Aloe Vera flowers extracts inhibit melanogenesis via activating PI3K/Akt signaling pathway: Network pharmacology and experimental validation

Aloe vera is a traditional herbal medicine that has been used for thousands of years. However, its flowers are commonly considered useless and discarded. Although, a few recent studies find Aloe vera flowers extracts (AVFE) with ability to inhibit tyrosinase (TYR) activity in vitro, systematic research on AVFE as skin whitening agent against melanogenesis in vitro and in vivo is yet lack. Therefore, the anti-TYR activity and anti-melanogenic effects of AVFEs in vitro B16F10 cell model and in vivo zebrafish embryo model, analysis of all-components of AVFE, network pharmacology and protein expression of melanogenesis-related signaling pathways were well conducted in this study. The results demonstrated that AVFE could significantly reduce cellular TYR activity and melanin content via activating the phosphorylation of p-Akt and p-GSK-3β in PI3K/Akt signaling pathway, followed by reducing the phosphorylation of MITF and then downregulation of TYR, TRP1 and TRP2 expression levels, and finally decreasing TYR, TRP1, TRP2 and melanin syntheses. In addition, 24 components of AVFE were most likely responsible for its skin depigmentation. In conclusion, this study provides a basis for understanding the mechanism of AVFE on skin depigmentation, as well as a potential for applying AVFE as skin whitening agent in cosmetics.