Hypericin and berberine promote elongation of hair peg-like sprouting in hair follicle organoids via oxytocin signaling activation.

Oxytocin is a hormone produced during childbirth and lactation. Moreover, it is expressed in both men and women during physical contact with family members and pets. Oxytocin influences various organs and tissues, including the heart, digestive system, and reproductive organs. We recently demonstrated that oxytocin acts on hair follicles to promote hair growth. However, owing to its large molecular weight and poor skin permeability, small-molecule alternatives are required for its practical application as a hair growth-promoting agent. In this study, we comprehensively investigated molecules that increase oxytocin receptor expression and those that act as receptor agonists to identify compounds with oxytocin-like activity. Using in vitro 2D culture of dermal papilla cells and in silico screening based on binding affinity for the oxytocin receptor, we identified hypericin as a compound that enhances oxytocin receptor expression and berberine as an oxytocin receptor agonist. The additive effects of hypericin and berberine on hair growth promotion were further demonstrated using hair follicle organoid-based assays. These findings highlight the potential of hypericin and berberine to act as small-molecule alternatives to oxytocin and should contribute to the development of novel therapeutic strategies for hair-loss diseases such as alopecia.