Abstract
PURPOSE: Margarita (pearl) has detoxifying and skin barrier-repairing properties. The study was to evaluate the therapeutic effect of pearl on melasma and to preliminarily explore its possible mechanism of action. METHODS: The efficacy of pearl on patients with melasma was evaluated by the melasma area and severity index (MASI) and physician's global assessment (PGA) score. DNA sequencing was performed on pharyngeal swab samples from patients with melasma to obtain gene loci related to melasma. The active compounds and potential targets for pearl were retrieved from Integrated Traditional Chinese Medicine and HERB databases. The relevant genes of melasma were obtained from the GeneCards database and intersected with the targets of pearl to identify potential targets of pearl against melasma. The potential targets were mapped for the KEGG pathway in the KEGG Mapper and verified using human melanoma A375 cells that were exposed to ultraviolet irradiation. RESULTS: Pearl significantly improved the MASI and PGA scores of patients with melasma. DNA sequencing revealed that TYR and DCT were genes related to melasma. Calcium carbonate, iron, magnesium, manganese, silicon, strontium, and zinc were active compounds for pearl. CAMP-responsive element binding protein 1 (CREB1) was the target of pearl against melasma. Pearl regulated microphthalmia-associated transcription factors through CREB and affected melasma-related genes TYR and DCT, which in turn inhibit melanoma cell activity and intracellular tyrosinase activity. CONCLUSION: Pearl can alleviate melasma by targeting the CREB1/MITF axis and then the melasma-related gene loci TYR and DCT.