Mechanism of baicalein from Wudang Mountain <i>Scutellaria baicalensis</i> Georgi. against atopic dermatitis based on network pharmacology, transcriptomics and <i>in vitro</i> experimental validation

This study aims to explore the therapeutic mechanisms of baicalein, a flavonoid from Wudang Mountain <i>Scutellaria baicalensis</i> Georgi., in treating atopic dermatitis (AD) using a combination of network pharmacology, transcriptomics, molecular docking, and <i>in vitro</i> experiments. Based on the UPLC-MS/MS analysis, 271 compounds including 10 categories were identified, with flavonoids (62.36%) being the most abundant. Network pharmacology revealed 21 intersection targets between baicalein and AD, and PPI network analysis identified 10 hub genes, including MMP9, MAPK3, EGFR, TLR4, etc. Skin RNA-sequencing from normal and AD mice confirmed 9 of the 21 common targets, and KEGG enrichment analysis highlighted HIF-1α signalling pathway as the key mechanism. <i>In silico</i> molecular docking proved that baicalein has strong binding affinity with TLR4, EGFR, and VEGFA, which were the core targets enriched in HIF-1α signalling pathway. Additionally, <i>in vitro</i> cell experiments demonstrated that baicalein significantly down-regulated the protein expression levels of HIF-1α, TLR4, VEGFA.