[Unveiling the mechanisms of baicalein in regulating allergic contact dermatitis: A network pharmacology approach]

Objective To elucidate the potential molecular mechanism of baicalein in the treatment of allergic contact dermatitis (ACD). Methods An in vitro inflammatory model was established using human keratinocytes (HaCaT cells) stimulated with tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ). The regulatory effect of baicalein on inflammatory factors was detected by quantitative real time polymerase chain reaction. Network pharmacology was applied to screen the common targets of baicalein and ACD. Key signaling pathways were predicted via a protein protein interaction (PPI) network and pathway enrichment analysis, and the binding capacity of baicalein to core targets was evaluated by molecular docking. Results In vitro experiments showed that baicalein significantly reduced the expression of pro-inflammatory factors in HaCaT cells induced by TNF-α combined with IFN-γ, but had no significant effect on the T helper 1 (Th1)/T helper 17(Th17)cell imbalance, suggesting that its anti inflammatory mechanism was not completely dependent on inflammatory pathways such as T cell activation and Th17 differentiation. A total of 46 potential targets of baicalein for ACD were screened by network pharmacology, and the functional enrichment was associated with inflammatory pathways including T cell activation and Th17 differentiation. Furthermore, 11 core targets were obtained from the 46 potential targets using CytoHubba and MCODE algorithms. Molecular docking results demonstrated that baicalein exhibited high binding affinity to core targets related to the cytochrome P450 (CYP450) family, among which the affinity with CYP1A1 was the highest (binding energy=-10.17 kcal.mol^-1, RMSD=1.14 ). Conclusion Baicalein exhibits significant therapeutic potential against ACD. It can downregulate the expression of inflammatory factors in HaCaT cells induced by TNF-α combined with IFN-γ, and its mechanism may be related to the interactions with CYP450 family-related targets.