Treatment With Ashwagandha‐Derived Exosome‐Like Nanovesicles Up‐Regulates VEGF ‐A Production and Promotes Human Hair Growth Ex Vivo

Human-derived exosomes show promise for hair loss treatment but may pose safety concerns, including inflammatory responses and pathogen transmission. Here, we investigated whether plant-derived exosomes, whose isolation can be standardized, and which show lower compositional complexity and no immunogenicity, represent a valid alternative. We isolated and characterized exosome-like nanovesicles from the Ashwagandha plant (Ash-ELNs), which is traditionally used to relieve stress, and pre-clinically explored their hair growth-promoting potential. Multi-omic approaches demonstrated low variations in the content of seven different Ash-ELN preparations, and cellular vesicle uptake was confirmed in human dermal fibroblasts (HDFs). In a scratch assay of human dermal papilla fibroblasts (HDPCs), Ash-ELNs significantly increased the production/secretion of the hair growth promoters VEGF-A, PLGF1, FGF2 and LIF. Application of Ash-ELNs to healthy human microdissected hair follicles significantly prolonged anagen and increased hair shaft production, while hair matrix keratinocyte proliferation and -apoptosis remained unaltered. Ash-ELNs significantly upregulated VEGF-A protein expression in the bulb mesenchyme, corroborating our in vitro results. Finally, Ash-ELNs promoted tubulogenesis in an HDF-human umbilical vein endothelial cell (HUVEC) assay, suggesting VEGF-A-induced angiogenesis as a possible mechanism underlying the anagen promoting effect of Ash-ELN. Thus, Ash-ELN treatment offers a novel adjuvant strategy or non-drug agent to reduce hair shedding.