The aim of this research was to find a novel combination of compounds to effectively treat skin hyperpigmentation conditions such as melasma. Melasma has a complex pathophysiology with different cell types and signaling pathways involved. Paracrine factors secreted by keratinocytes but also fibroblasts and endothelial cells act on melanocytes and stimulate melanogenesis by modulating several pathways including WNT, EDN1, αMSH and SCF. Oxidative stress and inflammation also participate to the regulation of pigmentation. The aim of this study was to use artificial intelligence to screen for the best combination of ingredients for a depigmenting topical formula which can target the main melanogenic pathways. 12 compounds with proven depigmenting efficacy were analyzed using Artificial Neural Networks (ANNs)-based approach. This algorithm generates a model that simulates the skin pigmentation process considering all the molecular information available from reliable scientific databases, and gives the best combinations of depigmenting compounds. The proposed combination of actives (Retinol, Diosmin, Ferulic acid) was further tested in vitro to assess the synergistic effect in tyrosinase activity extracted from melanocytes and to evaluate the inhibition of the key pathways regulating melanogenesis through the quantification of specific markers by qPCR. The proposed combination of compounds by AI had a synergistic effect in vitro, as the inhibition of tyrosinase from melanocytes treated with all the compounds was 2.5x higher than the inhibition of tyrosinase after the treatment of each compound separated and added successively. The combination reduced by 35% the levels of COX-2, 85% the levels of ET-1 and induced by 90% the levels of the depigmenting cytokine IL-1β in fibroblasts. The combination also inhibited the dendricity stimulation in melanocytes by IBMX, an activator of the αMSH pathway.

ESDR541 - Novel synergistic combination of active ingredients for melasma topical therapy

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.