DPCs. Treatment with PM-NVs significantly increased DPC proliferation in a dose-dependent manner, upregulated β-catenin protein levels, promoted its nuclear translocation, and enhanced the expression of downstream target genes ( Axin2, Lef1 , and EP2 ). Ex vivo , PM-NV treatment significantly enhanced human hair follicle elongation compared with controls, indicating stimulation of the hair growth phase. Conclusions PM-NVs derived from Polygonum multiflorum promote dermal papilla cell (DPC) proliferation and activate β-catenin signaling, resulting in enhanced hair shaft elongation ex vivo. These findings suggest that PM-NVs represent a natural, biocompatible nanovesicle-based approach for hair follicle regeneration and hold potential as a therapeutic option for alopecia.