Understanding the ultrastructural aspects of berberine-induced skin-darkening activity in the toad, Bufo melanostictus, melanophores

has been done after treatment with various concentrations of berberine, along with specific antagonists and agonists of β-adrenoceptors in order to explore the mechanism of action of berberine-induced skin darkening. The results showed that the number of melanophores with melanin-loaded dendrites increased in the subepidermal layer significantly in berberine-treated skin pieces in a dose-dependent manner leading to skin darkening. Highly electron-dense melanosomes of Stage IV increased considerably due to the enhanced process of melanization. These effects were found to be antagonized by propranolol, and were also found to be highly potentiated by isoprenaline, which is a specific β-adrenoceptor agonist. The findings show that berberine possesses a skin-darkening potential and could be used as a safe melanogenic agent for the treatment of hypopigmentation disorders or vitiligo.