ABSTRACT
Objective: Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Fructus Ligustri Lucidi (FLL) has been used for premature graying of hair since ancient China and is currently used to treat vitiligo. However, the key biomarkers and mechanisms underlying FLL in vitiligo remain unclear. This study aimed to identify the potential biomarkers and mechanisms of FLL in vitiligo using network pharmacology analysis. Methods: The expression profiles of GSE65127 and GSE75819 were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between the vitiligo and healthy samples. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs were performed using R analyses. We performed R to further understand the functions of the critical targets. Cytoscape tools have facilitated network topology analysis. Molecular docking was performed using Auto Dock Vina software. Results: The results showed that 13 DEGs were screened in vitiligo. Based on bioinformatics, network pharmacology and Western blot, we found that the critical targets of melanoma antigen recognized by 5,6-dihydroxyindole-2-carboxylic acid oxidase (TYRP1) may be related to the mechanism of action of FLL in the treatment of vitiligo. Conclusion: TYRP1, as a melanocyte molecular biomarker, may be closely related to the underlying mechanism of FLL in the treatment of vitiligo via the inhibition of melanocyte death.
ABSTRACT
Psychological stress triggers onset and development of vitiligo in humans. However, the mechanism of psychological stress on vitiligo remains unclear. The study aims to investigate whether psychological stress promotes vitiligo and explore the underlying mechanism. A depigmentation mouse model induced by applying a skin-bleaching reagent monobenzone to dorsal skin and an in vitro HaCaT keratinocyte death model induced by monobenzone were employed to explore the effect of restraint stress, which mimics psychological stress, on depigmentation. The results indicated that restraint stress promoted vitiligo-related depigmentation, vacuolisation, spongiosis, CD8+ T lymphocyte infiltration, and loss of melanocytes in the skin. Restraint stress activated cutaneous NLR family containing pyrin domain protein 3 (NLRP3) inflammasome. In addition, restraint stress aggravated anxiety-like behaviors and increased levels of macrophage migration inhibitory factor (MIF) and corticosterone in the circulation, accompanied with decreasing the expression of cutaneous 8-oxoguanine DNA glycosylase (OGG1) in depigmentation mice. In vitro experiments demonstrated that activation of glucocorticoid receptor (GR) by cortisol upregulated NLRP3 expression dependent on MIF, and directly decreased the transcription of OGG1. Blockade of MIF reversed the NLRP3 signal in restraint stress-induced depigmentation mice. In conclusion, restraint stress promotes vitiligo-related depigmentation in mice via the activation of GR/MIF signaling pathway. The findings provide a theoretical basis for prevention and treatments of vitiligo with therapies of targeting GR, MIF, and OGG1.
