Exploring the Potential Molecular Mechanism of Sijunzi Decoction in the Treatment of Non-Segmental Vitiligo Based on Network Pharmacology and Molecular Docking.

Abstract

Non-segmental vitiligo is a common decolorized skin disease. The purpose of this study was to reveal the active components of Sijunzi decoction (SJZD) and the target genes for the treatment of non-segmental vitiligo. Based on TCMSP and GEO databases, effective components and targets of SJZD in the treatment of non-segmental vitiligo were revealed by network pharmacology. GO and KEGG were used to analyze the biological functions of SJZD targets. The Cytoscape-cytoHubba plugin was used to identify hub target genes. SsGSEA method was used to analyze the infiltration level of immune cells in non-segmental vitiligo. Molecular docking was performed to predict the interaction between active compounds and hub target genes. Finally, real-time PCR detection was also performed. It was found that 104 active compounds may be effective ingredients in the treatment of non-segmental vitiligo. These 104 compounds acted on 42 differentially expressed target genes. KEGG analysis showed that target genes were significantly enriched in immune-related pathways such as MAPK and TNF signaling pathways. A total of 6 hub target genes (AKT1, CASP3, PPARG, SIRT1, TNF and TP53) were identified using the Cytoscape-cytoHubba plugin. Molecular docking showed that active compounds quercetin, kaempferol, formononetin and naringenin had good binding to hub target genes. We also found that Type 2 T helper cells, CD56bright natural killer cell and CD56dim natural killer cell infiltration levels were abnormal in non-segmental vitiligo and correlated with AKT1. The results of this study indicate that quercetin, kaempferol, formononetin and naringenin in SJZD may play an important role in the treatment of non-segmental vitiligo by acting on AKT1, CASP3, PPARG, SIRT1, TNF and TP53 to regulate immune cell infiltration and multiple signaling pathways.